A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.
Bone loss due to osteoclastic activity.
A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.
A tumor necrosis factor receptor family member that is specific for RANK LIGAND and plays a role in bone homeostasis by regulating osteoclastogenesis. It is also expressed on DENDRITIC CELLS where it plays a role in regulating dendritic cell survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Excessive formation of dense trabecular bone leading to pathological fractures; OSTEITIS; SPLENOMEGALY with infarct; ANEMIA; and extramedullary hemopoiesis (HEMATOPOIESIS, EXTRAMEDULLARY).
An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2.
A secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis. It is a soluble decoy receptor of RANK LIGAND that inhibits both CELL DIFFERENTIATION and function of OSTEOCLASTS by inhibiting the interaction between RANK LIGAND and RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B.
A cysteine protease that is highly expressed in OSTEOCLASTS and plays an essential role in BONE RESORPTION as a potent EXTRACELLULAR MATRIX-degrading enzyme.
A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.
Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.
A mononuclear phagocyte colony-stimulating factor (M-CSF) synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (RECEPTOR, MACROPHAGE COLONY-STIMULATING FACTOR).
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The continuous turnover of BONE MATRIX and mineral that involves first an increase in BONE RESORPTION (osteoclastic activity) and later, reactive BONE FORMATION (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium HOMEOSTASIS. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as OSTEOPOROSIS.
Dissolution of bone that particularly involves the removal or loss of calcium.
The process of bone formation. Histogenesis of bone including ossification.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2.
Proton-translocating ATPases that are involved in acidification of a variety of intracellular compartments.
Glycoproteins found on the membrane or surface of cells.
Mature osteoblasts that have become embedded in the BONE MATRIX. They occupy a small cavity, called lacuna, in the matrix and are connected to adjacent osteocytes via protoplasmic projections called canaliculi.
Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents.
A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults.
The SKELETON of the HEAD including the FACIAL BONES and the bones enclosing the BRAIN.
The growth and development of bones from fetus to adult. It includes two principal mechanisms of bone growth: growth in length of long bones at the epiphyseal cartilages and growth in thickness by depositing new bone (OSTEOGENESIS) with the actions of OSTEOBLASTS and OSTEOCLASTS.
Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.
Transport proteins that carry specific substances in the blood or across cell membranes.
Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.
A receptor for MACROPHAGE COLONY-STIMULATING FACTOR encoded by the c-fms proto-oncogene (GENES, FMS). It contains an intrinsic protein-tyrosine kinase activity. When activated the receptor undergoes autophosphorylation, phosphorylation of down-stream signaling molecules and rapid down-regulation.
Tumors or cancer located in bone tissue or specific BONES.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS.
The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Diseases of BONES.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass. The resultant architecture of the bone assumes a mosaic pattern in which the fibers take on a haphazard pattern instead of the normal parallel symmetry.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.
A signal transducing tumor necrosis factor receptor associated factor that is involved in regulation of NF-KAPPA B signalling and activation of JNK MITOGEN-ACTIVATED PROTEIN KINASES.
X-RAY COMPUTERIZED TOMOGRAPHY with resolution in the micrometer range.
A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.
A negatively-charged extracellular matrix protein that plays a role in the regulation of BONE metabolism and a variety of other biological functions. Cell signaling by osteopontin may occur through a cell adhesion sequence that recognizes INTEGRIN ALPHA-V BETA-3.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
The longest and largest bone of the skeleton, it is situated between the hip and the knee.
The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption.
Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.
Parent cells in the lineage that gives rise to MONOCYTES and MACROPHAGES.
An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.
The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the FIBULA laterally, the TALUS distally, and the FEMUR proximally.
Receptors such as INTEGRIN ALPHAVBETA3 that bind VITRONECTIN with high affinity and play a role in cell migration. They also bind FIBRINOGEN; VON WILLEBRAND FACTOR; osteopontin; and THROMBOSPONDINS.
Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization.
Membrane-associated tyrosine-specific kinases encoded by the c-src genes. They have an important role in cellular growth control. Truncation of carboxy-terminal residues in pp60(c-src) leads to PP60(V-SRC) which has the ability to transform cells. This kinase pp60 c-src should not be confused with csk, also known as c-src kinase.
Cellular DNA-binding proteins encoded by the c-fos genes (GENES, FOS). They are involved in growth-related transcriptional control. c-fos combines with c-jun (PROTO-ONCOGENE PROTEINS C-JUN) to form a c-fos/c-jun heterodimer (TRANSCRIPTION FACTOR AP-1) that binds to the TRE (TPA-responsive element) in promoters of certain genes.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Established cell cultures that have the potential to propagate indefinitely.
A basic helix-loop-helix leucine zipper transcription factor that regulates the CELL DIFFERENTIATION and development of a variety of cell types including MELANOCYTES; OSTEOCLASTS; and RETINAL PIGMENT EPITHELIUM. Mutations in MITF protein have been associated with OSTEOPETROSIS and WAARDENBURG SYNDROME.
An abnormal hardening or increased density of bone tissue.
Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The hard portion of the tooth surrounding the pulp, covered by enamel on the crown and cementum on the root, which is harder and denser than bone but softer than enamel, and is thus readily abraded when left unprotected. (From Jablonski, Dictionary of Dentistry, 1992)
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
The surgical removal of one or both ovaries.
Tumors of bone tissue or synovial or other soft tissue characterized by the presence of giant cells. The most common are giant cell tumor of tendon sheath and GIANT CELL TUMOR OF BONE.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

Murine matrix metalloproteinase 9 gene. 5'-upstream region contains cis-acting elements for expression in osteoclasts and migrating keratinocytes in transgenic mice. (1/2998)

Knowledge about the regulation of cell lineage-specific expression of extracellular matrix metalloproteinases is limited. In the present work, the murine matrix metalloproteinase 9 (MMP-9) gene was shown to contain 13 exons, and the 2.8-kilobase pair upstream region was found to contain several common promoter elements including a TATA box-like motif, three GC boxes, four AP-1-like binding sites, an AP-2 site, and three PEA3 consensus sequences that may be important for basic activity of the gene. In order to identify cell-specific regulatory elements, constructs containing varying lengths of the upstream region in front of a LacZ reporter gene were made and studied for expression in transgenic mice generated by microinjection into fertilized oocytes. Analyses of the mice revealed that the presence of sequences between -2722 and -7745 allowed for expression in osteoclasts and migrating keratinocytes, i. e. cells that have been shown to normally express the enzyme in vivo. The results represent the first in vivo demonstration of the location of cell-specific control elements in a matrix metalloproteinase gene and show that element(s) regulating most cell-specific activities of 92-kDa type collagenase are located in the -2722 to -7745 base pair region.  (+info)

Granulocyte/macrophage colony-stimulating factor and interleukin-3 correct osteopetrosis in mice with osteopetrosis mutation. (2/2998)

Although young mice homozygous for the osteopetrosis (op) mutation usually developed prominent osteopetrosis, its severity was markedly reduced in aged op/op mice. This age-associated reversal of osteopetrosis was accompanied by the expansion of bone marrow cavities and increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive cells and of macrophages in the bone marrow. The TRAP-positive cells were mononuclear and developed ruffled borders and numerous vesicles, vacuoles, and granules. Enzyme-linked immunosorbent assay demonstrated a significant elevation of serum granulocyte/ macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 levels in the aged op/op mice. To examine whether GM-CSF and/or IL-3 could correct osteopetrosis in young op/op mice, 5 ng of recombinant murine (rm)GM-CSF and/or 100 ng of rmIL-3 were injected daily into young op/op mice. In these treated young op/op mice, the bone marrow cavities were expanded significantly at 2 weeks after administration, associated with significantly increased numbers of TRAP-positive cells and bone marrow macrophages. TRAP-positive cells increased in number with days after injection. These results suggest that GM-CSF and IL-3 induce the development of osteoclasts to correct osteopetrosis in the op/op mice with aging.  (+info)

Midpalatal suture of osteopetrotic (op/op) mice exhibits immature fusion. (3/2998)

The midpalatal suture was observed histologically in both toothless osteopetrotic (op/op) and normal (control) mice. The normal mice had a mature sutural structure, which consists of a well-developed cartilage cell zone and palatal bone. In contrast, the thickness of the cartilage cell zone was substantially greater in the op/op mice than that in the controls. Moreover, the cartilage cells in the op/op mice were frequently found in the palatal bone as well as in the sutural space, exhibiting an imperfect fusion. It seems that immature fusion at the sutural interface in the op/op mice is related to a decrease in biting or masticatory force accompanied by the failure of tooth eruption in addition to an essential defect in osteoclast differentiation, which is a congenital symptom in op/op mice.  (+info)

A novel role of IL-15 in the development of osteoclasts: inability to replace its activity with IL-2. (4/2998)

IL-15 shares many activities with IL-2 on stimulating lymphocytes, hematopoietic progenitor cells, and macrophages. However, the role of IL-15 in osteoclastogenesis has not been elucidated. The recent finding of abundant IL-15 in rheumatoid arthritis synovial fluids suggested a possible role for this cytokine in the pathological destruction of bone and prompted us to determine whether IL-15 stimulates osteoclast formation. IL-15 stimulated the formation of multinucleated osteoclast-like cells in rat bone marrow cultures. In stroma-free cultures, IL-15 increased the number of mononuclear preosteoclast-like cells in the early stage of osteoclast formation. The stimulation was observed even after treatment with IL-15 for only 24 or 48 h of culture. Moreover, low IL-15 concentration (0.1 ng/ml) strongly increased the level of calcitonin receptor mRNA of mononuclear preosteoclast-like cells. Although IL-15 is known as a potent stimulator of TNF-alpha, its activity was not abolished by addition of anti-TNF-alpha Ab. Interestingly, IL-2 and IL-7, which utilize some IL-15R components, had no effect on osteoclast differentiation, but pretreatment with IL-2 or IL-7 of bone marrow cells before the addition of IL-15 inhibited the enhancing activity of IL-15. In summary, IL-15 has a novel activity to stimulate the differentiation of osteoclast progenitors into preosteoclasts, which cannot be replaced by IL-2 but may use components in common with IL-2R to mediate its effects.  (+info)

Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. (5/2998)

A receptor that mediates osteoprotegerin ligand (OPGL)-induced osteoclast differentiation and activation has been identified via genomic analysis of a primary osteoclast precursor cell cDNA library and is identical to the tumor necrosis factor receptor (TNFR) family member RANK. The RANK mRNA was highly expressed by isolated bone marrow-derived osteoclast progenitors and by mature osteoclasts in vivo. Recombinant OPGL binds specifically to RANK expressed by transfected cell lines and purified osteoclast progenitors. Transgenic mice expressing a soluble RANK-Fc fusion protein have severe osteopetrosis because of a reduction in osteoclasts, similar to OPG transgenic mice. Recombinant RANK-Fc binds with high affinity to OPGL in vitro and blocks osteoclast differentiation and activation in vitro and in vivo. Furthermore, polyclonal Ab against the RANK extracellular domain promotes osteoclastogenesis in bone marrow cultures suggesting that RANK activation mediates the effects of OPGL on the osteoclast pathway. These data indicate that OPGL-induced osteoclastogenesis is directly mediated through RANK on osteoclast precursor cells.  (+info)

Morphological changes in periodontal mechanoreceptors of mouse maxillary incisors after the experimental induction of anterior crossbite: a light and electron microscopic observation using immunohistochemistry for PGP 9.5. (6/2998)

Ruffini nerve endings (mechanoreceptors) in the periodontal ligament (PDL) of mouse incisors were examined to elucidate whether experimentally-induced crossbites cause any changes or abnormalities in their morphology and distribution. Anterior guiding planes were attached to the mandibular incisors of 3-week-old C3H/HeSlc mice. At 3 days and 1, 2, 4, 6, and 8 weeks post-attachment of the appliance, the mice were sacrificed by perfusion fixation. Frozen sagittal cryostat sections of the decalcified maxillary incisors were processed for immunohistochemistry of protein gene product 9.5, followed by histochemical determination of tartrate-resistant acid phosphatase activity to reveal sites of alveolar bone resorption. Despite the absence of bone resorption within the lingual PDL of control mice, distinct resorption sites were seen in the respective regions of the experimental animals. Unlike the controls, many Ruffini endings showing vague and swollen contours, with unusually long and pedunculated micro-projections were observed in the affected lingual PDL of the incisors in the experimental animals with short-term anterior crossbite induction. Club-shaped nerve terminations with few, if any, micro-projections were observed in the lingual PDL of experimental animals with long-term induction, as well as in aged control mouse incisors. Differences in the distribution of Ruffini endings were also observed. These results indicate that changing the direction of the force applied to the PDL results in rapid and prolonged changes in the morphology of Ruffini-like mechanoreceptors.  (+info)

Study of the cell biology and biochemistry of cherubism. (7/2998)

AIMS: To establish whether the multinucleate cells in lesions of patients with cherubism are also osteoclasts and if this is the case whether they were responsive to calcitonin; to carry out cytogenetic studies on two members of the same family affected by cherubism in an attempt to identify any major chromosomal defects; and to perform an in-depth modern biochemical study of four children in the same family. SUBJECTS AND METHODS: Four related children with cherubism were studied. Tissue taken from one of the children at elective decompression of an optic nerve was submitted to in vitro bone resorption studies. Cytogenetic studies were done on two of the children and biochemical studies on all four. RESULTS: The multinucleate cells in the cherubic lesions were shown to be osteoclasts since they synthesised tartrate resistant acid phosphatase, expressed the vitronectin receptor, and resorbed bone. Bone resorption by the cultured multinucleate cells was significantly inhibited by calcitonin. High resolution cytogenetic studies failed to detect any chromosomal abnormalities in two children with cherubism. The biochemistry profile of all four children with cherubism showed that serum calcium, parathyroid hormone, parathyroid related hormone, calcitonin, and alkaline phosphatase were within normal levels. Urine analysis of pyridinium and deoxypyridinium cross links, hydroxyproline, and calcium in relation to urine creatinine were measured to assess bone resorption in these children, and the values were at the upper end of the normal range in all four. CONCLUSIONS: Further studies are required to determine whether calcitonin treatment will control this grossly deforming disease until the time when the physiological changes that occur at puberty rectify the pathology. It is not recommended that biochemical markers of bone resorption are used in isolation to monitor the activity of cherubism in individuals because the results are based on a small number of children and because of reports of marked interindividual variation in the levels of these markers, particularly in children.  (+info)

Promoter structure of mouse RANKL/TRANCE/OPGL/ODF gene. (8/2998)

Receptor activator of NF-kappa B ligand (RANKL)/tumor necrosis factor-related activation induced cytokine (TRANCE)/osteoprotegerin ligand (OPGL)/osteoclast differentiation factor (ODF) is a membrane-bound signal transducer responsible for differentiation and maintenance of osteoclasts. To elucidate the mechanism regulating RANKL/TRANCE/OPGL/ODF gene expression, we cloned the 5'-flanking basic promoter region of the mouse RANKL/TRANCE/OPGL/ODF gene and characterized it by transient transfection studies and genomic Southern blot analysis. Inverted TATA- and CAAT-boxes and a putative Cbfa1/Osf2/AML3 binding domain constituted the basic promoter structure. The repeated half-sites for the vitamin D3 (VitD3) and glucocorticoid receptors were located at -935 and -640, respectively. Transient transfection studies revealed that short-term treatment with 1alpha,25(OH)2 VitD3 or dexamethasone increased luciferase activity up to 204% and 178%, respectively; on the other hand, treatment with dibutyryl cyclic AMP did not affect the promoter activity. Since the expression of Cbfa1/Osf2/AML3 is also regulated by VitD3, 1alpha,25(OH)2 VitD3 might affect RANKL/TRANCE/OPGL/ODF gene expression both directly and indirectly. CpG methylation was observed dominantly in mouse stromal cells, ST2, of a later passage which ceased to support in vitro osteoclastogenesis, suggesting that the methylation status of the CpG loci in the RANKL/TRANCE/OPGL/ODF gene promoter may be one of the influential cis-regulating factors.  (+info)

Regulation of RANKL (receptor activator of nuclear factor κB ligand)-induced osteoclast differentiation is of current interest in the development of antiresorptive agents. Osteoclasts are multinucleated cells that play a crucial role in bone resorption. In this study, we investigated the effects of N-methylpyrrolidone (NMP) on the regulation of RANKL-induced osteoclastogenesis. NMP inhibited RANKL-induced tartrate-resistant acid phosphatase activity and the formation of tartrate-resistant acid phosphatase-positive multinucleated cells. The RANKL-induced expression of NFATc1 (nuclear factor of activated T cells, cytoplasmic 1) and c-Fos, which are key transcription factors for osteoclastogenesis, was also reduced by treatment with NMP. Furthermore, NMP induced disruption of the actin rings and decreased the mRNAs of cathepsin K and MMP-9 (matrix metalloproteinase-9), both involved in bone resorption. Taken together, these results suggest that NMP inhibits osteoclast differentiation and ...
TY - JOUR. T1 - IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release. AU - Kurihara, N.. AU - Bertolini, D.. AU - Suda, T.. AU - Akiyama, Y.. AU - Roodman, G. D.. PY - 1990/1/1. Y1 - 1990/1/1. N2 - IL-6 enhances the differentiation of pluripotent hematopoietic stem cells but predominantly affects the differentiation of hematopoietic cells in the granulocyte-macrophage lineage. We have previously shown that multinucleated cells (MNC) with many features of the osteoclast phenotype form in long term human marrow cultures. Addition of rhIL-6 (10 to 100 pg/ml) to these cultures significantly increased MNC formation, with , 80% of the MNC expressing an Ag that cross-reacts with the mAb 23c6. This antibody preferentially binds to osteoclasts. rhIL-6 did not enhance MNC formation in marrow cultures treated with 1,25 dihydroxyvitamin D3, a potent stimulator of MNC formation, but significantly increased the percentage of MNC that ...
TY - JOUR. T1 - Effects of stem cell factor on osteoclast-like cell formation in long-term human marrow cultures. AU - Demulder, A.. AU - Suggs, S. V.. AU - Zsebo, K. M.. AU - Scarcez, T.. AU - Roodman, G. David. PY - 1992/11. Y1 - 1992/11. N2 - Stem cell factor (SCF) is a newly described hematopoietic growth factor that stimulates the growth of primitive hematopoietic progenitors and mast cells. Since the osteoclast precursor is hematopoietic in origin, we tested SCF for its capacity to stimulate the formation of osteoclast-like multinucleated cells (MNC) in long-term human marrow cultures. These MNC express an osteoclast phenotype and form resorption lacunae on calcified matrices. Addition of SCF alone (0.1 pg/ml to 100 ng/ml) to long-term marrow cultures did not increase MNC formation. However, treatment of these cultures sequentially with SCF for 1 week followed by 1,25-(OH)2D3 for the second and third weeks of culture significantly enhanced MNC formation. [3H]Thymidine incorporation studies ...
Prostaglandin E2 (PGE2) is an important local regulator in bone. The present study was performed to investigate the effect of PGE2 on osteoclast-like cell formation and bone-resorbing activity of mature osteoclasts in the presence or absence of osteoblasts, PGE2 (10(-8) to 10(-6) M) significantly stimulated osteoclast-like cell formation in osteoblast-containing mouse bone cell cultures, although it did not affect osteoclast-like cell formation from hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor in osteoblast-free mouse spleen cell cultures. The conditioned medium from osteoblastic UMR-106 cells pretreated with PGE2 (10(-8) and 10(-6) M) significantly stimulated osteoclast-like cell formation from hemopoietic blast cells. PGE2 also significantly stimulated the bone-resorbing activity of mature osteoclasts in osteoblast-containing mouse bone cell cultures. In contrast, PGE2 significantly inhibited the bone-resorbing activity and osteopontin mRNA expression ...
Soy isoflavones and docosahexaenoic acid (DHA) are effective for maintaining bone health. This study investigated the combined effects of soy isoflavones and DHA on osteoclast formation. Mouse bone marrow cells were pre-cultured with macrophage colony-stimulating factor (M-CSF) for 3 days and then cultured with M-CSF and receptor activator of nuclear factor κB ligand (RANKL) for 6 days. RAW 264.7 cells were cultured with RANKL for 5 days. In mouse bone marrow cells, daidzein, genistein, and DHA significantly decreased the number of tartrate-resistant acid phosphatase-positive multinucleated cells (TRAP(+)MNCs), and the combination of soy isoflavones and DHA further decreased the number of TRAP(+)MNCs. Nuclear factor of activated T-cells c1 (NFATc1) mRNA expression tended to be decreased by daidzein, and was significantly decreased by genistein and DHA. Furthermore, the combination of daidzein and DHA caused significant reduction in NFATc1 mRNA expression compared to the control. In RAW 264.7 cells,
Interleukin-6 (IL-6) and interleukin-11 (IL-11) are known to influence osteoclast formation and bone resorption. In order to determine whether IL-6 and IL-11 could independently support human osteoclast formation, these factors were added to cultures of human peripheral blood mononuclear cells of the monocyte (CD14(+)) fraction in the presence of macrophage colony-stimulating factor (M-CSF). Under these conditions, IL-6 and IL-11 induced the formation of multinucleated cells which were positive for TRAP, VNR, and calcitonin receptor and capable of lacunar resorption. Osteoclastogenesis induced by IL-6 and IL-11 was inhibited by the addition of an anti-gp130 antibody but not by osteoprotegerin. These results indicate that IL-6 and IL-11, which are thought to play a role in several osteolytic bone disorders, are directly capable of inducing osteoclast formation by a RANKL-independent mechanism.
TY - JOUR. T1 - Eriodictyol Inhibits RANKL-Induced Osteoclast Formation and Function Via Inhibition of NFATc1 Activity. AU - Song, Fangming. AU - Zhou, Lin. AU - Zhao, J.. AU - Liu, Q.. AU - Yang, Mingli. AU - Tan, R.. AU - Xu, J.. AU - Zhang, G.. AU - Quinn, J.M.W.. AU - Tickner, Jennifer. AU - Huang, Y.. AU - Xu, Jiake. PY - 2016/9. Y1 - 2016/9. N2 - © 2016 Wiley Periodicals, Inc. Receptor activator of nuclear factor kappa-B ligand (RANKL) induces differentiation and function of osteoclasts through triggering multiple signaling cascades, including NF-?B, MAPK, and Ca2+-dependent signals, which induce and activate critical transcription factor NFATc1. Targeting these signaling cascades may serve as an effective therapy against osteoclast-related diseases. Here, by screening a panel of natural plant extracts with known anti-inflammatory, anti-tumor, or anti-oxidant properties for possible anti-osteoclastogenic activities we identified Eriodictyol. This flavanone potently suppressed ...
Osteoclasts demonstrate ontogenetic changes in site specificity. Figure 3 and Table 1 clearly show that TRAP-positive osteoclasts are absent during initial postnatal development. This does not preclude the presence of osteoclasts at this time. In fact, Rice et al. (1997) have shown MMP-9-positive osteoclasts at these ages. The probable reason for this is because the calvarial bone being deposited at these newborn stages is low in mineral content. The matrix metalloproteinase, MMP-9, is thought to be sufficient for the early requirements of bone resorption. Later in postnatal development as bone becomes more densely mineralized, TRAP-positive osteoclasts would be required for resorption. Congruent with this explanation, osteoclasts are observed along concave and straight sagittal suture margins at 10 days postnatal. By 21 days postnatal, one can observe osteoclasts along convex margins as well. The occurrence of osteoclasts along convex and concave regions increases incrementally until 42 days ...
IL-1 is a proinflammatory cytokine that acts as an important mediator of the peripheral immune response during infection and inflammation (33). It is also known that IL-1 can induce bone destruction in a variety of diseases such as osteoporosis, rheumatoid arthritis, and periodontal disease (34, 35). IL-1 stimulates osteoclast differentiation, fusion, and activation (35). In this paper, we examined the direct effect of IL-1 on osteoclast precursors which led to the elucidation of a previously unknown mechanism of downstream signaling pathways during IL-1-induced osteoclastogenesis.. Although TNF-α and IL-1 can activate early signaling pathways including NF-κB, JNK, and p38, which are important for RANKL-induced osteoclast differentiation, TNF-α alone has been shown to induce osteoclast differentiation in vitro (21, 36). IL-1 activates mature osteoclasts, thereby enhancing bone resorption (35), but our data along with previous studies (35, 36) demonstrate that IL-1 alone is insufficient to ...
DESCRIPTION (provided by applicant): Periodontitis is a chronic inflammatory disease that leads to osteoclast-mediated bone destruction, resulting in tooth loss. The cytokine TGF-beta initially promotes the inflammatory response, but ultimately slows bone loss by suppressing bone degradation. On the basis of published reports and our preliminary data, it appears likely that an important component of this repression is the initiation of osteoclast apoptosis. Reducing osteoclast numbers through targeting osteoclast survival pathways may provide important future therapeutic targets to slow pathological bone loss during periodontitis, osteoporosis, and tumor-driven osteolysis. It is the goal of this research to define the molecular pathways linking TGF- beta to regulation of osteoclast apoptosis. In preliminary studies, we observed that (i) osteoclast survival is due to continual activation of the MEK/ERK and AKT/NF(B survival pathways; (ii) PI3K coordinately activates these pathways to promote ...
The osteoclast is a bone-degrading polykaryon. Recent studies have clarified the differentiation of this cell and the biochemical mechanisms it uses to resorb bone. The osteoclast derives from a monocyte/macrophage precursor. Osteoclast formation requires permissive concentrations of M-CSF and is driven by contact with mesenchymal cells in bone that bear the TNF-family ligand RANKL. Osteoclast precursors express RANK, and the interaction between RANKL and RANK (which is inhibited by OPG) is the major determinant of osteoclast formation. Hormones, such as PTH/PTHrP, glucocorticoids and 1,25(OH)2D3, and humoral factors, including TNFalpha, interleukin-1, TGFss and prostaglandins, influence osteoclast formation by altering expression of these molecular factors. TNFalpha, IL-6 and IL-11 have also been shown to promote osteoclast formation by RANKL-independent processes. RANKL-dependent/independent osteoclast formation is likely to play an important role in conditions where there is pathological bone
Human osteoclast formation from monocyte precursors under the action of receptor activator of nuclear factor-{kappa}B ligand (RANKL) was suppressed by granulocyte macrophage colony-stimulating factor (GM-CSF), with down-regulation of critical osteoclast-related nuclear factors. GM-CSF in the presence of RANKL and macrophage colony-stimulating factor resulted in mononuclear cells that were negative for tartrate-resistant acid phosphatase (TRAP) and negative for bone resorption. CD1a, a dendritic cell marker, was expressed in GM-CSF, RANKL, and macrophage colony-stimulating factor-treated cells and absent in osteoclasts. Microarray showed that the CC chemokine, monocyte chemotactic protein 1 (MCP-1), was profoundly repressed by GM-CSF. Addition of MCP-1 reversed GM-CSF suppression of osteoclast formation, recovering the bone resorption phenotype. MCP-1 and chemokine RANTES (regulated on activation normal T cell expressed and secreted) permitted formation of TRAP-positive multinuclear cells in the ...
Multinucleated osteoclasts differentiate from hematopoietic progenitors of the monocyte/macrophage lineage. Because of its pivotal role in bone resorption, regulation of osteoclast differentiation is a potential therapeutic approach to the treatment of erosive bone disease. In this study, we have found that fucoidan, a sulfated polysaccharide extracted from brown seaweed, inhibited osteoclast differentiation. In particular, addition of fucoidan into the early stage osteoclast cultures significantly inhibited receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast formation, thus suggesting that fucoidan affects osteoclast progenitors. Furthermore, fucoidan significantly inhibited the activation of RANKL-dependent mitogen-activated protein kinases (MAPKs) such as JNK, ERK, and p38, and also c-Fos and NFATc1, which are crucial transcription factors for osteoclastogenesis. In addition, the activation of NF-κB, which is an upstream transcription factor modulating NFATc1
Wear particles derived from implant biomaterials induce a pronounced foreign body macrophage response in both the pseudocapsule and pseudomembrane surrounding arthroplasty components.28 29 The clinical severity and rapidly of onset of aseptic loosening can be correlated with both the amount of wear particle deposition and the extent of the macrophage response in these periprosthetic tissue.30-32 In this study we have shown that the capacity of arthroplasty macrophages to differentiate into osteoclasts is OPGL dependent and that this process is inhibited by OPG in a dose dependent fashion.. Our results show that the inflammatory foreign body macrophage infiltrate in periprosthetic tissues, surrounding loose arthroplasty components, contains mononuclear osteoclast precursors and that these cells express the phenotypic characteristics of macrophages and not osteoclasts. Post-mitotic osteoclast precursors of marrow origin have been shown to lose and to acquire macrophage and osteoclast markers ...
TY - JOUR. T1 - Isolation of a human homolog of osteoclast inhibitory lectin that inhibits the formation and function of osteoclasts. AU - Yun, Shan Hu. AU - Zhou, Hong. AU - Myers, Damian. AU - Quinn, Julian M W. AU - Atkins, Gerald J.. AU - Ly, Chi. AU - Gange, Christine. AU - Kartsogiannis, Vicky. AU - Elliott, Jan. AU - Kostakis, Panagiota. AU - Zannettino, Andrew C W. AU - Cromer, Brett. AU - Mckinstry, William J.. AU - Findlay, David M.. AU - Gillespie, Matthew T.. AU - Kong, Wah Ng. PY - 2004/1/1. Y1 - 2004/1/1. N2 - Osteoclast inhibitory lectin (OCIL) is a newly recognized inhibitor of osteoclast formation. We identified a human homolog of OCIL and its gene, determined its regulation in human osteoblast cell lines, and established that it can inhibit murine and human osteoclast formation and resorption. OCIL shows promise as a new antiresorptive. Introduction: Murine and rat osteoclast inhibitory lectins (mOCIL and rOCIL, respectively) are type II membrane C-type lectins expressed by ...
IL-12, like IL-18, was shown to potently inhibit osteoclast formation in cultures of cocultures of murine osteoblast and spleen cells, as well as in adult spleen cells treated with M-CSF and receptor activator of NF-kappaB ligand (RANKL). Neither IL-12 nor IL-18 was able to inhibit RANKL-induced osteoclast formation in cultured RAW264.7 cells, demonstrating that IL-12, like IL-18, was unable to act directly on osteoclastic precursors. IL-12, like IL-18, was found to act by T cells, since depletion of T cells from the adult spleen cell cultures ablated the inhibitory action of IL-12 and addition of either CD4 or CD8 T cells from C57BL/6 mice to RANKL-stimulated RAW264.7 cultures permitted IL-12 or IL-18 to be inhibitory. Additionally, IL-12 was still able to inhibit osteoclast formation in cocultures with osteoblasts and spleen cells from either GM-CSF R(-/-) mice or IFN-gamma R(-/-) mice, indicating that neither GM-CSF nor IFN-gamma was mediating osteoclast inhibition in these cultures. Combined, IL-18
We reported that interleukin (IL) 6 alone cannot induce osteoclast formation in cocultures of mouse bone marrow and osteoblastic cells, but soluble IL-6 receptor (IL-6R) strikingly triggered osteoclast formation induced by IL-6. In this study, we examined the mechanism of osteoclast formation by IL-6 and related cytokines through the interaction between osteoblastic cells and osteoclast progenitors. When dexamethasone was added to the cocultures, IL-6 could stimulate osteoclast formation without the help of soluble IL-6R. Osteoblastic cells expressed a very low level of IL-6R mRNA, whereas fresh mouse spleen and bone marrow cells, both of which are considered to be osteoclast progenitors, constitutively expressed relatively high levels of IL-6R mRNA. Treatment of osteoblastic cells with dexamethasone induced a marked increase in the expression of IL-6R mRNA. By immunoblotting with antiphosphotyrosine antibody, IL-6 did not tyrosine-phosphorylate a protein with a molecular mass of 130 kD in ...
Kahweol is a natural product in coffee beans. It exhibits a wide variety of biological activities, including inhibiting RANKL-induced osteoclast generation, inducing cell cycle arrest and apoptosis in oral squamous cell carcinoma cells, preventing aflatoxin B1 induced DNA adduct formation, and suppressing H2O2-induced DNA damage and oxidative stress.
Inoxitol hexakisphosphate (IP6) has been found to have an important role in biomineralization and a direct effect inhibiting mineralization of osteoblasts in vitro without impairing extracellular matrix production and expression of alkaline phosphatase. IP6 has been proposed to exhibit similar effects to those of bisphosphonates on bone resorption, however, its direct effect on osteoclasts (OCL) is presently unknown. The aim of the present study was to investigate the effect of IP6 on the RAW 264.7 monocyte/macrophage mouse cell line and on human primary osteoclasts. On one hand, we show that IP6 decreases the osteoclastogenesis in RAW 264.7 cells induced by RANKL, without affecting cell proliferation or cell viability. The number of TRAP positive cells and mRNA levels of osteoclast markers such as TRAP, calcitonin receptor, cathepsin K and MMP-9 was decreased by IP6 on RANKL-treated cells. On the contrary, when giving IP6 to mature osteoclasts after RANKL treatment, a significant increase of ...
Based on our earlier observation that caspase-3 is present in osteoclasts that are not undergoing apoptosis, we investigated the role of this protein in the differentiation of primary osteoclasts and RAW264.7 cells (Szymczyk KH, et al, 2005, Caspase-3 activity is necessary for RANKL-induced osteoclast differentiation. The Proceedings of the 8th ICCBMT). We noted that osteoclast numbers are decreased in long bones of procaspase-3 knockout mice and that receptor activator of NF-κB ligand (RANKL) does not promote differentiation of isolated preosteoclasts. In addition, after treatment with inhibitors of caspase-3 activity, neither the wild-type primary nor the RAW264.7 cells express TRAP or became multinucleated. We found that immediately following RANKL treatment, procaspase-3 is cleaved and the activated protein is localized to lipid regions of the plasma membrane and the cytosol. We developed RAW264.7 procaspase-3 knockdown clonal cell lines using RNAi technology. Again, treatment with RANKL fails to
TY - JOUR. T1 - NMDA glutamate receptors are expressed by osteoclast precursors and involved in the regulation of osteoclastogenesis. AU - Merle, Blandine. AU - Itzstein, Cecile. AU - Delmas, Pierre D. AU - Chenu, Chantal. N1 - Copyright 2003 Wiley-Liss, Inc.. PY - 2003/10/1. Y1 - 2003/10/1. N2 - We previously identified functional N-methyl-D-aspartate (NMDA) glutamate receptors in mature osteoclasts and demonstrated that they are involved in bone resorption in vitro. In the present work, we studied the expression of NMDA receptors (NMDAR) by osteoclast precursors and their role in osteoclastogenesis using two in vitro models, the murine myelomonocytic RAW 264.7 cell line and mouse bone marrow cells, both of which differentiate into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF) and Rank ligand (RankL). Using RT-PCR analysis with specific probes, we showed that RAW 264.7 cells and mouse bone marrow cells express mRNA of NMDAR subunits NMDA receptor 1 (NR1) and NMDA ...
To determine whether synovial fluid (SF) macrophages isolated from the SF of osteoarthritis (OA), rheumatoid arthritis (RA) and pyrophosphate arthropathy (PPA) joints are capable of osteoclast formation, and to investigate the cellular and humoral factors required for this to occur, SF macrophages (CD14+) were isolated from the knee joint SF from patients with OA, RA and PPA and cultured for up to 14 days with macrophage-colony stimulating factor (M-CSF) and soluble receptor activator for nuclear factor-kappaB ligand (RANKL) or tumour-necrosis factor-alpha (TNFalpha) and interleukin-1alpha (IL-1alpha). Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR), F-actin ring formation and lacunar resorption. Osteoclast formation and lacunar resorption was seen in RANKL-treated cultures of SF macrophages isolated from OA, RA and PPA joints with the largest amount of resorption noted in RA and PPA SF macrophage cultures. In TNFalpha/IL
Y1 receptor (Y1R)-signalling pathway plays a pivotal role in the regulation of bone metabolism. The lack of Y1R-signalling stimulates bone mass accretion that has been mainly attributed to Y1R disruption from bone-forming cells. Still, the involvement of Y1R-signalling in the control of bone-resorbing cells remained to be explored. Therefore, in this study we assessed the role of Y1R deficiency in osteoclast formation and resorption activity. Here we demonstrate that Y1R germline deletion (Y1R(-/-)) led to increased formation of highly multinucleated (n | 8) osteoclasts and enhanced surface area, possibly due to monocyte chemoattractant protein-1 (MCP-1) overexpression regulated by RANKL-signalling. Interestingly, functional studies revealed that these giant Y1R(-/-) multinucleated cells produce poorly demineralized eroded pits, which were associated to reduce expression of osteoclast matrix degradation markers, such as tartrate-resistant acid phosphatase-5b (TRAcP5b), matrix metalloproteinase-9 (MMP-9)
An osteoclast (from the Greek words for bone (ὀστέον), and broken (κλαστός)) is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodelling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption. This process also helps regulate the level of blood calcium. An odontoclast (/odon·to·clast/; o-don´to-klast) is an osteoclast associated with absorption of the roots of deciduous teeth. An osteoclast is a large multinucleated cell and human osteoclasts on bone typically have five nuclei and are about 150-200 µm in diameter. When osteoclast-inducing cytokines are used to convert macrophages to osteoclasts, very large cells that may reach 100 µm in diameter occur. These may have dozens of nuclei, and typically express major osteoclast proteins but have significant ...
BACKGROUND: Interleukin-32 (IL-32) is a newly described cytokine produced after stimulation by IL-2 or IL-18 and IFN-gamma. IL-32 has the typical properties of a pro-inflammatory mediator and although its role in rheumatoid arthritis has been recently reported its effect on the osteoclastogenesis process remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we have shown that IL-32 was a potent modulator of osteoclastogenesis in vitro, whereby it promoted the differentiation of osteoclast precursors into TRAcP+ VNR+ multinucleated cells expressing specific osteoclast markers (up-regulation of NFATc1, OSCAR, Cathepsin K), but it was incapable of inducing the maturation of these multinucleated cells into bone-resorbing cells. The lack of bone resorption in IL-32-treated cultures could in part be explain by the lack of F-actin ring formation by the multinucleated cells generated. Moreover, when IL-32 was added to PBMC cultures maintained with soluble RANKL, although the number of newly
Since their discovery in 1873 there has been considerable debate about their origin. Three theories were dominant: from 1949 to 1970 the connective tissue origin was popular, which stated that osteoclasts and osteoblasts are of the same lineage, and osteoblasts fuse together to form osteoclasts. After years of controversy it is now clear that these cells develop from the self fusion of macrophages.[9] It was in the beginning of 1980 that the monocyte phagocytic system was recognized as precursor of osteoclasts.[10] Osteoclast formation requires the presence of RANKL (receptor activator of nuclear factor κβ ligand) and M-CSF (Macrophage colony-stimulating factor). These membrane-bound proteins are produced by neighbouring stromal cells and osteoblasts, thus requiring direct contact between these cells and osteoclast precursors. M-CSF acts through its receptor on the osteoclast, c-fms (colony-stimulating factor 1 receptor), a transmembrane tyrosine kinase-receptor, leading to secondary messenger ...
Since their discovery in 1873 there has been considerable debate about their origin. Three theories were dominant: from 1949 to 1970 the connective tissue origin was popular, which stated that osteoclasts and osteoblasts are of the same lineage, and osteoblasts fuse together to form osteoclasts. After years of controversy it is now clear that these cells develop from the self fusion of macrophages.[9] It was in the beginning of 1980 that the monocyte phagocytic system was recognized as precursor of osteoclasts.[10] Osteoclast formation requires the presence of RANKL (receptor activator of nuclear factor κβ ligand) and M-CSF (Macrophage colony-stimulating factor). These membrane-bound proteins are produced by neighbouring stromal cells and osteoblasts, thus requiring direct contact between these cells and osteoclast precursors. M-CSF acts through its receptor on the osteoclast, c-fms (colony-stimulating factor 1 receptor), a transmembrane tyrosine kinase-receptor, leading to secondary messenger ...
Bone resorption relies on the extracellular acidification function of V-ATPase (vacuolar-type proton-translocating ATPase) proton pump(s) present in the plasma membrane of osteoclasts. The exact configuration of the osteoclast-specific ruffled border V-ATPases remains largely unknown. In the present study, we found that the V-ATPase subunit Atp6v1c1 (C1) is highly expressed in osteoclasts, whereas subunits Atp6v1c2a (C2a) and Atp6v1c2b (C2b) are not. The expression level of C1 is highly induced by RANKL [receptor activator for NF-κB (nuclear factor κB) ligand] during osteoclast differentiation; C1 interacts with Atp6v0a3 (a3) and is mainly localized on the ruffled border of activated osteoclasts. The results of the present study show for the first time that C1-silencing by lentivirus-mediated RNA interference severely impaired osteoclast acidification activity and bone resorption, whereas cell differentiation did not appear to be affected, which is similar to a3 silencing. The F-actin ...
Osteoclasts are large, multinucleated cells whose primary function is bone resorption. This process is regulated at multiple levels, including the proliferation and homing of osteoclast progenitors and their fusion into multinucleated cells (reviewed by Teitelbaum, 2000). Upon identification of appropriate resorption sites, osteoclasts reorganize their small matrix adhesions - podosomes - into a circular adhesion structure at the cell periphery known as the `sealing zone, and secrete protons and lysosomal enzymes into the space between the cell and the bone surface (Nesbitt and Horton, 1997; Salo et al., 1997). These structures form readily on bone surfaces; similar organization of podosome super-structures was observed in cells grown on standard tissue culture surfaces (Calle et al., 2004; Lakkakorpi et al., 1993; Zambonin-Zallone et al., 1988).. Podosomes are small (∼1 μm in diameter) dot-like adhesion structures found in osteoclasts, macrophages, dendritic cells and several types of ...
Excessive osteoclast formation and bone resorption are key causes of osteoporosis. Natural compounds can serve as alternative therapeutic agents for the prevention and treatment of osteoporosis, and some natural compounds may have advantages over traditional drugs. Here, we report that the natural compound gambogic acid (GBA), which is bioavailable, effective, and less toxic, inhibits osteoclast formation, thereby attenuating osteoclastic bone resorption in vitro . Further in vivo studies demonstrated that GBA prevented ovariectomy(OVX)-induced bone loss in a dose-dependent manner. Moreover, we demonstrated that GBA suppressed RANKL-induced JNK, p38 and AKT phosphorylation. Taken together, our results demonstrate that GBA inhibits osteoclast formation in vitro and in vivo , suggesting that it is of potential value in the treatment of osteoclast-related diseases. ...
|i|Objective|/i|. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients.|i| Methods.|/i| Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers, in vitro OC differentiation assays, and qRT-PCR for OC specific genes was performed.|i| Results|/i|. After TNFi therapy, patients had reduced RANKL surface expression in B-lymphocytes and the frequency of circulating classical |svg xmlns:xlink=http://www.w3.org/1999/xlink xmlns=http://www.w3.org/2000/svg style=
TY - JOUR. T1 - Osteoclasts, mononuclear phagocytes, and c-Fos. T2 - New insight into osteoimmunology. AU - Matsuo, Koichi. AU - Ray, Neelanjan. PY - 2004/6/1. Y1 - 2004/6/1. N2 - Osteoimmunology is the emerging concept that certain molecules link the skeletal and immune systems. The transcription factor c-Fos, a component of activator protein-1 (AP-1), is essential for osteoclast differentiation. Mice lacking c-Fos are osteopetrotic owing to impaired osteoclast development. Recent studies suggest that in contrast to this positive role in osteoclastogenesis, c-Fos expression inhibits differentiation and activation of mononuclear phagocytes. Here, we focus on the contrasting roles of c-Fos in the bone and immune lineages. Both osteoclasts and mononuclear phagocytes are derived from common myeloid precursors. Osteoclasts resorb bone, whereas macrophages and myeloid dendritic cells phagocytose microbial pathogens, initiating innate and adaptive immunity. Differentiation of the common precursors ...
beta(3) integrin-null osteoclasts are dysfunctional, but their numbers are increased in vivo. In vitro, however, the number of beta(3)(-/-) osteoclasts is reduced because of arrested differentiation. This paradox suggests cytokine regulation of beta(3)(-/-) osteoclastogenesis differs in vitro and in vivo. In vitro, additional MCSF, but not receptor activator of NF-kappaB ligand (RANKL), completely rescues beta(3)(-/-) osteoclastogenesis. Similarly, activation of extracellular signal-regulated kinases (ERKs) and expression of c-Fos, both essential for osteoclastogenesis, are attenuated in beta(3)(-/-) preosteoclasts, but completely restored by additional MCSF. In fact, circulating and bone marrow cell membrane-bound MCSFs are enhanced in beta(3)(-/-) mice, correlating with the increase in the osteoclast number. To identify components of the MCSF receptor that is critical for osteoclastogenesis in beta(3)(-/-) cells, we retrovirally transduced authentic osteoclast precursors with chimeric c-Fms constructs
TY - JOUR. T1 - Cytokine regulation and the signaling mechanism of osteoclast inhibitory peptide-1 (OIP-1/hSca) to inhibit osteoclast formation. AU - Koide, Masanori. AU - Maeda, Hidefumi. AU - Roccisana, Jennifer L.. AU - Kawanabe, Noriaki. AU - Reddy, Sakamuri V.. PY - 2003/3/1. Y1 - 2003/3/1. N2 - The osteoclast (OCL) is the primary bone resorbing cell. OCL formation and activity is regulated by local factors produced in the bone microenvironment. We recently identified OCL inhibitory peptide-1 (OIP-1/ hSca) as a novel inhibitor of OCL formation and bone resorption that is produced by OCLs. OIP-1 is a glycosylphosphatidyl-inositol (GPI)-linked membrane protein (16 kDa) related to the mouse Ly-6 family of hematopoietic proteins. OIP-1 mRNA is expressed in human OCL precursors, granulocyte-macrophage colony-forming unit (GM-CFU), bone marrow cells, and osteoblast cells. We used cycle-dependent reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, which further demonstrated that ...
To better understand the roles of TGF-beta in bone metabolism, we investigated osteoclast survival in response TGF-beta and found that TGF-beta inhibited apoptosis. We examined the receptors involved in promotion of osteoclast survival and found that the canonical TGF-beta receptor complex is involved in the survival response. The upstream MEK kinase TAK1 was rapidly activated following TGF-beta treatment. Since osteoclast survival involves MEK, AKT, and NFkappaB activation, we examined TGF-beta effects on activation of these pathways and observed rapid phosphorylation of MEK, AKT, IKK, IkappaB, and NFkappaB. The timing of activation coincided with SMAD activation and dominant negative SMAD expression did not inhibit NFkappaB activation, indicating that kinase pathway activation is independent of SMAD signaling. Inhibition of TAK1, MEK, AKT, NIK, IKK, or NFkappaB repressed TGF-beta-mediated osteoclast survival. Adenoviral-mediated TAK1 or MEK inhibition eliminated TGF-beta-mediated kinase pathway
TY - JOUR. T1 - TGF-β coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survival. AU - Gingery, Anne. AU - Bradley, Elizabeth W.. AU - Pederson, Larry. AU - Ruan, Ming. AU - Horwood, Nikki J.. AU - Oursler, Merry Jo. PY - 2008/9/10. Y1 - 2008/9/10. N2 - To better understand the roles of TGF-β in bone metabolism, we investigated osteoclast survival in response TGF-β and found that TGF-β inhibited apoptosis. We examined the receptors involved in promotion of osteoclast survival and found that the canonical TGF-β receptor complex is involved in the survival response. The upstream MEK kinase TAK1 was rapidly activated following TGF-β treatment. Since osteoclast survival involves MEK, AKT, and NFκB activation, we examined TGF-β effects on activation of these pathways and observed rapid phosphorylation of MEK, AKT, IKK, IκB, and NFκB. The timing of activation coincided with SMAD activation and dominant negative SMAD expression did not inhibit NFκB activation, ...
Methods For in vitro validation of osteoclastogenesis mouse bone marrow derived cells were differentiated into tartrate-resistant acid phosphatase positive (TRAP+) mononuclear osteoclasts (pre-osteoclasts) and TRAP+ multinucleated mature osteoclasts in the presence of macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor kappaB ligand (RANKL). Cilengitide, kindly provided by Merck KGaA, was added in increasing concentrations (2nM to 20μM) to the culture. Moreover, we performed osteoclastogenesis assays on osteopontin, fibronectin and fibrinogen matrix coated plates. In order to asses for αvβ3 integrin independent adhesion, osteolastogenesis assays were performed on Poly-D-lysine coated plates. CIA was induced in male DBA/1 mice by immunisation with bovine type II collagen (CII) at day 1, followed by boosting at day 21. For the CIA prevention study mice were injected 15mg/kg cilengitide subcutaneously, 5 days per week, starting 1 day prior to CIA induction until ...
TY - JOUR. T1 - Immunological reaction in TNF-α-mediated osteoclast formation and bone resorption in vitro and in vivo. AU - Kitaura, Hideki. AU - Kimura, Keisuke. AU - Ishida, Masahiko. AU - Kohara, Haruka. AU - Yoshimatsu, Masako. AU - Takano-Yamamoto, Teruko. PY - 2013. Y1 - 2013. N2 - Tumor necrosis factor-α (TNF-α) is a cytokine produced by monocytes, macrophages, and T cells and is induced by pathogens, endotoxins, or related substances. TNF-α may play a key role in bone metabolism and is important in inflammatory bone diseases such as rheumatoid arthritis. Cells directly involved in osteoclastogenesis include macrophages, which are osteoclast precursor cells, osteoblasts, or stromal cells. These cells express receptor activator of NF-B ligand (RANKL) to induce osteoclastogenesis, and T cells, which secrete RANKL, promote osteoclastogenesis during inflammation. Elucidating the detailed effects of TNF-α on bone metabolism may enable the identification of therapeutic targets that can ...
2924 Genrally, prostatic cancer shows osteoblastic metastases, whereas the lesion also causes osteolysis. The present study was undertaken to test the effects of prostate cancer cell lines (LNCaP, DU145, PC3, and MDA PCa 2b) on osteoclastogenesis. Using a reverse transcription-polymerase chain reaction approach, we investigated the effects of crude conditioned medium (CM) obtained from prostate cancer cell lines on mRNA level of receptor activator of NF-κB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG) in mouse osteoblastic cell line, MC3T3-E1. Then we cocultured MC3T3-E1 with prostate cancer cell lines and evaluated mRNA level of RANKL and OPG in MC3T3-E1. Next, to investigate the effects on osteoclast precursor generated from mouse bone marrow treated with RANKL and MCSF, we cultured osteoclast precursor with crude CM obtained from prostate cancer cell lines in the presence or absence of RANKL or OPG. The number of multinucleated osteoclasts was evaluated by TRAP staining. Crude ...
Estrogen prevents osteoporotic bone loss by attenuating bone resorption; however, the molecular basis for this is unknown. Here, we report a critical role for the osteoclastic estrogen receptor alpha (ERalpha) in mediating estrogen-dependent bone maintenance in female mice. We selectively ablated ERalpha in differentiated osteoclasts (ERalpha(DeltaOc/DeltaOc)) and found that ERalpha(DeltaOc/DeltaOc) females, but not males, exhibited trabecular bone loss, similar to the osteoporotic bone phenotype in postmenopausal women. Further, we show that estrogen induced apoptosis and upregulation of Fas ligand (FasL) expression in osteoclasts of the trabecular bones of WT but not ERalpha(DeltaOc/DeltaOc) mice. The expression of ERalpha was also required for the induction of apoptosis by tamoxifen and estrogen in cultured osteoclasts. Our results support a model in which estrogen regulates the life span of mature osteoclasts via the induction of the Fas/FasL system, thereby providing an explanation for the
TY - JOUR. T1 - EGF-like ligands stimulate osteoclastogenesis by regulating expression of osteoclast regulatory factors by osteoblasts. T2 - Implications for osteolytic bone metastases. AU - Zhu, Ji. AU - Jia, Xun. AU - Xiao, Guozhi. AU - Kang, Yibin. AU - Partridge, Nicola C.. AU - Qin, Ling. PY - 2007/9/14. Y1 - 2007/9/14. N2 - Epidermal growth factor (EGF)-like ligands and their receptors constitute one of the most important signaling networks functioning in normal tissue development and cancer biology. Recent in vivo mouse models suggest this signaling network plays an essential role in bone metabolism. Using a coculture system containing bone marrow macrophage and osteoblastic cells, here we report that EGF-like ligands stimulate osteoclastogenesis by acting on osteoblastic cells. This stimulation is not a direct effect because osteoclasts do not express functional EGF receptors (EGFRs). Further studies reveal that EGF-like ligands strongly regulate the expression of two secreted osteoclast ...
Osteoclasts Culture Kit from B-Bridge International,Osteoclast cells form from a hematopoietic stem cells called monocytes. Osteoclasts resorb bone by attaching to the bone surface and lowering the surrounding pH to an acidic level of around 4.5. The bone mineral is then solubilized and the collagen degraded. Osteoclast differentiation and function,biological,biology supply,biology supplies,biology product
Hyaluronic acid (hyaluronan, HA) is a component of the extracellular matrix and is also used clinically to treat joint and cartilage diseases such as osteoarthritis. Chang et al. show that high molecular mass HA (HMM-HA), but not low molecular mass HA, inhibited osteoclast differentiation of bone marrow-derived macrophages in response to macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). HMM-HA did not block RANKL-stimulated osteoclastogenesis of RAW264.7 cells, which is independent of M-CSF. Although CD44 is one known receptor for HA, antibodies that block CD44 had no effect on the inhibition of osteoclast formation by HA. However, function-blocking antibodies against Toll-like receptor 4 (TLR4) blocked the inhibitory effect of HA, suggesting that HA was acting through the TLR4. TLR4-transfected cells bound labeled HA based on fluorescence-activated cell sorting analysis, and osteoclastogenesis of cells from mice with a nonfunctional TLR4 ...
Objective: To investigate the relationship between intestinal inflammation and the central and peripheral innate immune system, in the pathogenesis of HLA-B27 associated spondyloarthritis. Methods: The myeloid compartment of the bone marrow and blood of HLA-B27 transgenic (B27), control HLA-B7 transgenic (B7), and non-transgenic rats were evaluated by flow cytometry. Plasma from rats were assessed by ELISA for CCL2 and IL-1α levels. Rats were treated for 4 weeks with antibiotics and the blood and bone marrow myeloid compartments were evaluated by flow cytometry. The osteoclastogenic potential of bone marrow cells from antibiotic treated rats, in the presence or absence of TNFα, was evaluated in vitro. Results: B27 rats have substantially higher numbers of circulating Lin-CD172a+CD43l° monocytes than control animals, which significantly correlates with higher levels of plasma CCL2. Antibiotic treatment of B27 rats markedly reduced ileitis, plasma CCL2 and IL-1α levels, and the number of bone ...
Summary: Rapid progress has been made in recent years in our understanding of the mechanisms regulating the formation, activation, and survival of osteoclasts, which are derived from precursor cells in the myeloid lineage. In contrast, study of the regulation of osteoclast precursors (OCPs) has been relatively slow, in part because it has been hard to accurately identify them. However, following the discovery of cell-surface markers that facilitated purification of OCPs, recent studies have demonstrated that peripheral blood OCP numbers are increased in tumor necrosis factor (TNF)-mediated arthritis, both in animals and humans, and these numbers correlate with serum TNF levels. The increase can be reversed by anti-TNF therapy. Furthermore, the precursor cells that give rise to osteoclasts can also differentiate into other cell types, including dendritic cells. Receptor activator nuclear factor-κB ligand (RANKL) stimulates OCPs to produce pro-inflammatory cytokines and chemokines, and RANKL ...
Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene. IMO iPSCs were generated from a patient carrying a homozygous c.11279G|A (IVS18+1) mutation in TCIRG1 and transduced with a lentiviral vector expressing human TCIRG1. Embryoid bodies were generated and differentiated into monocytes. Non-adherent cells were harvested and further differentiated into osteoclasts on bovine bone slices. Release of the bone resorption biomarker CTX-I into the media of gene-corrected osteoclasts was 5-fold higher than that of the uncorrected osteoclasts and 35% of that of control osteoclasts. Bone resorption potential was confirmed by the presence of pits on the bones cultured with gene-corrected osteoclasts, absent in the uncorrected IMO osteoclasts. The disease phenotype was partially corrected in vitro, providing a valuable resource for therapy development for
Patients with defective osteoclastic acidification have increased numbers of osteoclasts, with decreased resorption, but bone formation that remains unchanged. We demonstrate that osteoclast survival is increased when acidification is impaired, and that impairment of acidification results in inhibition of bone resorption without inhibition of bone formation. We investigated the role of acidification in human osteoclastic resorption and life span in vitro using inhibitors of chloride channels (NS5818/NS3696), the proton pump (bafilomycin) and cathepsin K. We found that bafilomycin and NS5818 dose dependently inhibited acidification of the osteoclastic resorption compartment and bone resorption. Inhibition of bone resorption by inhibition of acidification, but not cathepsin K inhibition, augmented osteoclast survival, which resulted in a 150 to 300% increase in osteoclasts compared to controls. We investigated the effect of inhibition of osteoclastic acidification in vivo by using the rat ...
Bone disease is the most frequent complication in multiple myeloma (MM) resulting in osteolytic lesions, bone pain, hypercalcemia and renal failure. In MM bone disease the perfect balance between bone-resorbing osteoclasts (OCs) and bone-forming osteoblasts (OBs) activity is lost in favour of OCs, thus resulting in skeletal disorders. Since exosomes have been described for their functional role in cancer progression, we here investigate whether MM cell-derived exosomes may be involved in OCs differentiation. We show that MM cells produce exosomes which are actively internalized by Raw264.7 cell line, a cellular model of osteoclast formation. MM cell-derived exosomes positively modulate pre-osteoclast migration, through the increasing of CXCR4 expression and trigger a survival pathway. MM cell-derived exosomes play a significant pro-differentiative role in murine Raw264.7 cells and human primary osteoclasts, inducing the expression of osteoclast markers such as Cathepsin K (CTSK), Matrix ...
Osteoclasts are a bone cell type responsible for the breakdown of bone. They display cell surface integrins that help activate signaling cascades that control the differentiation and function of osteoclasts. The kindlins are a family of proteins that are involved in activating integrin function and enhancing cell attachment to substrates. Kindlin3 is expressed solely in hematopoietic cells, including osteoclasts and their precursors. Mutations in kindlin3 are associated with a human syndrome, Leukocyte Adhesion Deficiency III (LAD-III) whose symptoms include osteopetrosis, which is bone brittleness due to non-functioning osteoclasts. The kindlin3 C-terminal tail is composed of three FERM (integrin-binding) domains, F1, F2, and F3 and one PH (membrane lipid-binding) domain that interrupts the F2 domain. The goal of this work is to determine the roles of kindlin3 and its domains in affecting osteoclast differentiation and function. Our studies demonstrated that kindlin3 is upregulated during ...
TY - JOUR. T1 - Novel inhibitors of RANKL-induced osteoclastogenesis. T2 - Design, synthesis, and biological evaluation of 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-diones. AU - Lee, Chia Chung. AU - Liu, Fei Lan. AU - Chen, Chun Liang. AU - Chen, Tsung Chih. AU - Liu, Feng Cheng. AU - Ahmed Ali, Ahmed Atef. AU - Chang, Deh Ming. AU - Huang, Hsu Shan. PY - 2015/7/23. Y1 - 2015/7/23. N2 - A series of novel 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione derivatives were synthesized and evaluated for their inhibitory effects on osteoclast activities by using TRAP-staining assay. Among the tested compounds, 3d and 3h exhibited more potent osteoclast-inhibitory activities than the lead compound NDMC503 (a ring-fused structure of NDMC101), as reported in our previous study. Both 3d and 3h exhibited two-fold increase in activity compared to NDMC503. In addition, our biological results indicated that 3d and 3h could suppress RANKL-induced ...
Background/Purpose: Ebselen is a non-toxic seleno-organic drug with anti-inflammatory and antioxidant properties that is currently being examined in clinical trials to prevent and treat various diseases, including atherosclerosis, stroke, and cancer/We investigated the effects of ebselen on RANKL-induced differentiation of osteoclasts and their functions and the underlying molecular mechanisms. Furthermore, we determined the effects of ebselen on LPS-induced bone erosion in vivo. Methods: We cultured BMMs for 4 days in the condition of M-CSF and RANKL pretreated with ebselen. The cells were then stained with TRAP solution, rhodamine-conjugated phalloidin for F-actin ring labeling and DAPI solution to detect apoptotic body formation. The change of F-actin ring on mature osteoclasts induced by ebselen was quantified by calculating the ratio of actin ring positive (AR+) osteoclasts versus actin ring negative (AR-) osteoclasts. to detect the formation of apoptotic osteoclasts, we performed TUNEL ...
Do you have a protocol for osteoclast resorption on dentine slices? I have done a literature search (1966-present) and the seminal article seems to be Boyde & Jones (1984) Resorption of dentine by isolated osteoclasts in vitro. Br Dent J 156:216-220. Help! Our provencial library doesnt have this journal. Donna Montague, M.S. Research Associate Physiology/Biophysics and Orthopaedic Surgery University of Arkansas for Medical Sciences (501) 603-1239 ...
Author: Rumpler, M. et al.; Genre: Meeting Abstract; Published in Print: 2011-05-07; Title: Microcracks and osteoclast resorption activity in vitro
TY - JOUR. T1 - Calcitonin receptor antibodies in the identification of osteoclasts. AU - Quinn, J. M W. AU - Morfis, M.. AU - Lam, M. H C. AU - Elliott, J.. AU - Kartsogiannis, V.. AU - Williams, Elizabeth D.. AU - Gillespie, M. T.. AU - Martin, T. J.. AU - Sexton, P. M.. PY - 1999/1/1. Y1 - 1999/1/1. N2 - Osteoclasts are the cells responsible for bone resorption, and their number and rate of formation are critical in determining bone mass. To identify and quantify osteoclasts, as well as to study their formation in bone and in osteoclastogenic cultures, osteoclast-specific cell markers are required. Only the calcitonin receptor (CTR) expression unambiguously identifies osteoclasts and distinguishes them from macrophage polykaryons. However, present autoradiographic methods for CTR detection are cumbersome and time consuming. We have developed rabbit polyclonal antibodies specific for the C-terminal intracellular domain of the mouse and rat C1a CTR. These antibodies labeled HEK-293 cells stably ...
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TY - JOUR. T1 - Supplementation with a low-moderate dose of n-3 long-chain PUFA has no short-term effect on bone resorption in human adults. AU - Appleton, K M. AU - Fraser, W D. AU - Rogers, P J. AU - Ness, A R. AU - Tobias, J H. PY - 2011/4. Y1 - 2011/4. N2 - Abstract Previous research suggests that n-3 PUFA may play a role in bone health. The present analysis aimed to investigate the impact of n-3 PUFA supplementation on bone resorption in adult men and women. Serum samples from 113 mild-moderately depressed individuals (twenty-six males and eighty-seven females, aged 18-67 years) randomised to receive 1·48 g EPA+DHA/d (n 53) or placebo (n 60) for 12 weeks as part of a large recent randomised controlled trial were assayed for n-3 PUFA status and a bone resorption marker, C-terminal cross-linking telopeptide of type 1 collagen (β-CTX). Regression analyses revealed that n-3 PUFA status following supplementation was associated with randomisation (placebo/n-3 PUFA) (B = 3·25, 95 % CI 2·60, ...
Bone erosion is a hallmark of rheumatoid arthritis. Recent evidence from experimental arthritis suggests that osteoclasts are essential for the formation of local bone erosions. Two essential regulators of osteoclastogenesis have recently been described: the receptor-activator of nuclear factor kappa B ligand, which promotes osteoclast maturation, and osteoprotegerin (OPG), which blocks osteoclastogenesis. The present review summarizes the current knowledge on the role of osteoclasts in local bone erosion. In addition, the role of OPG as a therapeutic tool to inhibit local bone erosion is addressed. Finally, evidence for OPG as an inhibitor of systemic inflammatory bone loss is discussed.
The Arg-Gly-Asp (RGD)-binding integrin αVβ3is highly expressed on osteoclasts and has been proposed to mediate cell-matrix adhesion required for osteoclast-mediated bone resorption. Antagonism of this receptor should prevent stable osteoclast adhesion and thereby inhibit bone resorption. We have generated an orally bioavailable, nonpeptide RGD mimetic αvβ3antagonist, SB 265123, which prevents bone loss in vivo when dosed by oral administration. SB 265123 binds αvβ3and the closely related integrin αvβ5 with high affinity (Ki = 3.5 and 1.3 nM, respectively), but binds only weakly to the related RGD-binding integrins αIIbβ3(Ki ,1 μM) and α5β1 (Ki ,1 μM). The compound inhibits αvβ3-mediated cell adhesion with an IC50 = 60 nM and more importantly, inhibits human osteoclast-mediated bone resorption in vitro with an IC50 = 48 nM. In vivo, SB 265123 completely blocks bone resorption in a thyroparathyroidectomized rat model of acute bone resorption when dosed at 2.5 mg/kg/h by continuous ...
Identification of Nedd9 as a TGF-β-Smad2-3 Target Gene Involved in RANKL-Induced Osteoclastogenesis by Comprehensive Analysis. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Osteoclasts are specialized polyploid cells that resorb bone tissue. polyploidy (they contained nuclei with more than the diploid match of chromosomes (>2N)) test with Welchs correction and are offered as means ± S.D. TAME A value < 0.05 was considered significant. Results RANKL Stimulation Increases Basal Proliferation of BMMs To determine the impact of RANKL activation around the cell cycle during osteoclast development we first examined the proportions of cells in the G1 TAME and S/G2/M phases during RANKL-induced osteoclast differentiation. Fucci double-transgenic mouse-derived bone marrow monocytes Rabbit Polyclonal to CDK1/CDC2 (phospho-Thr14). (dTg-BMMs) had been activated with or without RANKL in the current presence of M-CSF as well as the proportions from the cells positive for green fluorescence (S/G2/M stage) and crimson fluorescence (G1 stage) had been measured by stream cytometry. The percentage of TAME green cells elevated 24 h after RANKL arousal but this enhance vanished 48 h ...
Psoriatic arthritis (PsA) is an inflammatory joint disease characterized by extensive bone resorption. The mechanisms underlying this matrix loss have not been elucidated. We report here that blood samples from PsA patients, particularly those with bone erosions visible on plain radiographs, exhibit a marked increase in osteoclast precursors (OCPs) compared with those from healthy controls. Moreover, PsA PBMCs readily formed osteoclasts in vitro without exogenous receptor activator of NF-κB ligand (RANKL) or MCSF. Both osteoprotegerin (OPG) and anti-TNF antibodies inhibited osteoclast formation. Additionally, cultured PsA PBMCs spontaneously secreted higher levels of TNF-α than did healthy controls. In vivo, OCP frequency declined substantially in PsA patients following treatment with anti-TNF agents. Immunohistochemical analysis of subchondral bone and synovium revealed RANK-positive perivascular mononuclear cells and osteoclasts in PsA specimens. RANKL expression was dramatically upregulated ...
The osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. Osteoclastogenesis is mainly regulated by signaling pathways activated by RANK and immune receptors, whose ligands are expressed on the surface of osteoblasts. Signaling from RANK changes gene expression patterns through transcription factors like NFATc1 and characterizes the active osteoclast ...
Osteoporosis is a skeletal disease leading to an increased risk of bone fracture. Using a mouse osteoporosis model induced by administration of a receptor activator of nuclear factor kappa-B ligand (RANKL), salubrinal was recently reported as a potential therapeutic agent. To evaluate the role of salubrinal in cellular fates as well as migratory and adhesive functions of osteoclast/osteoblast precursors, we examined the development of primary bone marrow-derived cells in the presence and absence of salubrinal. We addressed a question: are salubrinals actions more potent to the cells isolated from the osteoporotic mice than those isolated from the control mice? Using the RANKL-injected and control mice, bone marrow-derived cells were harvested. Osteoclastogenesis was induced by macrophage-colony stimulating factor and RANKL, while osteoblastogenesis was driven by dexamethasone, ascorbic acid, and β-glycerophosphate. The results revealed that salubrinal suppressed the numbers of colony forming-unit (CFU
The microphthalmia transcription factor (MITF), a basic-helix-loop-helix zipper factor, regulates distinct target genes in several cell types. We hypothesized that interaction with the Ets family factor PU.1, whose expression is limited to hematopoietic cells, might be nec- essary for activation of target genes like tartrate-resistant acid phosphatase (TRAP) in osteoclasts. Several lines of evidence were consistent with this model. The combination of MITF and PU.1 synergistically activated the TRAP promoter in transient assays. This activation was dependent on intact binding sites for both factors in the TRAP promoter. MITF and PU.1 physically interacted when coexpressed in COS cells or in vitro when purified recombinant proteins were studied. The minimal regions of MITF and PU.1 required for the interaction were the basic-helix-loop-helix zipper domain and the Ets DNA binding domain, respectively. Significantly, mice heterozygous for both the mutant mi allele and a PU.1 null allele developed ...
Injection of RANKL CDK inhibition into RANKL deficient mice induced many osteoclasts in bone although not delicate tissues. These effects advise that osteoblasts establish the put of osteoclastogenesis from haemopoietic stem cells in bone. We subsequent explored roles of osteoclasts in ectopic bone formation induced by BMP utilizing op/op and c fos deficient osteopetrotic mice. The ectopic bones formed in op/op mice showed particularly tough surfaces, whereas those in wild form mice showed smooth ones. Bone mineral density of BMP induced ectopic bone in op/op mice was about 2 times increased than that in wild kind mice. TRAP constructive osteoclasts exhibit in outer of the ectopic bone while in the wild form mice. In op/op mice, despite the fact that osteoclasts strongly exhibit in inside with the BMP induced ectopic bone, TRAP positive osteoclasts didnt exhibit in outer of the BMP induced ectopic bone.. Furthermore, order BYL719 the accentuation of the BMP induced ectopic bone formation did ...
There are many causes of inflammatory osteolysis, but regardless of etiology and cellular contexts, the osteoclast is the bone-degrading cell. Thus, the impact of inflammatory cytokines on osteoclast formation and function was among the most important discoveries advancing the treatment of focal osteolysis, leading to development of therapeutic agents that either directly block the bone-resorptive cell or do so indirectly via cytokine arrest. Despite these advances, a substantial number of patients with inflammatory arthritis remain resistant to current therapies, and even effective anti-inflammatory drugs frequently do not repair damaged bone. Thus, insights into events such as those impacted by inflammasomes, which signal through cytokine-dependent and -independent mechanisms, are needed to optimize treatment of inflammatory osteolysis.. ...
There are many causes of inflammatory osteolysis, but regardless of etiology and cellular contexts, the osteoclast is the bone-degrading cell. Thus, the impact of inflammatory cytokines on osteoclast formation and function was among the most important discoveries advancing the treatment of focal osteolysis, leading to development of therapeutic agents that either directly block the bone-resorptive cell or do so indirectly via cytokine arrest. Despite these advances, a substantial number of patients with inflammatory arthritis remain resistant to current therapies, and even effective anti-inflammatory drugs frequently do not repair damaged bone. Thus, insights into events such as those impacted by inflammasomes, which signal through cytokine-dependent and -independent mechanisms, are needed to optimize treatment of inflammatory osteolysis.. ...
A number of inflammatory cytokines may contribute to the periarticular bone loss of RA, but the most significant is TNF-α. Macrophages and T cells express TNF-α in the arthritic synovial tissue as a membrane-residing protein that does not promote osteoclast formation until it is cleaved to its soluble form (40). Like RANKL, TNF-α exerts its biological effects by clustering and trimerizing three monomeric receptors (41). In fact, TNF-α activates two known receptor complexes, namely TNF receptor type 1 (TNFR1) and type 2 (TNFR2), and each prompts different intracellular events. TNFR1, which is principally stimulated by soluble TNF-α, transmits proinflammatory signals and synergizes with RANK to promote osteoclastogenesis (42). Signals induced by TNFR2, which largely recognizes membrane-residing TNF-α, are pro-immunogenic and anti-inflammatory (43). Thus, TNFR1 is responsible for the crippling effects of RA, PsA, and other forms of focal osteolysis, such as that complicating orthopedic ...
TY - CHAP. T1 - Osteoclasts. T2 - Potential target for blocking microenvironmental support of myeloma. AU - Galson, Deborah L.. AU - DSouza, Sonia. AU - Roodman, G. David. PY - 2013/1/1. Y1 - 2013/1/1. N2 - Multiple myeloma (MM) bone disease is a major contributor to the morbidity and mortality of MM patients due to pathological fractures. The MM cells interact with the cells of the bone microenvironment to both generate bone lesions as a result of enhanced induction of osteoclastogenesis and prevent reactive new bone formation to heal the lesions by repressing osteoblast activity. The MM stimulated osteoclasts (OCLs) not only generate bone lesions, but also interact with the myeloma cells to promote the proliferation and survival of the MM cells through the generation of interleukin-6 (IL-6), osteopontin, fibroblast activation protein, BAFF, APRIL, and annexin II. These MM-supportive OCL products present therapeutic opportunities. Further, the enhanced bone resorption by OCLs releases ...
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays a crucial role in bone remodeling through altering the interplay between bone-forming osteoblasts and bone-resorbing osteoclasts. While effects of AhR signaling in osteoblasts are well understood, the role and mech …
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays a crucial role in bone remodeling through altering the interplay between bone-forming osteoblasts and bone-resorbing osteoclasts. While effects of AhR signaling in osteoblasts are well understood, the role and mech …
In an aging society, it can be foreseen that the incidence of diseases associated with undesired bone loss, such as metastatic bone disease, rheumatoid arthritis, osteoporosis, and periodontitis, will increase considerably. Thus, drugs specifically targeting osteoclasts and their activity are desirable, possibly as supplementary agents to existing therapies. Orally applicable Src inhibitors could be advantageous compared with the widely used bisphosphonates because the latter can cause complications in the upper gastrointestinal tract (15) or can lead to osteonecrosis of the jaw (16). Indeed, the Src inhibitor CGP76030 was shown to reduce the number of osteoclasts in rat tibiae more efficiently than the bisphosphonate alendronate (18). Little is known, however, of the effect of Src inhibitors on human osteoclasts. Here, we describe the effect of Src inhibitor AZD0530 on osteoclast formation and activity in the different models used (osteoblast/PBMC cocultures, PBMCs cultured at high density ...
Shop Osteoclast-associated immunoglobulin-like receptor ELISA Kit, Recombinant Protein and Osteoclast-associated immunoglobulin-like receptor Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
Histone acetyltransferases of the MYST family are recruited to chromatin by BRPF scaffolding proteins. We explored functional consequences and the therapeutic potential of inhibitors targeting acetyl-lysine dependent protein interaction domains (bromodomains) present in BRPF1-3 in bone maintenance. We report three potent and selective inhibitors: one (PFI-4) with high selectivity for the BRPF1B isoform and two pan-BRPF bromodomain inhibitors (OF-1, NI-57). The developed inhibitors displaced BRPF bromodomains from chromatin and did not inhibit cell growth and proliferation. Intriguingly, the inhibitors impaired RANKL-induced differentiation of primary murine bone marrow cells and human primary monocytes into bone resorbing osteoclasts by specifically repressing transcriptional programs required for osteoclastogenesis. The data suggest a key role of BRPF in regulating gene expression during osteoclastogenesis, and the excellent druggability of these bromodomains may lead to new treatment strategies for
Breast cancer is a major public health issue for women worldwide and 70% of the disease preferentially metastasizes to bone resulting in its destruction. Advanced breast cancer releases osteoclastogenic factors to promote bone resorption. As bone metastasis with breast cancer is associated with high mortality, osteoclastogenesis is a potential therapeutic target. We have shown previously that benzyl isothiocyanate (BITC), which is present in edible cruciferous vegetables, inhibits breast cancer development in a transgenic mouse model. The present study was designed to determine effect of BITC on breast cancer-induced osteoclastogenesis. We employed well-established in vitro osteoclast co-culture system of Raw 264.7 murine macrophage cells with human breast cancer cells for this assessment. BITC treatment significantly inhibited the number as well as size of osteoclasts in a dose dependent manner in every co-culture experiment. In addition, BITC downregulated both mRNA and protein levels of ...
In this report we investigated the role of the newly described TNF-related protein, OPGL, in OC activation. Previously, Lacey et al. (1998) and Yasuda et al. (1998b) identified OPGL/ODF as the long sought OC differentiation factor. Direct expression cloning was used independently by the two groups to identify OPGL/ODF as the ligand for OPG/OCIF. OPG is expressed only as a soluble form and is now believed to act as a soluble decoy receptor to regulate the action of OPGL on differentiation of OCs. The data presented in the two reports provide strong evidence that OPGL acts directly on a population of OC progenitors, and together with CSF-1 induces terminal differentiation into mature, active OCs. Our data also showed that OPGL activated mature OCs to resorb bone in vitro (Lacey et al., 1998), and recent work supports our previous results (Fuller et al., 1998).. In this report we have shown that OPGL or agonist antibodies to its receptor, RANK, act directly on fully differentiated, mature OCs ...
c-Src and Lyn will be the only Src family kinases (SFKs) with established activity in osteoclasts (OCs). RANK Gandotinib ligand (RANKL)-induced differentiation attended by suppressed activation of the osteoclastogenic signaling molecules c-Jun and NF-κB. The anti-apoptotic properties of RANKL are also compromised in cells deleted of Fyn an event mediated by increased Bim expression and failed activation of Akt. The defective osteoclastogenesis of Fyn-/- OCs dampens bone resorption in vitro. Finally while Fyn deficiency does not regulate basal osteoclastogenesis in vivo it reduces that stimulated by RANKL by approximately 2/3. Thus Fyn is usually a pro-resorptive SFK which exerts its effects by prompting proliferation and differentiation while attenuating apoptosis of OC lineage cells. Keywords: Gandotinib Osteoclasts Fyn Src family kinase (SFK) M-CSF RANK ligand OCs are multinucleated hematopoietic cells with the unique capacity to degrade bone. They are generated under the aegis of M-CSF and ...
Vitamin D3, and its most active form 1,25(OH)2D3, are well known to stimulate osteoclastogenesis through stromal cell induction of the receptor activator of nuclear factor kappaB ligand (RANKL). Mitogen activating protein kinase phosphatase-1 (MKP-1) is a phosphatase classically known to negatively regulate the immune response through dephosphorylation of p38, ERK, and JNK activity. Objective: The purpose of this study was to define the role of MKP-1 in genomic 1,25(OH)2D3 signaling and downstream osteoclastogenesis through RANKL. Methods: Primary bone marrow stromal cells (BMSCs) from tibias and femurs of MKP-1-/- and MKP-1+/+ mice were collected. Gene expression was measured using RT-qPCR, protein expression by immunoblot and ELISA in 1,25(OH)2D3 treated cultures. Co-culture osteoclastogenesis assays were conducted as well. Results: RT-qPCR and immunoblot analysis comparing BMSCs revealed that 1,25(OH)2D3-induced VDR, CYP24a1 and RANKL mRNA expression and protein were significantly attenuated ...
TY - JOUR. T1 - T cell-mediated increased osteoclast formation from peripheral blood as a mechanism for crohns disease-associated bone loss. AU - Oostlander, A.E.. AU - Everts, V.. AU - Schoenmaker, T.. AU - Bravenboer, N.. AU - van Vliet, S.J.. AU - van Bodegraven, A.A.. AU - Lips, P.T.A.M.. AU - Vries, T.J.. PY - 2012. Y1 - 2012. U2 - 10.1002/jcb.23352. DO - 10.1002/jcb.23352. M3 - Article. C2 - 21898548. VL - 113. SP - 260. EP - 268. JO - Journal of Cellular Biochemistry. JF - Journal of Cellular Biochemistry. SN - 0730-2312. IS - 1. ER - ...
Fingerprint Dive into the research topics of Disordered osteoclast formation in RAGE-deficient mouse establishes an essential role for RAGE in diabetes related bone loss. Together they form a unique fingerprint. ...
Osteoclast[edit]. Osteoclasts are very large multinucleate cells that are responsible for the breakdown of bones by the process ... Bone is constantly remodelled by the resorption of osteoclasts and created by osteoblasts.[12] Osteoclasts are large cells with ... and can bind to receptors on osteoclasts to directly inhibit osteoclast activity. Osteoprotegerin is secreted by osteoblasts ... Osteoblasts and osteocytes are involved in the formation and mineralization of bone; osteoclasts are involved in the resorption ...
Chappard D, Alexandre C, Riffat G (1983). "Histochemical identification of osteoclasts. Review of current methods and ...
Osteoclasts break down bone tissue, and along with osteoblasts and osteocytes form the structural components of bone. In the ... Osteoclasts are multinucleated cells that derive from hematopoietic progenitors in the bone marrow which also give rise to ... Loutit, J.F.; Nisbet, N.W. (January 1982). "The Origin of Osteoclasts". Immunobiology. 161 (3-4): 193-203. doi:10.1016/S0171- ... Jones, S.J.; Boyde, A. (December 1977). "Some morphological observations on osteoclasts". Cell and Tissue Research. 185 (3): ...
Osteoclasts are generally present on the outer layer of bone, just beneath the periosteum. Attachment of the osteoclast to the ... Calcitonin decreases osteoclast activity, and decreases the formation of new osteoclasts, resulting in decreased resorption. ... The osteoclast then induces an infolding of its cell membrane and secretes collagenase and other enzymes important in the ... The osteoclasts are multi-nucleated cells that contain numerous mitochondria and lysosomes. These are the cells responsible for ...
PGE2 upregulates bone resorption by osteoclasts and their levels are higher in patients with periodontal disease than in ... "Osteoclasts - Wheeless' Textbook of Orthopaedics". Wheelessonline.com. 2012-06-01. Retrieved 2015-05-06. "Subantimicrobial Dose ... This dosage of doxycycline has cytokine and osteoclasts inhibitory action rather than being antimicrobial. Enamel Matrix ...
Osteoclasts are multinucleated giant cells. They are found in Howship's lacunae. Bone is lost through the process of resorption ... The resorption phase lasts as long as the lifespan of the osteoclast which is around 8 to 10 days. After this resorption phase ... The cellular component of bone consists of osteoblasts, osteocytes and osteoclasts. Osteoblasts are usually cuboidal and ... Bar-Shavit Z (December 2007). "The osteoclast: a multinucleated, hematopoietic-origin, bone-resorbing osteoimmune cell". ...
Many believed osteoclasts and osteoblasts came from the same progenitor cell. Because of this, osteoclasts were thought to be ... Non-osteoclast MGCs can arise in response to an infection, such as from tuberculosis, herpes, or HIV, or foreign body. These ... Osteoclasts are the most prominent examples of MGCs and are responsible for the resorption of bones in the body. Like other ... Osteoclasts were discovered in 1873. However, it wasn't until the development of the organ culture in the 1970's that their ...
Syncytin-1 is a Class I fusogen involved in the fusion of cells to form osteoclasts in humans. During the early actions of ... Osteoclasts are multinucleated bone-resorbing cells. They are formed by the fusion of differentiated monocytes, much like ... However, the molecules that induce fusion-competence in macrophages that are destined to become osteoclasts are different from ... For instance, transcription factor NFATC1 regulates genes that are specific to osteoclast differentiation. Zygote formation is ...
CT works by activating the G-proteins Gs and Gq often found on osteoclasts, on cells in the kidney, and on cells in a number of ... Nishikawa T, Ishikawa H, Yamamoto S, Koshihara Y (September 1999). "A novel calcitonin receptor gene in human osteoclasts from ... Chambers TJ, Magnus CJ (January 1982). "Calcitonin alters behaviour of isolated osteoclasts". The Journal of Pathology. 136 (1 ... "Regulation of calcitonin receptor by glucocorticoid in human osteoclast-like cells prepared in vitro using receptor activator ...
In contrast, osteoclasts break down bone tissue to increase blood calcium levels if they are low. This activity is performed ... In animals, eldecalcitol inhibits the activity of osteoclasts for the function to reduce bone degradation for calcium, while ... Matsuo K, Irie N (May 2008). "Osteoclast-osteoblast communication". Archives of Biochemistry and Biophysics. 473 (2): 201-9. ... where the body constantly maintains this calcium homeostasis through osteoblast and osteoclast activity. Osteoblast activity ...
RANKL activates osteoclasts, which resorb bone. The resultant bone lesions are lytic (cause breakdown) in nature, and are best ... Additional findings may include a raised calcium level (when osteoclasts are breaking down bone, releasing it into the ...
For instance, PTH also indirectly stimulates osteoclasts. However, the main effect of PTH is to increase the rate at which the ... which in turn activates osteoclasts. Calcitriol acts in concert with parathyroid hormone (PTH) in all three of these roles. ... intestinal uptake causes bone to take up more calcium than it loses by hormonal stimulation of osteoclasts. Only when there are ...
Therefore, by inhibiting osteoclasts, it prevents osteoporosis. When tamoxifen was launched as a drug, it was thought that ... September 2007). "Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts". Cell. ... "Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival". The EMBO Journal. 27 (3): 535-45 ...
... lowers blood calcium and phosphorus mainly through its inhibition of osteoclasts. Osteoblasts do not have calcitonin ... localized to osteoclasts, the kidney, and regions of the brain, is a G protein-coupled receptor. It is coupled by Gs to ... Inhibits osteoclast activity in bones, which break down the bone Minor effect: Inhibits renal tubular cell reabsorption of Ca2+ ... "Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and autoradiographic characterization". J. Clin. Invest ...
Osteoclasts are the cells responsible for the resorption of the root surface. Osteoclasts can break down bone, cartilage and ... Damage to the periodontal ligament can lead to RANKL release activating osteoclasts. Osteoclasts in close proximity to the root ... Osteoprotegerin (OPG) is also secreted by osteoclasts and stromal cells; this inhibits RANKL and therefore osteoclast activity ... Tooth resorption, or root resorption, is the progressive loss of dentine and cementum by the action of osteoclasts. This is a ...
Specifically, OPN anchors osteoclasts to the surface of bones where it is immobilized by its mineral-binding properties ... Osteoclast Fujisawa R (2002). "[Recent advances in research on bone matrix proteins]". Nippon Rinsho. 60. Suppl 3: 72-8. PMID ... OPN serves to initiate the process by which osteoclasts develop their ruffled borders to begin bone resorption. OPN contains ... Reinholt FP, Hultenby K, Oldberg A, Heinegård D (June 1990). "Osteopontin--a possible anchor of osteoclasts to bone". Proc. ...
Dougall WC (January 2012). "Molecular pathways: osteoclast-dependent and osteoclast-independent roles of the RANKL/RANK/OPG ... another regulator of osteoclastogenesis in osteoclast precursor cells and an autocrine signal for mature osteoclast cell death ... Mature osteoclasts then bind to bone through tight junctions and release digestive enzymes to resorb the old bone. As bone is ... During resorption osteoclasts release nutrients such as growth factors and calcium from the mineralised bone matrix which ...
TRAP is associated with osteoclast migration to bone resorption sites, and, once there, TRAP is believed to initiate osteoclast ... In osteoclasts, ROS are generated at the ruffled border and seem to be required for resorption and degradation to occur. In the ... Modulation of osteoclast adhesion in vitro". J. Biol. Chem. 269 (21): 14853-6. PMID 8195113. Darden AG, Ries WL, Wolf WC, ... In osteoclasts, TRAP is localized within the ruffled border area, the lysosomes, the Golgi cisternae and vesicles. Mammalian ...
NOTCH2 is also shown to regulate RANK-L osteoclastogenesis, which is the production of functional osteoclasts. Osteoclasts are ...
If the fracture gap is 800 μm to 1 mm, the fracture is filled by osteoclasts and then by lamellar bone oriented perpendicular ... In this case, cutting cones, which consists of osteoclasts, form across the fracture lines, generating cavities at a rate of 50 ... The trabecular bone is first resorbed by osteoclasts, creating a shallow resorption pit known as a "Howship's lacuna". Then ... IL-6 promotes differentiation of osteoblasts and osteoclasts. All cells within the blood clot degenerate and die. Within this ...
Vibrations from travel also break down the osteoclasts. A group of individuals launched a campaign on the website Experiment. ...
1996) Human osteoclast formation and bone resorption by monocytes and synovial macrophages in rheumatoid arthritis. Ann Rheum ... With TJ Chambers he developed the osteoclast lacunar bone resorption assay system. His work was the first to show that the ... His work on hip and knee implants focused on the importance of biomaterial wear particles on promoting osteoclast formation, ... 1984). Resorption of bone by isolated rabbit osteoclasts. J Cell Science 66: 383 - 399 PMID 6746762 Athanasou NA, Quinn J. ( ...
MafB gene activation suppresses the formation of osteoclasts. Thus, upregulation of LAP diminishes the number of osteoclasts, ... Inhibition of the expression of mTOR can stop osteoclast activity. CCAAT/enhancer-binding proteins are often involved in growth ...
... osteoclast recruitment and osteoclast function. This type of drug has a high affinity for hydroxyapatite and stays in bone ... The inhibition of osteoclast differentiation and function, precipitated by drug therapy, leads to decreased bone resorption and ... It inhibits osteoclast differentiation and activation, reduces bone resorption, improves bone density and lessens skeletal- ... It is also thought that bisphosphonates bind to osteoclasts and interfere with the remodeling mechanism in bone. To be more ...
Bones are made of cells called osteoclasts and osteoblasts. Two different kinds of bone resorption are possible: direct ...
CB2 receptors were expressed in osteoblasts, osteocytes, and osteoclasts. The selective CB2 agonist HU-308, but not the CB1 ... increased numbers of osteoclasts, and decreased numbers of diaphyseal osteoblast precursors. ... attenuated ovariectomy-induced bone loss and markedly stimulated cortical thickness through the suppression of osteoclast ... and activity of endocortical osteoblasts and restrained trabecular osteoclastogenesis by inhibiting proliferation of osteoclast ...
The function of osteoclasts depends on them for a variety of cellular processes like apoptosis. Bisphosphonates mimic the ... This does not concern other cells in the bone as this takes place by a selective uptake of osteoclasts. The common function ... Bisphosphonates reduce breakdown of bones by inhibiting osteoclasts, they have a long history of use and today there are a few ... The ATP analogue accumulates in the cytosol of the osteoclast with a cytotoxic effect. The primary mechanism of action of the ...
"Active NMDA glutamate receptors are expressed by mammalian osteoclasts". The Journal of Physiology. 518 (Pt 1): 47-53. doi: ...
Osteoclast physiology[edit]. In the 1980s and 90s the physiology of typical osteoclasts was studied in detail. With the ... The Life of Osteoclast. *Random42: Animation by Random42 Scientific Communication on the role of osteoclasts in bone remodeling ... An osteoclast is a large multinucleated cell and human osteoclasts on bone typically have five nuclei and are 150-200 µm in ... In bone, osteoclasts are found in pits in the bone surface which are called resorption bays, or Howships lacunae. Osteoclasts ...
Osteoclasts: They are large cells produced by the fusion (joining) of several smaller ones. Osteoclasts travel over the surface ... The cells of osteoclasts are equipped with engulfs bone fragments mechanism.. *Osteoclasts usually dissolve collagen enzymes. ... The process of bone breakdown and mineral uptake by the osteoclasts is known as resorption:. *The main function of osteoclasts ... home/health & living health center/osteoblast vs osteoclast center /osteoblast vs osteoclast article ...
... had no effect on the number of osteoclast progenitors, in vitro osteoclast differentiation, overall bone mass, or bone ... However, these reports conflict in their nomination of osteoblasts versus osteoclasts as the key producers of skeletal SLIT3 ... Taken in context, multiple lines of evidence were unable to identify the physiologic function of osteoclast-derived SLIT3, ... Similar results were observed with the deletion of SLIT3 in LysM-positive cells, including osteoclast lineage cells. Consistent ...
This picture shows a normal osteoclast. It is a large cell with separately identifiable, multiple nuclei. Osteoclasts are ... This picture shows a normal osteoclast. It is a large cell with separately identifiable, multiple nuclei. Osteoclasts are ...
Osteopontin--a possible anchor of osteoclasts to bone.. F P Reinholt, K Hultenby, A Oldberg, and D Heinegård ... A key event in bone resorption is the binding of osteoclasts to the mineral matrix of bone surfaces. A candidate for mediating ... The results thus support the hypothesis that osteoclasts when resorbing bone are anchored by osteopontin bound both to the ... The present study demonstrates that osteopontin is highly enriched at regions of the bone surface where osteoclasts are ...
It is known that the monocyte/macrophage lineage gives rise to osteoclasts (OCs) by the action of macrophage colony stimulating ... The understanding of how osteoclasts are generated and whether they can be altered by inflammatory stimuli is a topic of ... B. F. Boyce, "Advances in the regulation of osteoclasts and osteoclast functions," Journal of Dental Research, vol. 92, no. 10 ... Osteoclasts derived from monocyte/macrophage lineage after M-CSF and RANKL stimulation. Osteoclast precursors (preosteoclast) ...
Osteoclasts. Osteoclasts. - See:. - osteoblasts. - osteocytes. - Discussion:. - osteoclast is a large multinucleated cell that ... Membrane-bound carbonic anhydrases in osteoclasts.. Carbonic anhydrase II plays a major role in osteoclast differentiation and ... monocytes from the marrow or the blood serve as precursors of osteoclasts;. - osteoclasts are found in notches or indentations ... actual amount of bone resorbed is dependent upon number of osteoclasts present and each osteoclasts activity;. - although ...
"We observed osteoclasts resorbing bone beneath osteoid seams, and fragments of osteoid isolated in the bone marrow. This type ... Fluoride, Osteoclasts, & Bone Resoprtion:. "An iliac crest bone biopsy revealed an increased amount of thick unmineralized ... Fluoride & Osteoclasts. SOURCE: Fluoride Action Network , May 24, 2012 , By Michael Connett ... "Osteoclasts were readily seen eroding bone. . . . Bone fluoride analysis showed 18 times the normal level of fluoride, 1.8%. ...
An osteoclast is a large multinucleated cell and human osteoclasts on bone typically have five nuclei and are 150-200 µm in ... Osteoclasts are found on those surfaces of bone which are undergoing resorption. On such surfaces, the osteoclasts are seen to ... In bone, osteoclasts are found in pits in the bone surface which are called resorption bays, or Howships lacunae. Osteoclasts ... When osteoclast-inducing cytokines are used to convert macrophages to osteoclasts, very large cells that may reach 100 µm in ...
d) Osteoclast number per mm bone perimeter in cancellous bone of the distal femur of Osx1-Cre;RANKLf/f (n = 4) and RANKLf/f (n ... e) Osteoclast number per mm bone surface in cancellous bone of the distal femur of 6-month-old Dmp1-Cre;RANKLf/f (n = 4) and ... d) Osteoclast number per mm of cancellous bone surface in the distal femur of tail-suspended or grounded control RANKLf/f and ... Matrix-embedded cells control osteoclast formation.. Xiong J1, Onal M, Jilka RL, Weinstein RS, Manolagas SC, OBrien CA. ...
Osteoclast cells form from a hematopoietic stem cells called monocytes. Osteoclasts resorb bone by attaching to the bone ... Osteoclast differentiation and function,biological,biology supply,biology supplies,biology product ... Osteoclast cells form from a hematopoietic stem cells called monocytes. Osteoclasts resorb bone by attaching to the bone ... B-Bridges Osteoclast Culture Kit includes cryopreserved osteoclast precursor (OCP) cells from bone marrow and culture medium ...
We show that osteoclasts secrete netrin-1 to induce sensory nerve axonal growth in subchondral bone. Reduction of osteoclast ... osteoclasts or knockdown of Dcc reduces OA pain behavior. In particular, inhibition of osteoclast activity by alendronate ... CGRP+ sensory nerves in subchondral bone increased along with an increase in osteoclast activity and DRG neuron ... Moreover, we demonstrated a possible role for netrin-1 secreted by osteoclasts during aberrant subchondral bone remodeling in ...
Netrin-1 from osteoclasts induces axonal growth. (A) Microfluidics assay of osteoclast-conditioned medium promoting DRG neuron ... We show that osteoclasts secrete netrin-1 to induce sensory nerve axonal growth in subchondral bone. Reduction of osteoclast ... Netrin-1 secreted by osteoclasts and axonal growth. To examine the molecular mechanism by which osteoclasts regulate axonal ... We acknowledge that other mechanisms may exist for osteoclast activation-induced OA pain. For example, osteoclasts are believed ...
Although CD44 is one known receptor for HA, antibodies that block CD44 had no effect on the inhibition of osteoclast formation ... show that high molecular mass HA (HMM-HA), but not low molecular mass HA, inhibited osteoclast differentiation of bone marrow- ... Hyaluronan inhibits osteoclast differentiation via Toll-like receptor 4. J. Cell Sci. 120, 166-176 (2007). [Abstract] [Full ...
Osteoclast stimulatory transmembrane protein is a protein that in humans is encoded by the OCSTAMP gene. GRCh38: Ensembl ... "Entrez Gene: Osteoclast stimulatory transmembrane protein". Retrieved 2016-07-24. CS1 maint: discouraged parameter (link) v t e ...
Methodology/Principal Findings Using in vitro cell systems, we show here that mature osteoclasts, but not their precursors, ... Conclusions/Significance We conclude that, in vitro mature osteoclasts control osteoblast chemotaxis via PDGF-bb/PDGFR-β ... Our subsequent functional analyses demonstrate that mature osteoclasts, whose platelet-derived growth factor bb (PDGF-bb) ... This may provide one key mechanism by which osteoclasts control bone formation in vivo. ...
... we previously performed a survey of tropomyosin isoforms in resting and resorbing osteoclasts. Osteoclasts were found to ... A, Osteoclasts were generated from murine bone marrow cultures and assayed by immunoblot for HMW Tm-2/3 and β-actin as a ... C, Confocal images of osteoclasts on glass or bone demonstrates the diffuse distribution of Tm-2/3 at the cell base and their ... Osteoclasts, which undergo rounds of polarization and depolarization as they progress through the resorptive cycle, possess an ...
Osteoclast differentiation [ Pathway menu , Organism menu , Pathway entry , Download KGML , Show description , User data ... The osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone ... from RANK changes gene expression patterns through transcription factors like NFATc1 and characterizes the active osteoclast. ...
Supporting these results, Nef-transgenic mice exhibit an increased osteoclast density and bone defects, and osteoclasts derived ... HIV-1 exacerbates osteoclast functions. Brigitte Raynaud-Messina, Lucie Bracq, Maeva Dupont, Shanti Souriant, Shariq M. Usmani ... HIV-1 exacerbates osteoclast functions. Brigitte Raynaud-Messina, Lucie Bracq, Maeva Dupont, Shanti Souriant, Shariq M. Usmani ... Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss. Brigitte Raynaud-Messina, Lucie Bracq ...
Similar numbers of osteoclasts were observed in both cultures and the cell size and number of nuclei per osteoclast were ... The osteoclasts were able to attach to the calcium phosphate layer on the BAG surface and were able to actively resorb it (Figs ... As osteoclasts are able to resorb calcium phosphates and HA materials, it is expected that they are also able to resorb at ... Resorption by osteoclasts did not completely remove the calcium phosphate layer on the BAG surface. a A SEM image of two ...
"Infliximab acts directly on human osteoclast precursors and enhances osteoclast formation induced by receptor activator of ... S. L. Teitelbaum and F. P. Ross, "Genetic regulation of osteoclast development and function," Nature Reviews Genetics, vol. 4, ... Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis. Inês P. Perpétuo,1 Joana ... L. K. Osier, S. N. Popoff, and S. C. Marks Jr., "Osteopetrosis in the toothless rat: failure of osteoclast differentiation and ...
These results show that FBGCs have the capacity to dissolve the mineral phase of bone, similar to osteoclasts. However, they ... Despite similarities, an important distinction between these cell types is that osteoclasts can resorb bone, but it is unknown ... Both cell types were cultured on bovine bone slices and analyzed for typical osteoclast features, such as bone resorption, ... At the gene expression level, FBGCs and osteoclasts expressed similar levels of mRNAs that are associated with the dissolution ...
Crystal structure of human osteoclast stimulating factor. Tong, S., Zhou, H., Gao, Y., Zhu, Z., Zhang, X., Teng, M., Niu, L.. ( ... Osteoclast-stimulating factor 1. A, B. 222. Homo sapiens. Mutation(s): 1 Gene Names: OSTF1. ...
G. An, C. Acharya, X. Feng, K. Wen, M. Zhong, L. Zhang, N. C. Munshi, L. Qiu, Y.-T. Tai, K. C. Anderson, Osteoclasts promote ... Osteoclast precursors, RANKL/RANK, and immunology. Authors. *. Lianping Xing,. Corresponding author. * Department of Pathology ... In contrast, study of the regulation of osteoclast precursors (OCPs) has been relatively slow, in part because it has been hard ... These findings suggest that OCPs may serve as a source for both osteoclasts and other effector cells and participate actively ...
An osteoclast is a specialized cell that absorbs and removes bone, allowing for the development of new bone, as defined in the ... Osteoclast Definition. An osteoclast is a specialized cell that absorbs and removes bone, allowing for the development of new ... Osteoporosis can occur when osteoclast activity outperforms osteoblast activity so more bone is taken up rather than being laid ...
Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable ... Impaired Differentiation of Osteoclasts in TREM-2-deficient Individuals. Marina Cella, Cecilia Buonsanti, Carey Strader, ... PYK2 in osteoclasts is an adhesion kinase, localized in the sealing zone, activated by ligation of alpha(v)beta3 integrin, and ... Impaired Differentiation of Osteoclasts in TREM-2-deficient Individuals. Marina Cella, Cecilia Buonsanti, Carey Strader, ...
Osteoclast differentiation - Mus musculus (mouse) [ Pathway menu , Organism menu , Pathway entry , Download KGML , Show ... The osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone ... from RANK changes gene expression patterns through transcription factors like NFATc1 and characterizes the active osteoclast. ...
Safety Study of Maravirocs Effect on Human Osteoclasts (MVC-Bone). The safety and scientific validity of this study is the ...
... were used to test the hypothesis that tartrate-resistant acid phosphatase might serve as a biochemical marker for osteoclast ... Holtrop, M. E., Raisz, L. G., King, G. J.: The response of osteoclasts to prostaglandin and osteoclast activating factor as ... Hall, B. K.: The origin and fate of osteoclasts, Anat. Rec.183:1-12, 1975CrossRefPubMedGoogle Scholar ... Acid phosphatase, tartrate-resistant Isoenzymes Bone resorption Osteoclast This is a preview of subscription content, log in to ...
... Nat Med. 2012 Feb ... Mice deficient in either Wnt5a or Ror2, and those with either osteoclast precursor-specific Ror2 deficiency or osteoblast- ... Wnt5a-Ror2 signals enhanced receptor activator of nuclear factor-κB (RANK) expression in osteoclast precursors by activating ... We showed that Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhanced osteoclastogenesis. ...
  • These membrane-bound proteins are produced by neighbouring stromal cells and osteoblasts , thus requiring direct contact between these cells and osteoclast precursors . (wikipedia.org)
  • Osteoclast precursors (preosteoclast) are M-CSF-dependent for proliferation and respond to RANKL through its receptor. (hindawi.com)
  • The cytokine receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast formation and thought to be supplied by osteoblasts or their precursors, thereby linking bone formation to resorption. (nih.gov)
  • Osteoclasts were found to express two closely related tropomyosins of the high molecular weight type, which are not expressed in monocytic and macrophage precursors. (nih.gov)
  • Effect of tumor necrosis factor inhibitor therapy on osteoclasts precursors in ankylosing spondylitis," PLoS ONE , vol. 10, no. 12, Article ID e0144655, 2015. (hindawi.com)
  • In contrast, study of the regulation of osteoclast precursors (OCPs) has been relatively slow, in part because it has been hard to accurately identify them. (wiley.com)
  • Osteoblast-lineage cells expressed Wnt5a, whereas osteoclast precursors expressed Ror2. (nih.gov)
  • Wnt5a-Ror2 signals enhanced receptor activator of nuclear factor-κB (RANK) expression in osteoclast precursors by activating JNK and recruiting c-Jun on the promoter of the gene encoding RANK, thereby enhancing RANK ligand (RANKL)-induced osteoclastogenesis. (nih.gov)
  • In line with the lack of a bone phenotype, the levels of AR were very low in osteoclast-enriched cultures derived from bone marrow (BM) and undetectable in osteoclasts generated from spleen precursors. (sigmaaldrich.com)
  • In vitro studies employing NaPi-IIa-deficient osteoclast precursors and mature osteoclasts reveal that NaPi-IIa is dispensable for bone resorption and osteoclast differentiation. (nih.gov)
  • By contrast, both type III sodium-dependent phosphate transporters Pit-1 and Pit-2 were abundantly expressed throughout osteoclast differentiation, indicating that they are the relevant sodium-dependent phosphate transporters in osteoclasts and osteoclast precursors. (nih.gov)
  • Kindlin3 is expressed solely in hematopoietic cells, including osteoclasts and their precursors. (osu.edu)
  • These data further showed that overexpression of the F2 and PH domains together in osteoclast precursors inhibited their differentiation. (osu.edu)
  • This could provide important clues to our understanding on how osteoclast precursors are primed within the circulation whilst commuting to the site of ultimate osteoclast differentiation. (uva.nl)
  • Treating bone marrow macrophages with lower doses of the PKD inhibitors had little effect on M-CSF + RANKL-dependent induction into committed osteoclast precursors, but inhibited their motility and subsequent differentiation into multinucleated mature osteoclasts, whereas higher doses of the PKD inhibitors induced apoptosis of the preosteoclasts. (mdpi.com)
  • Using an inducible knockout mouse model to generate dynamin 1- and 2-deficient primary osteoclast precursors and myoblasts, we found that fusion of both cell types requires dynamin. (rupress.org)
  • Since dynamin is involved in both the formation of actin-rich structures and in endocytosis, our results indicate that dynamin function is central to the osteoclast precursors and myoblasts fusion process, and point to an important role of endocytosis in cell-cell fusion. (rupress.org)
  • have been identified and characterized, little is known about fusogens in osteoclast precursors (OCPs) and myoblasts cell fusion. (rupress.org)
  • Osteoclasts derive from monocyte/macrophage precursors and are unrelated to osteoblasts. (thefreedictionary.com)
  • Osteoclasts are bone-resorbing cells that differentiate from macrophage precursors in response to receptor activator of NF-κB (RANKL). (pubmedcentralcanada.ca)
  • In the present study we have identified osteoclast precursors among clones of RAW264.7 cells. (pubmedcentralcanada.ca)
  • Objectives Given that high levels of CXCR4 are associated with RA pathogenesis, we sought to determine whether CXCR4 levels are altered by adalimumab (ADA) both in vivo in RA patients and in the human TNF transgenic mouse model (huTNF Tg197) of arthritis, as well as in vitro with RA fibroblast-like synoviocytes (RA-FLS) and human osteoclast precursors (OCP) following TNF exposure. (bmj.com)
  • They were phenotypically and functionally characterised by flow cytometric and gene expression analysis, as well as in in vitro cocultures with osteoclast precursors. (bmj.com)
  • This research project in Dr. Westendorf's lab focuses on the signaling pathways that are impacted by altering Wnt signaling in osteoclast precursors or in osteoblasts. (mayo.edu)
  • Here we show that exosomes isolated from the murine prostate cancer cell line TRAMP-C1 dramatically decrease fusion and differentiation of monocytic osteoclast precursors to mature, multinucleated osteoclasts. (diva-portal.org)
  • Platelet-rich plasma impairs osteoclast generation from human precursors of peripheral blood. (semanticscholar.org)
  • The OCPs then home to the inflamed joints to differentiate into mature osteoclasts or to produce more inflammatory factors in the presence of RANKL. (wiley.com)
  • 93: 165-176), but their effects on mature osteoclasts are not well understood. (rupress.org)
  • Mature osteoclasts are not typically found in the vasculature. (fightaging.org)
  • Generation of hematopoietic myeloid progenitors and mature osteoclasts from human ES cell lines. (labome.org)
  • We will test the conditions to insert specific genes in hES cells with restricted expression in the myeloid system, including mature osteoclasts. (labome.org)
  • The results revealed that Dlx1 and Dlx2 are the only Dlx family members with a possible function in osteoclastogenesis as well as in mature osteoclasts. (whiterose.ac.uk)
  • RANKL plays a crucial role for the commitment to osteoclast lineage and the fusion of committed cells to achieve multinucleated feature of mature osteoclasts. (biologists.org)
  • Bisphosphonates exert an inhibitory action on mature osteoclasts and suppress bone resorption enhanced by metastatic tumor cells by inducing apoptosis of osteoclasts ( 12 , 13 ). (aacrjournals.org)
  • Lipopolysaccharide (LPS), a major constituent of Gram-negative bacteria, has been suggested to be a survival factor of mature osteoclasts via Toll-like receptor 4. (nii.ac.jp)
  • We investigated the distribution and function of EP receptors in human mature osteoclasts. (jrheum.org)
  • C1 co-localized with microtubules in the plasma membrane and its vicinity in mature osteoclasts. (biochemj.org)
  • however, the co-localization chiefly shifted to the cell periphery of mature osteoclasts. (biochemj.org)
  • Conditional deletion of SLIT3 in cathepsin K (CTSK)-positive cells, including osteoclasts, had no effect on the number of osteoclast progenitors, in vitro osteoclast differentiation, overall bone mass, or bone resorption/formation parameters. (nature.com)
  • To clarify the cellular sources of SLIT3, we first examined Slit3 expression in parallel with other osteoclast makers using real-time PCR during in vitro osteoclastogenesis. (nature.com)
  • To our knowledge we were the first to observe actively resorbing osteoclasts on S53P4 bioactive glass surfaces, in vitro. (springer.com)
  • The results obtained from biochemical assays, histochemical observations, and polyacrylamide gel electrophoresis suggest that bone resorption in vitro results in the release of tartrate-resistant acid phosphatase from osteoclasts and tartrate-sensitive acid phosphatase from other bone cells as well as osteoclasts. (springer.com)
  • Hepatocyte growth factor is a coupling factor for osteoclasts and osteoblasts in vitro. (uniprot.org)
  • Osteoclast generation and activity in vitro were similar between ARKO and wildtype control (WT) mice. (sigmaaldrich.com)
  • Recent literature indicates that osteoclast formation in vitro from peripheral blood of patients with diseases associated with bone loss such as rheumatoid arthritis, osteoporosis, periodontitis and bone metastatic cancer may occur spontaneously being independent of addition of osteoclast formation stimulating factors such as macrophage colony forming factor (M-CSF) and receptor activator of NFκB ligand (RANKL). (uva.nl)
  • Finally, there is evidence demonstrating that osteoclasts can be generated in vitro from ES cells. (labome.org)
  • We will test the developing cells by phenotypic characterization followed by in vitro functional characterization From these progenitors we will subsequently test their potential to derive mature and functional osteoclasts in defined in vitro conditions. (labome.org)
  • I have done a literature search (1966-present) and the seminal article seems to be Boyde & Jones (1984) Resorption of dentine by isolated osteoclasts in vitro. (histosearch.com)
  • Measurements of total body myeloma cell number and osteoclast activating factor (OAF) production by bone marrow myeloma cells in vitro were made in 33 patients with plasma cell myeloma. (biomedsearch.com)
  • Our in vitro studies support that PODXL expression in osteoclast lineage cells reduces osteoclast differentiation. (labome.org)
  • In vitro models of osteoclast differentiation are principally based on primary cell culture, which are poorly suited to molecular and transgene studies due to the limitations associated with the use of primary macrophage. (pubmedcentralcanada.ca)
  • mTOR inhibitor and bone-targeted drugs break the vicious cycle between clear-cell renal carcinoma and osteoclasts in an in vitro co-culture model. (urotoday.com)
  • S100A7-downregulated cells had decreased osteoclast number and size as compared to the vector controls, and this decrease was associated with variations in IL-8 expression in in vitro cell cultures. (harvard.edu)
  • Together, these data demonstrates that the lack of Y1Rs stimulates the formation of larger multinucleated osteoclasts in vitro with reduced bone-resorbing activity, unveiling a novel therapeutic option for osteoclastic bone diseases based on Y1R-signalling ablation. (garvan.org.au)
  • Osteoclasts are derived from monocytic progenitor cells and experimentally differentiate from spleen and bone marrow cells in the simultaneous presence of macrophage colony-stimulating factor (M-CSF) and RANKL in vitro ( 16 ). (aacrjournals.org)
  • Its effect on formation and activity of human osteoclasts in vitro was determined in cocultures of human osteoblasts and peripheral blood mononuclear cells. (aacrjournals.org)
  • It has recently become possible to generate human osteoclasts in vitro , by incubation of peripheral blood mononuclear cells (PBMCs) in macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). (biomedcentral.com)
  • [10] Osteoclast formation requires the presence of RANKL (receptor activator of nuclear factor κβ ligand) and M-CSF (Macrophage colony-stimulating factor) . (wikipedia.org)
  • RANKL knockout mice exhibit a phenotype of osteopetrosis and defects of tooth eruption, along with an absence or deficiency of osteoclasts. (wikipedia.org)
  • Osteoclast differentiation is inhibited by osteoprotegerin (OPG), which is produced by osteoblasts and binds to RANKL thereby preventing interaction with RANK. (wikipedia.org)
  • It is known that the monocyte/macrophage lineage gives rise to osteoclasts (OCs) by the action of macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL), which induce cell differentiation through their receptors, c-fms and RANK, respectively. (hindawi.com)
  • Osteoclasts derived from monocyte/macrophage lineage after M-CSF and RANKL stimulation. (hindawi.com)
  • However, RANKL is expressed by a variety of cell types, and it is unclear which of them are essential sources for osteoclast formation. (nih.gov)
  • Osteoclast differentiation and function is controlled primarily by Macrophage Colony-Stimulating Factor (M-CSF) and Receptor for Activation of Nuclear Factor Kappa B Ligand (RANKL). (bio-medicine.org)
  • B-Bridges Osteoclast Culture Kit includes cryopreserved osteoclast precursor (OCP) cells from bone marrow and culture medium containing M-CSF and RANKL for researchers studying osteoporosis, bone reabsorbtion, or other bone metabolism disorders. (bio-medicine.org)
  • Reduction of osteoclast formation by knockout of receptor activator of nuclear factor kappa-B ligand (Rankl) in osteocytes inhibited the growth of sensory nerves into subchondral bone, dorsal root ganglion neuron hyperexcitability, and behavioral measures of pain hypersensitivity in OA mice. (jci.org)
  • show that high molecular mass HA (HMM-HA), but not low molecular mass HA, inhibited osteoclast differentiation of bone marrow-derived macrophages in response to macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). (sciencemag.org)
  • The action of RANKL expression by T cells has primarily been thought to regulate the activity of dendritic cells (DC) but not osteoclasts ( 40 ). (jimmunol.org)
  • Our studies reveal RANKL-induced differential expression of sodium-dependent phosphate transport protein IIa (NaPi-IIa) transcript and protein during osteoclast development, but no expression of the closely related NaPi-IIb and NaPi-IIc SLC34 family isoforms. (nih.gov)
  • RANKL is essential for the differentiation, activation, activity, and survival of osteoclasts ( 4 ). (jimmunol.org)
  • In particular, addition of fucoidan into the early stage osteoclast cultures significantly inhibited receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast formation, thus suggesting that fucoidan affects osteoclast progenitors. (mdpi.com)
  • These results collectively suggest that fucoidan inhibits osteoclastogenesis from bone marrow macrophages by inhibiting RANKL-induced p38, JNK, ERK and NF-κB activation, and by downregulating the expression of genes that partake in both osteoclast differentiation and resorption. (mdpi.com)
  • RAW264.7 cell were cloned by limiting dilution and induced to osteoclast differentiation by treatment with recombinant RANKL. (pubmedcentralcanada.ca)
  • Each of the clones expressed the osteoclast marker genes TRAP and cathepsin-K mRNA with RANKL treatment. (pubmedcentralcanada.ca)
  • Longan fruit increase bone mineral density in zebrafish and ovariectomized rat by suppressing RANKL-induced osteoclast differentiation. (bioportfolio.com)
  • bone mineral density in zebrafish and ovariectomized rat by suppressing RANKL-induced osteoclast differentiation. (bioportfolio.com)
  • The RANK/RANKL pathway is a critical step in osteoclast differentiation and we created an inducible RANK (iRANK) fusion protein which could be activated by a small molecule chemical inducer of dimerization (CID). (washington.edu)
  • We have previously reported transgenic medaka lines expressing the osteoclast-inducing factor receptor activator of nuclear factor κB ligand (Rankl) under control of a heat shock-inducible promoter. (biologists.org)
  • Forced Rankl expression resulted in ectopic osteoclast formation, as visualized by live imaging in fluorescent reporter lines. (biologists.org)
  • The differentiation of osteoclasts, cells specialized for bone resorption, is governed by two key factors, macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). (biologists.org)
  • They showed in an arthritis model that systemically activated T cells are sufficient to induce receptor activator of NF-κB ligand (RANKL), which binds to its corresponding receptor RANK on osteoclast precursor cells, which ultimately induces their differentiation into osteoclasts. (bmj.com)
  • It was shown that IL-17 induces RANKL expression by osteoblasts, which further promotes osteoclast maturation. (bmj.com)
  • 8) osteoclasts and enhanced surface area, possibly due to monocyte chemoattractant protein-1 (MCP-1) overexpression regulated by RANKL-signalling. (garvan.org.au)
  • Regulation of RANKL (receptor activator of nuclear factor κB ligand)-induced osteoclast differentiation is of current interest in the development of antiresorptive agents. (uzh.ch)
  • For osteoblasts and osteoclasts, factors called macrophage-colony stimulating factor (M-CSF) and RANK Ligand (RANKL) "decide" what each cell will become by activating various intracellular signaling pathways. (saveourbones.com)
  • By activating these pathways, M-CSF and RANKL regulate the expression of osteoclast- and osteoblast-specific genes. (saveourbones.com)
  • The mechanism by which cyanidin does this is by inhibiting a "receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclast differentiation and formation…and downregulated the expression of osteoclast differentiation marker genes. (saveourbones.com)
  • 1 In other words, cyanidin plays a role in the natural regulation of osteoclasts in the process of bone remodeling, inhibiting a key RANKL receptor at the appropriate time. (saveourbones.com)
  • Activated platelets positively regulate RANKL-mediated osteoclast differentiation. (semanticscholar.org)
  • Osteocytes affect bone remodeling by producing regulatory factors to influence the activity of osteoblasts and osteoclasts in response to endocrine signals including the blood level of vitamin D . Osteocytes can sense pressures or cracks in the bone and help to direct where osteoclasts will dissolve the bone. (medicinenet.com)
  • 9 However, in this report, osteoclasts, as opposed to osteoblasts, were nominated as a key source of SLIT3 to control coupling between osteoblasts and osteoclasts. (nature.com)
  • It is now known that both osteoblasts and osteoclasts express multiple P2 receptor subtypes, and the increasing number of nucleotide-induced effects reported to. (archives-ouvertes.fr)
  • In disease conditions, cell communication between osteoblasts and osteoclasts is perturbed. (biologists.org)
  • Balanced osteoclast and osteoblast activity is necessary for skeletal health, whereas unbalanced osteoclast activity causes bone loss in many skeletal conditions. (mdpi.com)
  • In this study, we have found that fucoidan, a sulfated polysaccharide extracted from brown seaweed, inhibited osteoclast differentiation. (mdpi.com)
  • However, these reports conflict in their nomination of osteoblasts versus osteoclasts as the key producers of skeletal SLIT3 and additionally offer conflicting data on the effects of SLIT3 on osteoclastogenesis. (nature.com)
  • Here, aiming to address this discrepancy, we found no observable SLIT3 expression during human or mouse osteoclastogenesis and the only modest SLIT3-mediated effects on osteoclast differentiation. (nature.com)
  • The understanding of how osteoclasts are generated and whether they can be altered by inflammatory stimuli is a topic of particular interest for osteoclastogenesis. (hindawi.com)
  • Mice deficient in either Wnt5a or Ror2, and those with either osteoclast precursor-specific Ror2 deficiency or osteoblast-lineage cell-specific Wnt5a deficiency showed impaired osteoclastogenesis. (nih.gov)
  • In co-culture experiments, BM stromal cells (BMSCs) were essential for the suppressive action of AR on osteoclastogenesis and osteoclast activity. (sigmaaldrich.com)
  • A central observation for osteoimmunology comes from the demonstration that skeletal homeostasis is dynamically influenced by the immune system and lymphocyte-derived cytokines are among the most potent mediators of osteoclast function and osteoclastogenesis ( 3 , 5 , 6 , 7 , 8 , 9 , 10 ). (jimmunol.org)
  • Osteoclastogenesis and osteoclast activity were detected with tartrate-resistant acid phosphatase staining, a pit formation assay, gelatin zymography, and a cathepsin K ELISA assay. (figshare.com)
  • AZD0530 was most effective in inhibiting osteoclast-like cell formation when present at the onset of osteoclastogenesis, suggesting that Src activity is important during the initial phase of osteoclast formation. (aacrjournals.org)
  • Less clear is fluoride's impact on bone resorption and the cells (osteoclasts) that resorb bone. (fluoridealert.org)
  • Osteoclasts resorb the mineralized matrices formed by chondrocytes or osteoblasts. (nih.gov)
  • Osteoclasts resorb bone by attaching to the bone surface and lowering the surrounding pH to an acidic level of around 4.5. (bio-medicine.org)
  • Bone is remodeled throughout the life of an animal by the action of osteoclasts, which resorb bone, and osteoblasts, which form new bone. (jimmunol.org)
  • To maintain steady-state bone mass, cells of the myeloid origin called osteoclasts resorb bone during remodeling. (jimmunol.org)
  • Overexpression of the F1, F2, F3 and PH domains individually affected the ability of osteoclasts to resorb bone. (osu.edu)
  • Osteoclasts are multinucleated giant cells of hematopoietic origin having a unique capacity to resorb the bone matrix. (frontiersin.org)
  • Our studies and the known functions of PODXL lead to our central hypothesis that early progenitor membrane expression levels of a PODXL membrane complex including CXCR4 and NHERF1 must be reduced to allow for precursor fusion and lower levels of this complex are required for activation of osteoclasts, enabling them to resorb bone. (labome.org)
  • Osteoclasts resorb mineral in vivo and we hypothesized that a cell therapy based on inducible osteoclast differentiation could be used as a cell therapy to treat EC and HO. (washington.edu)
  • Scale bar, 0.5 mm. ( f ) Histological sections of distal femurs of 5-week-old RANKLf/f and Prx1-Cre;RANKLf/f mice stained for tartrate-resistant acid phosphatase (TRAP) activity (osteoclasts stain red). (nih.gov)
  • To examine whether AR in osteoclasts directly suppresses bone resorption, we crossed AR-floxed with cathepsin K-Cre mice. (sigmaaldrich.com)
  • Osteoclast-specific ARKO (ocl-ARKO) mice showed no changes neither in osteoclast surface nor in bone microarchitecture nor in the response to orchidectomy and androgen replacement, indicating that the AR in osteoclasts is not critical for bone maintenance. (sigmaaldrich.com)
  • Since tibiae of ubiquitous ARKO mice displayed increased osteoclast counts, the role of AR was further explored using cell cultures from these animals. (sigmaaldrich.com)
  • Using transgenic OT-I mice, we found that in the presence of OVA, osteoclasts induced the secretion of IL-2, IL-6, and IFN-γ as well as the proliferation of CD8 + T cells. (jimmunol.org)
  • Mice homozygous for a knock-out allele exhibit defective osteoclast fusion but normal skeletal paramaters. (jax.org)
  • To address this difficulty we are now developing novel mouse models, the adult osteopetrotic mice, for studying the interplay between osteoclasts and osteoblasts. (nordforsk.org)
  • Reduced bone quality in Gnas +/p− mice was associated with increased endosteal osteoclast numbers, with no significant effects on osteoblast number and function. (nature.com)
  • Osteoclasts were prepared from three mice for each genotype. (sciencemag.org)
  • Osteoclast number per bone perimeter from control and Ror2 ΔOcl/ΔOcl mice. (sciencemag.org)
  • We will develop immunodeficient animals in which we will be able to eliminate osteoblasts and then test the ability of these mice to accept human hematopoietic grafts utilizing some of the reporter systems developed in aim 2 to track osteoclast development in vivo. (labome.org)
  • The authors used oc/oc mice, which a loss of osteoclast (OCL) activity, to investigate the role of osteoblasts (OBLs) and OCLs in the development of the hematopoietic stem cell (HSC) niche. (asbmr.org)
  • We have examined the vertebrae of mice in which the CD34 family member PODXL is deleted in hematopoietic/osteoclast lineage cells (hem lineage-PODXLdel mice). (labome.org)
  • We will comprehensively phenotype the hem lineage-PODXLdel mice, establish the effects of ovariectomy on bone metabolism in hem lineage-PODXLdel mice, define the impact of loss of PODXL in early osteoclast lineage cells during anabolic PTH treatment, and compare mice with PODXL deleted in late osteoclast lineage cells to the hem lineage-PODXLdel mice. (labome.org)
  • ARTD inhibited receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and bone resorbing activity by reducing the secreted levels of matrix metalloproteinase-9 and cathepsin K. Furthermore, ARTD prevented estrogen deficiency-induced bone loss in ovariectomized mice. (figshare.com)
  • Osteoblastic cells from transgenic mice constitutively expressing human IL-6R could support osteoclast development in the presence of human IL-6 alone in cocultures with normal spleen cells. (rupress.org)
  • In contrast, osteoclast progenitors in spleen cells from transgenic mice overexpressing human IL-6R were not able to differentiate into osteoclasts in response to IL-6 in cocultures with normal osteoblastic cells. (rupress.org)
  • The authors show that osteoclast-targeted deletion in mice of solute carrier family 4 anion exchanger member 2 (Slc4a2) results in osteopetrosis. (asbmr.org)
  • c-Src is indispensable for the formation of a sealing zone and subsequent ruffled border because osteoclasts from c-Src knockout mice lack the capacity to redistribute F-actin as ring-like structures ( 8 , 11 ). (aacrjournals.org)
  • This permits characterization of osteoclasts by their staining for high expression of tartrate resistant acid phosphatase (TRAP) and cathepsin K . Osteoclast rough endoplasmic reticulum is sparse, and the Golgi complex is extensive. (wikipedia.org)
  • Osteoclast formation was further monitored by tartrate-resistant acid phosphatase (TRAP) staining (Fig. 1a-c ). (nature.com)
  • Importantly, knockout of Netrin1 in tartrate-resistant acid phosphatase-positive (TRAP-positive) osteoclasts or knockdown of Dcc reduces OA pain behavior. (jci.org)
  • Organ cultures of newborn mouse calvaria were used to test the hypothesis that tartrate-resistant acid phosphatase might serve as a biochemical marker for osteoclast function. (springer.com)
  • We show that Caki-2 cells can induce osteoclast cells differentiation from isolated human monocytes, as demonstrated by specific tartrate-resistant acid phosphatase (TRAP) staining and f-actin ring formation, in a statistically significant manner. (urotoday.com)
  • Interestingly, functional studies revealed that these giant Y1R(-/-) multinucleated cells produce poorly demineralized eroded pits, which were associated to reduce expression of osteoclast matrix degradation markers, such as tartrate-resistant acid phosphatase-5b (TRAcP5b), matrix metalloproteinase-9 (MMP-9) and cathepsin-K (CTSK). (garvan.org.au)
  • Furthermore, in an osteoclast-like cell formation assay using mouse bone marrow cells, Ki20227 inhibited the development of tartrate-resistant acid phosphatase-positive osteoclast-like cells in a dose-dependent manner. (aacrjournals.org)
  • Moreover, Ki20227 decreased the number of tartrate-resistant acid phosphatase-positive osteoclast-like cells on bone surfaces in ovariectomized (ovx) rats. (aacrjournals.org)
  • These drugs function to either block bone resorption by osteoclasts or augment bone formation by osteoblasts. (nature.com)
  • Matrix-embedded cells control osteoclast formation. (nih.gov)
  • Although CD44 is one known receptor for HA, antibodies that block CD44 had no effect on the inhibition of osteoclast formation by HA. (sciencemag.org)
  • Rapid progress has been made in recent years in our understanding of the mechanisms regulating the formation, activation, and survival of osteoclasts, which are derived from precursor cells in the myeloid lineage. (wiley.com)
  • Induces bone resorption, acting probably through a signaling cascade which results in the secretion of factor(s) enhancing osteoclast formation and activity. (rcsb.org)
  • Studies of patients with osteopetrosis, a disease with too much bone mass often caused by defective bone resorption by the osteoclasts, have however indicated that bone formation is not only correlated to bone resorption. (nordforsk.org)
  • These studies indicate that osteoclasts produce a so far unknown factor leading to bone formation by the osteoblasts. (nordforsk.org)
  • Using unbiased global proteomics (study of proteins), the researchers were able to examine osteoclast-like cells in the vasculature to determine which proteins induced osteoclast formation. (fightaging.org)
  • Skeletal bone formation and maintenance requires coordinate functions of several cell types, including bone forming osteoblasts and bone resorbing osteoclasts. (nature.com)
  • C and D ) Effects of recombinant Wnt5a on the formation of resorption pits (hematoxylin staining) (C) and actin rings (D) by osteoclasts derived from wild-type (WT) and Wnt5a −/− liver macrophages on dentin slices. (sciencemag.org)
  • CLEC2D inhibits osteoclast formation, and by extension, bone resorption, and modulates the release of interferon-gamma. (thefreedictionary.com)
  • We show that PKD inhibitors CRT0066101 and CID755673 inhibit several distinct aspects of osteoclast formation. (mdpi.com)
  • In conclusion, these data implicate PKD kinases as positive regulators of osteoclasts, which are essential for multiple distinct processes throughout their formation and function. (mdpi.com)
  • Cell-cell fusion is an evolutionarily conserved process that leads to the formation of multinucleated myofibers, syncytiotrophoblasts and osteoclasts, allowing their respective functions. (rupress.org)
  • Osteoclast and myoblast cell-cell fusion involves the formation of actin-rich protrusions closely associated with clathrin-mediated endocytosis in the apposed cell. (rupress.org)
  • In multicellular organisms, cell-cell fusion is a highly evolutionarily conserved process that leads to the formation of multinucleated cells including myotubes, syncytiotrophoblasts, and osteoclasts. (rupress.org)
  • An osteoclast (blue, centre) is a giant multi-nucleated cell that normally breaks down the calcified matrix of bone (yellow) during bone growth and formation. (sciencephoto.com)
  • Multiple myeloma is characterized by the accumulation of clonal malignant plasma cells in the bone marrow, which stimulates bone destruction by osteoclasts and reduces bone formation by osteoblasts. (aacrjournals.org)
  • Osteoclasts promote the formation of hematopoietic stem cell niches in the bone marrow. (asbmr.org)
  • Ideally, new therapy targets to reduce osteoclast-mediated bone loss will block osteoclasts while also preserving bone formation. (labome.org)
  • This may be challenging since evidence is mounting that osteoclasts, whether or not they are capable of resorbing bone, are needed for normal bone formation by osteoblasts. (labome.org)
  • Thus, loss of PODXL in early osteoclast lineage cells reduces bone resorption while preserving osteoblast recruitment and bone formation. (labome.org)
  • However, a relatively low level of PODXL expression is required for osteoclast actin ring formation and bone resorption. (labome.org)
  • We will identify structural domains of PODXL and NHERF1 involved in complex formation, membrane expression, differentiation, and internalization during differentiation, resolve the mechanism of down regulation of PODXL, CXCR4, and NHERF1 gene expression by M-CSF, and ascertain the influences of PODXL and binding partners on integrin interactions, actin ring formation, and osteoclast function. (labome.org)
  • Moreover, differentiated osteoclasts proved to be functionally active by pit formation assay. (urotoday.com)
  • Using live imaging, we observed an efficient, dose-dependent inhibition of osteoclast activity, which resulted in the maintenance of bone integrity despite an excess of osteoclast formation. (biologists.org)
  • Interactions between osteoclasts and osteoblasts occur during all phases of bone formation and remodeling and are crucial for bone homeostasis (reviewed by Charles and Aliprantis, 2014 ). (biologists.org)
  • This is a novel report on the role of S100A7 in EGF-induced signaling in breast cancer cells and in osteoclast formation. (harvard.edu)
  • Objective Under both physiological and pathological conditions, bone volume is determined by the rate of bone formation by osteoblasts and bone resorption by osteoclasts. (bmj.com)
  • Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate. (mayo.edu)
  • Therefore, in this study we assessed the role of Y1R deficiency in osteoclast formation and resorption activity. (garvan.org.au)
  • In contrast, exosomes derived from murine fibroblastic cells did not affect osteoclast formation. (diva-portal.org)
  • We reported that interleukin (IL) 6 alone cannot induce osteoclast formation in cocultures of mouse bone marrow and osteoblastic cells, but soluble IL-6 receptor (IL-6R) strikingly triggered osteoclast formation induced by IL-6. (rupress.org)
  • In this study, we examined the mechanism of osteoclast formation by IL-6 and related cytokines through the interaction between osteoblastic cells and osteoclast progenitors. (rupress.org)
  • When dexamethasone was added to the cocultures, IL-6 could stimulate osteoclast formation without the help of soluble IL-6R. (rupress.org)
  • Formation of active phosphorylated c-Src, which was highly present in osteoclast-like cells in cocultures and in peripheral blood mononuclear cell monocultures, was significantly reduced by AZD0530. (aacrjournals.org)
  • Furthermore, it reversibly prevented osteoclast precursor migration from the osteoblast layer to the bone surface and subsequent formation of actin rings and resorption pits. (aacrjournals.org)
  • These data suggest that Src is pivotal for the formation and activity of human osteoclasts, probably through its effect on the distribution of the actin microfilament system. (aacrjournals.org)
  • The reversible effect of AZD0530 on osteoclast formation and activity makes it a promising candidate to temper osteoclastic bone degradation in bone diseases with enhanced osteoclast activity such as osteolytic metastatic bone disease. (aacrjournals.org)
  • Tumor cells in close vicinity to the bone surface are able to contribute to the formation of osteoclasts (multinucleated cells specialized in bone degradation) and thus cause bone lysis, which often results in severe skeletal complications ( 1 ). (aacrjournals.org)
  • CONCLUSION: Mature human osteoclasts present 2 subtypes of EP receptors, namely EP3 and EP4, that mediate different actions of PGE2 on these cells: activation of the EP4 receptors inhibits actin ring formation and activation of the EP3 receptors increases the number of lamellipodia. (jrheum.org)
  • The F-actin (filamentous actin) ring formation was severely defected in C1-depleted osteoclasts but not in a3-depleted and a3 −/− osteoclasts. (biochemj.org)
  • The present study demonstrates that Atp6v1c1 is an essential component of the osteoclast proton pump at the osteoclast ruffled border and that it may regulate F-actin ring formation in osteoclast activation. (biochemj.org)
  • Role of alpha(v)beta(3) integrin in osteoclast migration and formation of the sealing zone. (curehunter.com)
  • In addition, osteoclast-derived LIF (leukemia inhibitory factor) has been shown to reduce sclerostin expression in bone cells and to promote bone formation. (nii.ac.jp)
  • Osteoclasts, which undergo rounds of polarization and depolarization as they progress through the resorptive cycle, possess an unusual and highly dynamic actin cytoskeleton. (nih.gov)
  • To further define some of the actin regulatory proteins involved in osteoclast activity, we previously performed a survey of tropomyosin isoforms in resting and resorbing osteoclasts. (nih.gov)
  • A , Osteoclasts were generated from murine bone marrow cultures and assayed by immunoblot for HMW Tm-2/3 and β-actin as a loading control. (nih.gov)
  • In this study we use immunofluorescence analysis to reveal that PKD2 and PKD3, the isoforms expressed in osteoclasts, are found in the nucleus and cytoplasm, the mitotic spindle and midbody, and in association with the actin belt. (mdpi.com)
  • Treating post-fusion multinucleated osteoclasts with the inhibitors disrupted the osteoclast actin belts and impaired their resorptive activity. (mdpi.com)
  • The actin ring (green) of a bone-resorbing osteoclast. (mayo.edu)
  • These data suggest that maintenance of intracellular pH in osteoclasts through anion exchange regulates the actin superstructures required for bone resorption. (asbmr.org)
  • M-CSF acts through its receptor on the osteoclast, c-fms (colony-stimulating factor 1 receptor), a transmembrane tyrosine kinase -receptor, leading to secondary messenger activation of tyrosine kinase Src. (wikipedia.org)
  • Furthermore, the vitronectin receptor, which has known specificity for osteopontin, is shown preferentially localized at the corresponding area of the osteoclast plasma membrane. (pnas.org)
  • The results thus support the hypothesis that osteoclasts when resorbing bone are anchored by osteopontin bound both to the mineral of bone matrix and to a vitronectin receptor on the osteoclast plasma membrane. (pnas.org)
  • Moreover, we demonstrated a possible role for netrin-1 secreted by osteoclasts during aberrant subchondral bone remodeling in inducing sensory innervation and OA pain through its receptor DCC (deleted in colorectal cancer). (jci.org)
  • We show that the HGF receptor is expressed by human primary osteoclasts, by osteoclast-like cell lines, and by osteoblasts. (uniprot.org)
  • In osteoclasts, HGF receptor activation is followed by increase in intracellular Ca2+ concentration and by activation of the pp60c-Src kinase. (uniprot.org)
  • The androgen receptor has no direct antiresorptive actions in mouse osteoclasts. (sigmaaldrich.com)
  • It has recently been recognized that T cells regulate osteoclasts by secreting a number of cytokines including type I and II IFNs and receptor activator of NF-κB ligand. (jimmunol.org)
  • CD8 + T cells activated by osteoclasts expressed FoxP3, CTLA4, and receptor activator of NF-κB ligand. (jimmunol.org)
  • Recently, osteoclast-associated receptor (OSCAR), an IgG-like receptor, has been identified as an important osteoimmunological mediator. (jimmunol.org)
  • OSCAR expression in bone is highly conserved across different species, and the molecule is an important costimulatory receptor for osteoclast differentiation through activation of NFATc1. (jimmunol.org)
  • Osteoclast precursor cells express cell surface receptors, including the GM-CSF receptor c-fms , receptor activator of NF-κB (RANK), and receptors for costimulatory molecules such as osteoclast-associated receptor (OSCAR) ( 3 ). (jimmunol.org)
  • In particular, we will focus on the expression of P2 receptors by osteoclasts and, more specifically, the P2X(7) receptor and its paradoxical role in osteodast function. (archives-ouvertes.fr)
  • The P2Y(6) receptor stimulates bone resorption by osteoclasts. (semanticscholar.org)
  • Osteoclasts (the bone-resorbing cell) and osteoblasts (the bone-forming cell) display expression of the G protein-coupled P2Y(6) receptor, but the role of this receptor in modulating cell function is unclear. (semanticscholar.org)
  • In this study, we investigated whether an inhibitor of M-CSF receptor (c-Fms) suppresses osteoclast-dependent osteolysis in bone metastatic lesions. (aacrjournals.org)
  • We performed two functional assays (TRAP staining and resorption pit assay) and analysed the expression of osteoclast specific genes. (bmj.com)
  • [9] It was in the beginning of 1980 that the monocyte phagocytic system was recognized as precursor of osteoclasts. (wikipedia.org)
  • The osteoclasts, multinucleared cells originating from the hematopoietic monocyte-macrophage lineage, are responsible for bone resorption. (genome.jp)
  • Multinucleated osteoclasts differentiate from hematopoietic progenitors of the monocyte/macrophage lineage. (mdpi.com)
  • Bone resorbing osteoclasts are terminally differentiated polykaryons of the monocyte/macrophage lineage that are specialized cells responsible for physiological bone resorption as well as pathologic bone loss. (pubmedcentralcanada.ca)
  • Osteoclasts are bone-resorbing cells derived from the monocyte/macrophage lineage. (biologists.org)
  • Osteoclasts are monocyte/macrophage lineage multinucleated cells that play a critical role in bone resorption. (nii.ac.jp)
  • Three theories were dominant: from 1949 to 1970 the connective tissue origin was popular, which stated that osteoclasts and osteoblasts are of the same lineage, and osteoblasts fuse together to form osteoclasts. (wikipedia.org)
  • It may be important to note that while osteoclasts are derived from the hematopoietic lineage, osteoblasts are derived from mesenchymal stem cells. (wikipedia.org)
  • Similar results were observed with the deletion of SLIT3 in LysM-positive cells, including osteoclast lineage cells. (nature.com)
  • Determine the role of osteoclast lineage PODXL expression changes in skeletal acquisition and bone maintenance. (labome.org)
  • 2. Interrogate the molecular mechanisms by which the PODXL, CXCR4, and NHERF-1 complex influences osteoclast lineage cells. (labome.org)
  • This study aimed at deciphering the role of sodium-dependent phosphate transporters during osteoclast differentiation and bone resorption. (nih.gov)
  • Furthermore, the precursor cells that give rise to osteoclasts can also differentiate into other cell types, including dendritic cells. (wiley.com)
  • Ultimately, osteoclast precursor cells migrate to the bone surface and fuse ( 3 , 4 ). (aacrjournals.org)
  • These data strongly suggest the possibility of an autocrine regulation of the osteoclast by HGF and a paracrine regulation of the osteoblast by the HGF produced by the osteoclast. (uniprot.org)
  • Emerging evidence indicates both osteoclasts and osteoblasts play an important role in feedback regulation that affects many systems in the body. (jimmunol.org)
  • The regulation of osteoclasts by T cells has been observed under inflammatory conditions. (jimmunol.org)
  • The regulation of osteoclasts by T cells has also been observed in periodontitis ( 8 ). (jimmunol.org)
  • Leightner AC, Mello Guimaraes Meyers C, Evans MD, Mansky KC, Gopalakrishnan R, Jensen ED. Regulation of Osteoclast Differentiation at Multiple Stages by Protein Kinase D Family Kinases. (mdpi.com)
  • Because of its pivotal role in bone resorption, regulation of osteoclast differentiation is a potential therapeutic approach to the treatment of erosive bone disease. (mdpi.com)
  • Altogether the present data suggest a role for Dlx2 in regulation of skeletal morphogenesis via functions within osteoclasts. (whiterose.ac.uk)
  • These osteoclast precursor RAW264.7 cell clones provide a valuable model for dissecting the cellular and molecular regulation of osteoclast differentiation and activation. (pubmedcentralcanada.ca)
  • Our results clearly show that HA inhibits osteoclast differentiation through TLR4 by interfering with M-CSF signaling, and point that the interaction between ECM components and innate immune receptors can play an important role in the regulation of bone metabolism. (biologists.org)
  • The authors insights into the regulation of apoptosis and activity of the osteoclast will provide valuable information about therapeutic approaches for the treatment of hyper-resorptive skeletal diseases. (eurekaselect.com)
  • Tsuyoshi Miyazaki and Sakae Tanaka, " Regulation of Apoptosis and Activity of the Osteoclast", Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization) (2010) 10: 100. (eurekaselect.com)
  • Very little is known of the regulation of the function of human osteoclasts, largely due to the virtual impossibility of obtaining human osteoclasts ex vivo . (biomedcentral.com)
  • The alpha(v) beta(3) integrin is abundantly expressed in osteoclasts and has been implicated in the regulation of osteoclast function, especially in cell attachment. (curehunter.com)
  • The degradation products are phagocytosed by osteoclasts at the ruffled border. (wikipedia.org)
  • Future research is needed to define the specific role osteoclasts play in the degradation of BAG in vivo. (springer.com)
  • Skeletal growth and homeostasis require the finely orchestrated secretion of mineralized tissue matrices by highly specialized cells, balanced with their degradation by osteoclasts. (whiterose.ac.uk)
  • The osteoclast is the unique bone-resorbing cell that executes its duties by tight attachment to the bone, synthesis and secretion of hydrochloric acid and powerful proteases, internalization of extracellular bone matrix degradation products, and efficient migration along the bone surface. (eurekaselect.com)
  • The idea of osteoclasts being directly involved in OA cartilage degradation is gaining increased attention. (springermedizin.de)
  • but which osteoclast-derived resorption processes that are involved in cartilage degradation have not been investigated. (springermedizin.de)
  • Tumor cells in the bone microenvironment are able to initiate a vicious cycle of bone degradation by mobilizing osteoclasts, multinucleated cells specialized in bone degradation. (aacrjournals.org)
  • These findings suggest that Ki20227 inhibits osteolytic bone destruction through the suppression of M-CSF-induced osteoclast accumulation in vivo . (aacrjournals.org)
  • Taken together, these results suggest that NMP inhibits osteoclast differentiation and attenuates bone resorption. (uzh.ch)
  • Scientifically Proven: Cyanidin In These Fruits Inhibits Osteoclasts, Increases Osteoblasts And Much More! (saveourbones.com)
  • However, in vivo studies have shown that echistatin , an RGD-containing disintegrin which binds to alpha(v)beta(3), inhibits bone resorption without changing the number of osteoclasts on the bone surface, suggesting inhibition of osteoclast activity. (curehunter.com)
  • The objective of this study was to examine how occupancy of alpha(v)beta(3) integrins inhibits osteoclast function, using primary rat osteoclasts and murine pre-fusion osteoclast-like cells formed in a co -culture system. (curehunter.com)
  • Osteoprotegerin (OPG) strongly inhibits osteoclast differentiation. (nii.ac.jp)
  • Conclusions- Long-term alendronate treatment is associated with an increase in the number of osteoclasts, which include distinctive giant, hypernucleated, detached osteoclasts that are undergoing protracted apoptosis. (natap.org)
  • While evidence does indicate that fluoride can inhibit osteoclasts and bone resorption, evidence also indicates that fluoride can increase osteoclast activity and bone resorption. (fluoridealert.org)
  • The activity of osteoclasts is controlled by hormones and cytokines. (wikipedia.org)
  • However, PTH stimulates the osteoblasts to secrete the cytokine called osteoclast-stimulating factor, which is a potent stimulator of the osteoclastic activity. (wikipedia.org)
  • In particular, inhibition of osteoclast activity by alendronate modifies aberrant subchondral bone remodeling and reduces innervation and pain behavior at the early stage of OA. (jci.org)
  • CGRP + sensory nerves in subchondral bone increased along with an increase in osteoclast activity and DRG neuron hypersensitivity during OA progression. (jci.org)
  • Osteoporosis can occur when osteoclast activity outperforms osteoblast activity so more bone is taken up rather than being laid down which can cause weakness and fragility in the bone structures. (spine-health.com)
  • Tartrate-resistant activity was localized histochemically primarily over the osteoclast and appeared as three distinct activity bands when electrophoresed on polyacrylamide gels. (springer.com)
  • The tartrate-sensitive activity was found primarily associated with bone cells other than the osteoclast using histochemical techniques, and was resolved into five bands on polyacrylamide gels. (springer.com)
  • Bovine dentine organic matrix down-regulates osteoclast activity. (biomedsearch.com)
  • Thus, the purpose of this study was to investigate the effect of dentine extracts from bovine deciduous and permanent dentine on osteoclast activity. (biomedsearch.com)
  • The results illustrated that TRAP activity, the resorbed area, and the mRNA levels of osteoclast marker genes seemed to be suppressed by both deciduous and permanent dentine extracts. (biomedsearch.com)
  • These findings indicate that some factors that suppress osteoclast activity are contained in both deciduous and permanent dentine extracts. (biomedsearch.com)
  • Although there was no significant difference in osteoclast activity between deciduous and permanent dentine extracts, osteoclasts incubated with permanent dentine extracts tend to exhibit less resorption activity than those incubated with deciduous dentine extracts. (biomedsearch.com)
  • Molecular contributors to phosphate transport during the resorptive activity of osteoclasts have been controversially discussed. (nih.gov)
  • We will analyze changes in gene and protein expression during osteoclast (trans)differentiation from different precursor cell pools and in various bone sites and relate this to osteoclast activity and sensitivity to therapeutics. (europa.eu)
  • Within the bone/bone marrow microenvironment, T and B lymphocytes as well as mast cells and macrophages provide important signals that affect the coordinated activity of osteoblasts, osteocytes, and osteoclasts through various pathways ( 7 ). (jimmunol.org)
  • Osteoclast differentiation and resorption activity was enhanced in Gnas +/p− cells. (nature.com)
  • Fig. 2 Ror2-mediated signals are required for bone-resorbing activity of osteoclasts. (sciencemag.org)
  • In addition, the distribution and frequency of osteoclasts in the various bones of this frog were examined to relate their occurrence with the state of activity of the parathyroid glands. (rice.edu)
  • A better understanding of pathways that regulate osteoclast differentiation and activity is necessary for the development of new therapies to better manage bone resorption. (mdpi.com)
  • MM is the most frequent cancer to involve bone due to the stimulation of osteoclast (OCL) differentiation and activity. (frontiersin.org)
  • Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals because of an enhanced osteoclast activity, although some contro. (bioportfolio.com)
  • Excess osteoclast activity leads to reduced bone mineral density, a hallmark of diseases such as osteoporosis. (biologists.org)
  • Processes that regulate osteoclast activity are therefore targeted in current osteoporosis therapies. (biologists.org)
  • Strikingly, we also found that bone recovery was efficiently promoted after inhibition of osteoclast activity and that osteoblast distribution was altered, suggesting effects on osteoblast-osteoclast coupling. (biologists.org)
  • In osteoporosis, for example, this leads to increased osteoclast activity and bone resorption, causing reduced bone mineral density and increased fracture risk. (biologists.org)
  • An overview of osteoclast survival and bone-resorbing activity, which are critically regulated by various intracellular signaling pathways, is provided. (eurekaselect.com)
  • Therefore, drugs like AZD0530, designed to inhibit Src activity, could selectively interfere with both tumor and osteoclast activity. (aacrjournals.org)
  • Here we explored the effects of AZD0530 on human osteoclast differentiation and activity. (aacrjournals.org)
  • The effect on osteoclasts formed in vivo was assessed in mouse fetal calvarial explants and in isolated rabbit osteoclasts, where it dose-dependently inhibited osteoclast activity. (aacrjournals.org)
  • Knowledge about proteins specifically involved in the activity of osteoclasts is a prerequisite for developing therapies targeting the osteoclast in pathologies such as cancer-related bone lysis and may also be beneficial in rheumatoid arthritis, osteoporosis, and periodontitis, where excessive and unwanted resorption occurs. (aacrjournals.org)
  • One such protein critical for osteoclast activity is c-Src kinase, which is highly expressed in osteoclasts ( 9 , 10 ). (aacrjournals.org)
  • The body has to regulate osteoclast activity, or else too much bone would be shed. (saveourbones.com)
  • But when the pharmaceutical industry produces synthetic drugs that artificially manipulate osteoclast activity - drugs like the popular bisphosphonate alternative, Prolia - then the trouble starts (more on this later. (saveourbones.com)
  • This shows that bone resorption is regulated not only through modulation of the number of osteoclasts but also by modulation of the resorptive activity of existing osteoclasts. (biomedcentral.com)
  • The results of the present study show for the first time that C1-silencing by lentivirus-mediated RNA interference severely impaired osteoclast acidification activity and bone resorption, whereas cell differentiation did not appear to be affected, which is similar to a3 silencing. (biochemj.org)
  • Osteoclast cells form from a hematopoietic stem cells called monocytes. (bio-medicine.org)
  • During chronic inflammation, these cells migrate to the BM where they survive in an IL-7-dependent manner and where they promote the recruitment of inflammatory monocytes, the main osteoclast progenitors. (bmj.com)
  • Development of animal transplantation models to assess engraftment of human hematopoietic progenitors and in vivo generation of osteoclasts. (labome.org)
  • In vivo, Dlx2 expression in osteoclasts was examined using a Dlx2/LacZ transgenic mouse. (whiterose.ac.uk)
  • In in vivo studies, oral administration of Ki20227 suppressed osteoclast-like cell accumulation and bone resorption induced by metastatic tumor cells in nude rats following intracardiac injection of A375 cells. (aacrjournals.org)
  • The decrease in osteolysis was further associated with diminished osteoclast numbers in vivo . (biomedcentral.com)
  • It is virtually impossible to obtain human osteoclasts ex vivo with which to address this question. (biomedcentral.com)
  • Knockdown of these isoforms via RNA interference results in flattening and increased spreading of osteoclasts, accompanied by diminished motility and altered resorptive capacity. (nih.gov)
  • The osteoclast resorptive apparatus will be studied using in depth and will define the key enzymatic and molecular machinery to be translated into novel site-specific drug targets or biomarkers. (europa.eu)
  • We developed a novel assay for resorptive function of human osteoclasts that minimizes inter-assay variability by using each culture as its own baseline, and that minimizes the confounding effects of agents on differentiation by assessing resorptive function over a short test period. (biomedcentral.com)
  • High molecular weight tropomyosins regulate osteoclast cytoskeletal morphology. (nih.gov)
  • These data suggest that high molecular weight tropomyosins are expressed in fusing osteoclasts to regulate the cytoskeletal scaffolding of these large cells, due at least in part by moderating accessibility of gelsolin to these microfilaments. (nih.gov)
  • This observation suggests that the TREM-2-DAP12 complex may regulate the function of an unexpectedly vast array of myeloid cells, including not only DCs, but also osteoclasts (OCs) and microglial cells, which are critical for bone modeling and brain function, respectively. (rupress.org)
  • Second, these data show that osteoclasts are not only regulated by T cells, but they also can regulate T cells forming a feedback control loop. (jimmunol.org)
  • Interleukin (IL)-6 induction of osteoclast differentiation depends on IL-6 receptors expressed on osteoblastic cells but not on osteoclast progenitors. (rupress.org)
  • Osteoblastic cells expressed a very low level of IL-6R mRNA, whereas fresh mouse spleen and bone marrow cells, both of which are considered to be osteoclast progenitors, constitutively expressed relatively high levels of IL-6R mRNA. (rupress.org)
  • These results clearly indicate that the ability of IL-6 to induce osteoclast differentiation depends on signal transduction mediated by IL-6R expressed on osteoblastic cells but not on osteoclast progenitors. (rupress.org)
  • The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase , a process known as bone resorption . (wikipedia.org)
  • [4] [5] The size of the multinucleated assembled osteoclast allows it to focus the ion transport, protein secretory and vesicular transport capabilities of many macrophages on a localized area of bone. (wikipedia.org)
  • Osteoclast stimulatory transmembrane protein is a protein that in humans is encoded by the OCSTAMP gene. (wikipedia.org)
  • Furthermore, the project focuses on using protein chemistry and proteomic analyses for identification of the unknown factor(s) secreted by the osteoclasts. (nordforsk.org)
  • This evidence suggests that Src may function as an adaptor protein that competes for Pyk2 and relocates it from the peripheral adhesive zone to the central region of osteoclasts in response to osteoprotegerin treatment. (sigmaaldrich.com)
  • The roles of Protein Kinase D (PKD) family of serine/threonine kinases in osteoclasts have not been well characterized. (mdpi.com)
  • Activation of P2X7 receptors causes isoform-specific translocation of protein kinase C in osteoclasts. (semanticscholar.org)
  • RESULTS: Only EP3 and EP4 receptors were detected at the RNA and protein level in osteoclasts. (jrheum.org)
  • The present invention relates to an osteoclast growth inhibitor, an oral composition, and a preventive or therapeutic agent for bone diseases, which inhibit a growth of osteoclasts. (freepatentsonline.com)
  • It's a powerful, anti-inflammatory, antioxidant polyphenol called cyanidin, and research reveals that it has the remarkable ability to inhibit the differentiation of osteoclasts (the cells that tear down bone) while increasing the differentiation of osteoblasts (bone-building cells), and much more. (saveourbones.com)
  • The goal of this work is to determine the roles of kindlin3 and its domains in affecting osteoclast differentiation and function. (osu.edu)
  • When osteoclast-inducing cytokines are used to convert macrophages to osteoclasts, very large cells that may reach 100 µm in diameter occur. (wikipedia.org)
  • Previous studies have shown that serum levels of TNF, IL-6 and IL-17 are increased in AS patients and may be implicated in the development of secondary osteoporosis, since these cytokines are able to induce osteoclast (OC) differentiation and, therefore, bone resorption. (bmj.com)
  • In this study, we uncovered a potent anti-osteoclastogenic effect of hyaluronan (HA), an ECM component present in bone marrow and soft connective tissues, in primary mouse and human osteoclast precursor cell cultures. (biologists.org)
  • Here, we demonstrate that Gsα signaling also regulates osteoclast differentiation during bone modeling and remodeling. (nature.com)
  • Fig. 1 Wnt5a secreted from osteoclasts regulates osteoclast bone-resorbing activities. (sciencemag.org)
  • We show that osteoclasts secrete netrin-1 to induce sensory nerve axonal growth in subchondral bone. (jci.org)
  • Osteoprotegerin may induce podosome reassembly and peripheral adhesive structure detachment by modulating phosphorylation of Pyk2 and Src and their intracellular distribution in osteoclasts. (sigmaaldrich.com)
  • Finally, preosteoclast fuse each other and differentiate into osteoclasts. (hindawi.com)
  • Taken in context, multiple lines of evidence were unable to identify the physiologic function of osteoclast-derived SLIT3, indicating that osteoblasts are the major source of skeletal SLIT3. (nature.com)
  • There has been no evidence of a direct role for Gsα in osteoclast differentiation and function, and the impact of Gsα on skeletal bone quality during modeling and remodeling remains insufficiently understood. (nature.com)
  • The aim of the present study was to establish the expression patterns of Dlx genes in osteoclasts and identify their function in regulating skeletal morphology. (whiterose.ac.uk)
  • DESCRIPTION (provided by applicant): Our long term goal is to delineate the molecular mechanisms by which osteoclasts contribute to bone metabolism with the expectation that this knowledge will guide more effective therapies to promote skeletal health. (labome.org)
  • Osteoclasts are cells specialized for the function of bone catabolism and play, together with osteoblasts, important roles in skeletal development, bone remodeling and fracture healing. (biologists.org)
  • Dr. Westendorf's Skeletal Development and Regeneration Research Laboratory is studying canonical and noncanonical Wnt signaling in osteoblast and osteoclast functions. (mayo.edu)
  • The maintenance of skeletal integrity depends on continual resorption of bone by osteoclasts and its replacement by osteoblasts. (biomedcentral.com)
  • The osteoclasts do not have receptors for parathyroid hormone (PTH). (wikipedia.org)
  • Role of EP3 and EP4 prostaglandin receptors in reorganization of the cytoskeleton in mature human osteoclasts. (jrheum.org)
  • Prostaglandin E2 (PGE2) is well known to influence osteoclasts indirectly, but its direct action on osteoclasts is still controversial and the relevant receptors are unknown. (jrheum.org)
  • Activation or inhibition of these receptors by specific agents could be used to study and influence osteoclast function. (jrheum.org)
  • Osteoclasts become activated in the presence of parathyroid hormone and also in a lymphokine substance produced by lymphocytes in such diseases as multiple myeloma and malignant lymphomas. (thefreedictionary.com)
  • Relation of osteoclast activating factor production to extent of bone disease in multiple myeloma. (biomedsearch.com)
  • Therefore, a challenge for treating multiple myeloma is discovering drugs targeting not only myeloma cells but also osteoclasts and osteoblasts. (aacrjournals.org)
  • We conclude that phosphate transporters of the SLC34 family have no role in osteoclast differentiation and function and propose that Pit-dependent phosphate transport could be pivotal for bone resorption and should be addressed in further studies. (nih.gov)
  • The osteoclasts secrete hydrogen ions, collagenase, cathepsin K and hydrolytic enzymes into this compartment. (wikipedia.org)
  • Our previous study showed that osteoclasts cultured on deciduous dentine exhibited a higher degree of resorption and higher levels of cathepsin K and MMP-9 mRNA than osteoclasts cultured on permanent dentine. (biomedsearch.com)
  • The presence of tumor cell-derived exosomes also clearly decreased the expression of established markers for osteoclast fusion and differentiation, including DC-STAMP, TRAP, cathepsin K, and MMP-9. (diva-portal.org)
  • Osteoprotegerin disrupts peripheral adhesive structures of osteoclasts by modulating Pyk2 and Src activities. (sigmaaldrich.com)
  • Osteoprotegerin has previously been shown to modulate bone mass by blocking osteoclast maturation and function. (sigmaaldrich.com)
  • The detailed mechanisms of osteoprotegerin-induced disassembly of podosomes, disruption of adhesive structures and modulation of adhesion-related proteins in osteoclasts, however, are not well characterized. (sigmaaldrich.com)
  • In this study, tartrate-resistant acidic phosphatase staining demonstrated that osteoprotegerin inhibited differentiation of osteoclasts. (sigmaaldrich.com)
  • The use of scanning electron microscopy, real-time cell monitoring and confocal microscopy indicated that osteoclasts responded in a time and dose-dependent manner to osteoprotegerin treatments with retraction of peripheral adhesive structures and detachment from the extracellular substrate. (sigmaaldrich.com)
  • osteoprotegerin induced increased intracellular labeling of Tyr 402 in Pyk2, Tyr 416 in Src, increased dephosphorylation of Tyr 527 in Src, and increased Pyk2/Src association in the central region of osteoclasts. (sigmaaldrich.com)
  • In the present study, we found that the V-ATPase subunit Atp6v1c1 (C1) is highly expressed in osteoclasts, whereas subunits Atp6v1c2a (C2a) and Atp6v1c2b (C2b) are not. (biochemj.org)
  • This extensively folded or ruffled border facilitates bone removal by dramatically increasing the cell surface for secretion and uptake of the resorption compartment contents and is a morphologic characteristic of an osteoclast that is actively resorbing bone. (wikipedia.org)
  • HGF induces changes in osteoclast shape and stimulates chemotactic migration and DNA replication. (uniprot.org)
  • Furthermore, this approach can be used to study the function of other genes of interest in the osteoclasts, i.e. genes potentially involved in the bone resorption process, and thus detect new targets for pharmacological modulation of the bone remodelling process potentially important for treatment of osteoporosis. (nordforsk.org)
  • Such specific expression patterns have also been reported in osteoclasts for Msx genes. (whiterose.ac.uk)
  • cDNA expression profiling of osteoclast precursor RAW264.7 cell clones demonstrates appropriate expression of a large number of genes before and after osteoclastic differentiation. (pubmedcentralcanada.ca)
  • These transcription factors, and others, direct the expression or repression of the unique set of genes associated with osteoclast differentiation and activation. (pubmedcentralcanada.ca)