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 ...
TY - JOUR. T1 - TGF-β inducible early gene 1 regulates osteoclast differentiation and survival by mediating the NFATc1, AKT, and MEK/ERK signaling pathways. AU - Cicek, Muzaffer. AU - Vrabel, Anne. AU - Sturchio, Catherine. AU - Pederson, Larry. AU - Hawse, John R.. AU - Subramaniam, Malayannan. AU - Spelsberg, Thomas C.. AU - Oursler, Merry Jo. PY - 2011. Y1 - 2011. N2 - TGF-β Inducible Early Gene-1 (TIEG1) is a Krüppel-like transcription factor (KLF10) that was originally cloned from human osteoblasts as an early response gene to TGF-β treatment. As reported previously, TIEG1-/- mice have decreased cortical bone thickness and vertebral bone volume and have increased spacing between the trabeculae in the femoral head relative to wildtype controls. Here, we have investigated the role of TIEG1 in osteoclasts to further determine their potential role in mediating this phenotype. We have found that TIEG1-/- osteoclast precursors differentiated more slowly compared to wildtype precursors in ...
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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 ...
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 ...
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.. ...
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 - ...
Chappard D, Alexandre C, Riffat G (1983). "Histochemical identification of osteoclasts. Review of current methods and ...
Bone resorption is carried out by specialized bone cells known as osteoclasts. A surge in osteoclast activity can lead to ... Teitelbaum, Steven L. (Sep 2000). "Bone Resorption by Osteoclasts". Science. 289 (5484): 1504-1508. Bibcode:2000Sci...289.1504T ...
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): ...
Attachment of the osteoclast to the osteon begins the process. The osteoclast then induces an infolding of its cell membrane ... Calcitonin decreases osteoclast activity, and decreases the formation of new osteoclasts, resulting in decreased resorption. ... The osteoclasts are multi-nucleated cells that contain numerous mitochondria and lysosomes. These are the cells responsible for ... Osteoclasts are prominent in the tissue destruction found in psoriatic arthritis and rheumatological disorders. The human body ...
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 ...
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 ...
... is constantly remodeled by the resorption of osteoclasts and created by osteoblasts. Osteoclasts are large cells with ... and can bind to receptors on osteoclasts to directly inhibit osteoclast activity. Osteoprotegerin is secreted by osteoblasts ... Osteoclasts are very large multinucleate cells that are responsible for the breakdown of bones by the process of bone ... Because the osteoclasts are derived from a monocyte stem-cell lineage, they are equipped with phagocytic-like mechanisms ...
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- ...
... lowers blood calcium and phosphorus mainly through its inhibition of osteoclasts. Osteoblasts do not have calcitonin ... Inhibits osteoclast activity in bones, which break down the bone Minor effect: Inhibits renal tubular cell reabsorption of Ca2+ ... The calcitonin receptor is a G protein-coupled receptor localized to osteoclasts as well kidney and brain cells. It is coupled ... "Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and autoradiographic characterization". J. Clin. Invest ...
It is postulated that osteoclasts are the cells responsible for the resorption of the root surface. Osteoclasts can break down ... 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 ... The pulp must be vital below the area of resorption to provide osteoclasts with nutrients. If the pulp becomes totally necrosed ...
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 ... In osteoclasts, TRAP is localized within the ruffled border area, the lysosomes, the Golgi cisternae and vesicles. Mammalian ... Modulation of osteoclast adhesion in vitro". The Journal of Biological Chemistry. 269 (21): 14853-14856. doi:10.1016/S0021-9258 ...
Specifically, OPN anchors osteoclasts to the surface of bones where it is immobilized by its mineral-binding properties ... OPN serves to initiate the process by which osteoclasts develop their ruffled borders to begin bone resorption. OPN contains ... Merry K, Dodds R, Littlewood A, Gowen M (April 1993). "Expression of osteopontin mRNA by osteoclasts and osteoblasts in ... OPN expression in bone predominantly occurs by osteoblasts and osteocyctes (bone-forming cells) as well as osteoclasts (bone- ...
NOTCH2 is also shown to regulate RANK-L osteoclastogenesis, which is the production of functional osteoclasts. Osteoclasts are ...
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 ... Collagen fibers of woven bone Osteoclast displaying many nuclei within its "foamy" cytoplasm. Light micrograph of decalcified ...
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 ...
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 activity is stopped and osteoblasts take over, utilising the excess calcium in the bloodstream to form new bone. ... In the bones, the presence of PTH stimulates osteoclasts. These cells break down bone to release calcium into the bloodstream ...
"Inhibitors of Osteoclast Differentiation fromCephalotaxus koreana". Journal of Natural Products. 70 (12): 2029-32. doi:10.1021/ ...
Alendronate inhibits osteoclast-mediated bone-resorption. Like all bisphosphonates, it is chemically related to inorganic ... Further, studies suggest that users of alendronate have an increase in the numbers of osteoclasts and develop giant, more ... Weinstein RS, Roberson PK, Manolagas SC (January 2009). "Giant osteoclast formation and long-term oral bisphosphonate therapy ... multinucleated osteoclasts; the significance of this development is unclear. Fosamax has been linked to a rare type of leg ...
Osteoclast-associated immunoglobulin-like receptor is a protein that in humans is encoded by the OSCAR gene. Osteoclasts are ... "Entrez Gene: OSCAR osteoclast-associated receptor". Pupello DF, Lipton M, Shumway NE (1976). "An unusual case of a bullet ... Kim N, Takami M, Rho J, Josien R, Choi Y (Jan 2002). "A novel member of the leukocyte receptor complex regulates osteoclast ... This gene encodes an osteoclast-associated receptor (OSCAR), which is a member of the leukocyte receptor complex (LRC) protein ...
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 ...
Human osteoclasts and osteoclast-like cells synthesize and release high basal and inflammatory stimulated levels of the potent ... we report here for the first time that human bone marrow-derived osteoclast-like cells (hOCL) as well as authentic bone- ... resorbing human osteoclasts (hOC) isolated from osteoporotic femoral heads express messenger RNA (mRNA) for IL-8 and secrete ...
IL-1b produced in response to treatment with both MSU and RANKL is involved in osteoclast differentiation in part through the ... RAW 264.7 murine macrophage cells were incubated with MSU crystals or RANKL and differentiated into osteoclast-like cells as ... MSU crystals in the presence of RANKL augmented osteoclast differentiation, with enhanced mRNA expression of NFATc1, cathepsin ... Treatment with both MSU crystals and RANKL induced osteoclast differentiation by activating downstream molecules in the RANKL- ...
Medaka Osteoclast g b v y [ W , u ڂ v ł̎ y [ W ...
Osteoclast function was tested in isolated avian osteoclasts and was measured in terms of tartrate-resistant acid phosphatase ( ... Osteoclast function was tested in isolated avian osteoclasts and was measured in terms of tartrate-resistant acid phosphatase ( ... This cessation of osteoclast activity may be an essential preliminary step to the new bone formation that occurs at resorption ... This cessation of osteoclast activity may be an essential preliminary step to the new bone formation that occurs at resorption ...
Osteoclasts are multinucleated cells formed by fusion of mononuclear precursors in response to receptor activator of nuclear ... N2 - Osteoclasts are multinucleated cells formed by fusion of mononuclear precursors in response to receptor activator of ... AB - Osteoclasts are multinucleated cells formed by fusion of mononuclear precursors in response to receptor activator of ... abstract = "Osteoclasts are multinucleated cells formed by fusion of mononuclear precursors in response to receptor activator ...
TSC1 regulates osteoclast podosome organization and bone resorption through mTORC1 and Rac1/Cdc42. In: Cell Death and ... TSC1 regulates osteoclast podosome organization and bone resorption through mTORC1 and Rac1/Cdc42. / Xu, Song; Zhang, Yue; Wang ... TSC1 regulates osteoclast podosome organization and bone resorption through mTORC1 and Rac1/Cdc42. Cell Death and ... N2 - Reorganization of the podosome into the sealing zone is crucial for osteoclasts (OCLs) to resorb bone, but the underlying ...
LCA is evident on the surface of fetal human osteoclasts in bone imprints and cryostat sections. LCA was also found on ... The intensity and pattern of osteoclast reactivity were similar to those of foreign-body type macrophage polykaryons in ... These results favour derivation of osteoclasts and their precursors from the multipotential haemopoietic stem cell which ... the presence of LCA on osteoclasts in both fetal and adult human bone specimens has been determined by immunohistochemistry. ...
... Li Duan1,2. , Paul de Vos3. , Marijke Faas3. , ... IkappaBalpha regulates Hes1 in osteoclast differentiation and resorption. Front. Biosci. (Elite Ed) 2010, 2(3), 1065-1072. ... During osteoclast differentiation and resorption, both NF-kappaB and Notch signalling are activated. This study defines the ... The number of cells that differentiated into osteoclasts was quantified. The resorption area was measured. NF-kappaB ...
Modeling the interactions between osteoblast and osteoclast activities in bone remodeling * Modeling the interactions between ... Modeling the interactions between osteoblast and osteoclast activities in bone remodeling * Modeling the interactions between ... Modeling the interactions between osteoblast and osteoclast activities in bone remodeling * Modeling the interactions between ... Modeling the interactions between osteoblast and osteoclast activities in bone remodeling * Modeling the interactions between ...
Durdan, M. M., Azaria, R. D., & Weivoda, M. M. (2022). Novel insights into the coupling of osteoclasts and resorption to bone ... Durdan, MM, Azaria, RD & Weivoda, MM 2022, Novel insights into the coupling of osteoclasts and resorption to bone formation, ... Durdan, Margaret M. ; Azaria, Ruth D. ; Weivoda, Megan M. / Novel insights into the coupling of osteoclasts and resorption to ... Novel insights into the coupling of osteoclasts and resorption to bone formation. / Durdan, Margaret M.; Azaria, Ruth D.; ...
To investigate how osteoclasts develop around implanted OCP, we examined osteoclast differentiation using OCP crystals in vitro ... To investigate how osteoclasts develop around implanted OCP, we examined osteoclast differentiation using OCP crystals in vitro ... To investigate how osteoclasts develop around implanted OCP, we examined osteoclast differentiation using OCP crystals in vitro ... To investigate how osteoclasts develop around implanted OCP, we examined osteoclast differentiation using OCP crystals in vitro ...
HomePosts tagged "Osteoclasts". Obesity Increases Risk of Gum Disease, Destruction of Jaw Bone Tissues. Articles November 17, ...
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Anaplastic thyroid carcinoma with osteoclast-like giant cells.. Authors: Valand, A G. Ramraje, Sushma N. Pandeya, B S. Shedge, ... Valand AG, Ramraje SN, Pandeya BS, Shedge R, Aware S. Anaplastic thyroid carcinoma with osteoclast-like giant cells. Journal of ... A case of anaplastic thyroid carcinoma with osteoclast-like giant cells is reported. This is an unusual malignant thyroid ... Pleomorphic cells and tumour giant cells were accompanied by numerous osteoclast-like multinucleated giant cells. ...
Osteoclasts were differentiated in vitro from CD14 selected monocytes in RANKL and CSF-1, and characterized by cathepsin K ... NO inhibits or kills osteoclasts, but the mechanism of action of NO in human bone turnover is not clear. To address this, we ... We conclude that NO is produced by human osteoclasts and regulates acid secretion and cellular motility, in keeping with ... Cell attachment was labeled with monoclonal antibody 23C6, specific for a binding domain of a key osteoclast attachment protein ...
The osteoclasts now come in and remodel the bone, reshaping it to its proper form. They break down and digest excess bone in a ... This balance between building bone and breaking it down is called bone homeostasis: Osteoblasts and osteoclasts are equally ... There is a better way! Incorporate the osteoclast technique into your presentation! ...
Modeling role of ER in transcellular calcium flux in bone resorbing osteoclasts. Lookup NU author(s): Dr Harish Datta ...
The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and ... Osteopontin is a non-collagenous bone matrix glycoprotein secreted by osteoclasts and is implicated both in osteoclast ... Osteoclast precursors expressing BTK and CXCR4 migrate towards SDF-1α and, in turn, SDF-1α induces BTK activation in MM cells58 ... The mature osteoclasts attach to the bone surface in order to become activated and the bone resorption process is initiated18. ...
Osteoclasts are multinuclear cells of myeloid lineage responsible for bone resorption. The anti-inflammatory property of ... CAPE (From Propolis) Inhibits Osteoclasts. Abstract. Caffeic acid phenethyl ester inhibits osteoclastogenesis by suppressing NF ... Finally, CAPE significantly inhibited the RANKL-induced osteoclast formation in mouse calvariae in vivo. We propose that CAPE ... Since the regulatory mechanism of differentiation and activation of osteoclasts shares many well-known signaling pathways with ...
Furthermore, pepstatin A also suppressed differentiation from pre-osteoclast cells to mononuclear osteoclast cells dose- ... Furthermore, pepstatin A also suppressed differentiation from pre-osteoclast cells to mononuclear osteoclast cells dose- ... Furthermore, pepstatin A also suppressed differentiation from pre-osteoclast cells to mononuclear osteoclast cells dose- ... Furthermore, pepstatin A also suppressed differentiation from pre-osteoclast cells to mononuclear osteoclast cells dose- ...
PTH activates osteoclasts. Osteoclast activation results in bone resorption and a release of ionized calcium into the ECF. ... The effect of PTH on osteoclasts seems more important than the effect on osteoblasts. ...
Light, a TNF-superfamily member, induces osteoclast formation in vitro; A novel mediator of bone resorption? ... Light, a TNF-superfamily member, induces osteoclast formation in vitro; A novel mediator of bone resorption? ...
Further, osteoclast precursor cells from the transgenic mice show defects in expression and nuclear localization of NFATc1. ... Further, osteoclast precursor cells from the transgenic mice show defects in expression and nuclear localization of NFATc1. ... Further, osteoclast precursor cells from the transgenic mice show defects in expression and nuclear localization of NFATc1. ... Further, osteoclast precursor cells from the transgenic mice show defects in expression and nuclear localization of NFATc1. ...
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Recently the osteoclast differentiation factor (ODF), better termed RANKL (receptor activator of NF-kappaB ligand), expressed ... MCF-7, MDA-MB-231, and T47D cells did not act as surrogate osteoblasts to support osteoclast formation in coculture experiments ... osteoclast formation resulted without the addition of any osteotropic agents; cocultures with MCF-7 or MCF-7 cells transfected ... which were associated with increased osteoclast formation, elevated plasma PTHrP concentrations and hypercalcaemia compared ...
Regulation of Osteoclast Activity. Shortcut Guy Regulation This fourth film in our bone biology series focuses on the link ... osteoclasts, osteoprotegerin, parathyroid hormone, precursor cells, PTH, rank, rank ligand, rankl, research, resorption, ...
Since osteoclasts play an active role in primary bone tumors and bone metastases, the use of anti-osteoclastic agents ... Since osteoclasts play an active role in primary bone tumors and bone metastases, the use of anti-osteoclastic agents ... Osteoclasts also accompany undifferentiated carcinomas of many organs, especially pancreas, thyroid, bladder and ovary. ... Osteoclasts also accompany undifferentiated carcinomas of many organs, especially pancreas, thyroid, bladder and ovary. ...
Osteopetrosis is a clinical syndrome characterized by the failure of osteoclasts to resorb bone. As a consequence, bone ... Bone resorption by osteoclasts. Science. 2000 Sep 1. 289(5484):1504-8. [QxMD MEDLINE Link]. ...
Rat OSCAR (Osteoclast Associated Receptor) ELISA Kit. E-EL-R0698 Regular price $580.00. $499.00 You Pay ...
  • Bone remodeling consists of resorption by osteoclasts (OCs) and formation by osteoblasts (OBs). (elsevier.com)
  • Coculturing of mouse bone marrow cells and osteoblasts in OCP-coated cell culture plates induced osteoclast differentiation, whereas that did not occur without coating. (elsevier.com)
  • In the presence of OCP, osteoblasts expressed receptor activator of NF-κB ligand (RANKL), an osteoclast differentiation factor. (elsevier.com)
  • These results suggest that OCP itself decreases calcium levels around implanted OCP, which induces osteoclast differentiation through RANKL expression by osteoblasts. (elsevier.com)
  • Osteoblasts and osteoclasts are equally important in the process of maintaining healthy bone, not just when bones are broken, but throughout our lives. (speakschmeak.com)
  • The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and suppression of osteoblasts, resulting in bone loss. (nature.com)
  • Bone remodeling takes place in the basic multicellular unit (BMU), which consists of osteoblasts, osteoclasts, and osteocytes within the bone-remodeling cavity. (nature.com)
  • Although the role of GSK-3β in osteoblasts is well characterized as a negative regulator of β-catenin, its effect on osteoclast formation remains largely unidentified. (elsevier.com)
  • Breast cancer cells interact with osteoblasts to support osteoclast formation. (ox.ac.uk)
  • Recently the osteoclast differentiation factor (ODF), better termed RANKL (receptor activator of NF-kappaB ligand), expressed by osteoblasts has been cloned as well as its cognate signaling receptor, receptor activator of NFkappaB (RANK), and a secreted decoy receptor osteoprotegerin (OPG) that limits RANKL's biological action. (ox.ac.uk)
  • MCF-7, MDA-MB-231, and T47D cells did not act as surrogate osteoblasts to support osteoclast formation in coculture experiments, a result consistent with the fact that they do not express RANKL. (ox.ac.uk)
  • Osteoclast is a specialized cell that originates from monocytic lineage, communicates closely with osteoblasts under physiological conditions, participates in bone modeling and re-modeling, contributes to calcium homeostasis and osteoimmunity. (por-journal.com)
  • Vitamin D3, zinc, and boron all help, but new studies have shown that certain plant compounds can selectively inhibit osteoclasts and stimulate osteoblasts, thus making bone much stronger. (newsmax.com)
  • One of the best of these compounds is baicalein, which inhibits osteoclasts and stimulates osteoblasts in a significant way. (newsmax.com)
  • The administration of the low doses of C. asiatica extract affects the number of osteocytes and osteoclasts but not osteoblasts in ovariectomized rats. (innovareacademics.in)
  • Estrogen protects bone by inducing fas ligand in osteoblasts to regulate osteoclast survival. (innovareacademics.in)
  • Old bone is drawn upon to supply instant demands for calcium (osteoclasts) and is replaced by new bone material (osteoblasts) to keep the skeleton strong. (healthandwellnesstimes.com)
  • while osteoblasts/cytes have alk phosphatase to aid in mineralization, osteoclasts have acid phosphatase. (orthonet.on.ca)
  • With time, the Bonefill is partially remodeled through the action of osteoclasts and osteoblasts, being a viable alternative to autologous bone in defects suitable for its use and indication. (dentrealstore.com)
  • This study revealed that MSU crystals contribute to enhanced osteoclast formation through activation of RANKL-mediated pathways and recruitment of IL-1b. (hindawi.com)
  • Although macrophages, neutrophils, and endothelial cells are considered the primary sources of inflammation-induced IL-8 increases, we report here for the first time that human bone marrow-derived osteoclast-like cells (hOCL) as well as authentic bone-resorbing human osteoclasts (hOC) isolated from osteoporotic femoral heads express messenger RNA (mRNA) for IL-8 and secrete high levels of IL-8 during culture. (nih.gov)
  • LCA is evident on the surface of fetal human osteoclasts in bone imprints and cryostat sections. (ox.ac.uk)
  • Autocrine and paracrine nitric oxide regulate attachment of human osteoclasts. (ox.ac.uk)
  • To address this, we studied effects of NO on attachment and motility of human osteoclasts on mineralized and tissue culture substrates under defined conditions. (ox.ac.uk)
  • We conclude that NO is produced by human osteoclasts and regulates acid secretion and cellular motility, in keeping with autocrine and paracrine NO regulation of the resorption cycle. (ox.ac.uk)
  • Bone resorption activity of fully differentiated human osteoclasts and of osteoclast-like cell lines, from giant cell tumors of bone (GCT), was highly increased by the presence of MDA-231 CM. Moreover, while MDA-231 by themselves did not produce IL-6 tumor cell, CM increased the secretion of IL-6 by primary human osteoclasts and GCT cell lines compared to untreated controls. (unifg.it)
  • Together, these results indicate that DS regulates osteoclast formation through binding to RANKL and inhibition of signal transduction in osteoclast progenitor cells, suggesting that it has an important role in bone metabolism in pathological conditions. (elsevier.com)
  • This study shows how skullcapflavone II (SFII), a flavonoid with anti-inflammatory activity, regulates osteoclast differentiation, survival, and function. (ewha.ac.kr)
  • The aim of this study was to clarify the role of monosodium urate (MSU) crystals in receptor activator of nuclear factor kB ligand- (RANKL-) RANK-induced osteoclast formation. (hindawi.com)
  • Receptor activator of nuclear factor- B ligand (RANKL) and its receptor RANK are components in a signaling pathway that is essential for osteoclast differentiation, activation, and survival [ 1 - 3 ]. (hindawi.com)
  • Osteoclasts are multinucleated cells formed by fusion of mononuclear precursors in response to receptor activator of nuclear factor κB (NF-κB) ligand (RANKL). (monash.edu)
  • CAPE potently suppressed osteoclastogenesis in cultures of bone marrow-derived precursor cells with the osteoclast differentiation factor , receptor activator of nuclear factor kappaB ligand (RANKL). (osteoporosis-studies.com)
  • In this study, we found that pepstatin A suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation. (elsevier.com)
  • Here, we show that the GSK-3β inactivation upon receptor activator of NF-κB ligand (RANKL) stimulation is crucial for osteoclast differentiation. (elsevier.com)
  • Osteoclast formation was also assessed in control CD14 cultures stimulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANK-L). Although Activin-A increased activation of the pSMAD3 pathway in both control and FOP PLF, it increased ACVR1, FK binding protein 12 (FKBP12), an inhibitor of DNA binding 1 protein (ID-1) expression only in FOP PLF. (vumc.nl)
  • Prolia works by blocking a protein called RANK (receptor activator of nuclear factor kappa beta) and helps prevent bone cells called osteoclasts from breaking down bone in the body. (medlineplus.gov)
  • Treatment with both MSU crystals and RANKL induced osteoclast differentiation by activating downstream molecules in the RANKL-RANK pathway including tumor necrosis factor receptor-associated factor 6 (TRAF-6), JNK, c-Jun, and NFATc1. (hindawi.com)
  • Osteoclasts are considered crucial effector cells that are mainly responsible for bone resorption in bone homeostasis [ 1 - 3 ]. (hindawi.com)
  • Osteoclast function was tested in isolated avian osteoclasts and was measured in terms of tartrate-resistant acid phosphatase (TRAP) activity, oxygen-derived free radical production, and formation of characteristic resorption lacunae on slices of sperm whale dentine. (soton.ac.uk)
  • TGF beta had no effect on the resorption capacity of isolated osteoclasts in concentrations that inhibited TRAP activity and nitroblue tetrazolium staining. (soton.ac.uk)
  • This cessation of osteoclast activity may be an essential preliminary step to the new bone formation that occurs at resorption sites during bone remodeling. (soton.ac.uk)
  • During osteoclast differentiation and resorption, both NF-kappaB and Notch signalling are activated. (imrpress.com)
  • NF-kappaB inactivation inhibited the differentiation and resorption ability of osteoclasts. (imrpress.com)
  • In conclusion, our data suggest IkappaBalpha regulates Hes1-mediated activity in osteoclast differentiation and resorption, which support a cross-talk between NF-kappaB and Notch in osteoclast activity. (imrpress.com)
  • Durdan, MM, Azaria, RD & Weivoda, MM 2022, ' Novel insights into the coupling of osteoclasts and resorption to bone formation ', Seminars in Cell and Developmental Biology , vol. 123, pp. 4-13. (elsevier.com)
  • Osteoclasts were differentiated in vitro from CD14 selected monocytes in RANKL and CSF-1, and characterized by cathepsin K expression, tartrate-resistant acid phosphatase (TRAP) activity, acid secretion, and lacunar resorption. (ox.ac.uk)
  • Osteoclasts are multinuclear cells of myeloid lineage responsible for bone resorption. (osteoporosis-studies.com)
  • Breast cancers commonly cause osteolytic metastases in bone, a process that is dependent upon osteoclast-mediated bone resorption. (ox.ac.uk)
  • Bone resorption by osteoclasts. (medscape.com)
  • Breast cancers commonly cause osteolytic metastases in bone, a process that is dependent upon osteoclast-mediated bone resorption, but the mechanism responsible for tumor-mediated osteoclast activation has not yet been clarified. (unifg.it)
  • In the present study we utilized a well-known human breast cancer cell line (MDA-231) in order to assess its capability to influence osteoclastogenesis in human bone marrow cultures and bone resorption in fully differentiated osteoclasts. (unifg.it)
  • These data suggest that MDA-231 produce osteoclastic activating factor(s) that increase both osteoclast formation in bone marrow culture and bone resorption activity by mature cells. (unifg.it)
  • This study investigated the effects of polyunsaturated fatty acids on osteoclast formation and bone resorption in RAW 264.7 murine pre-osteoclasts. (satnt.ac.za)
  • The RANKL-RANK bond stimulates the maturation of preosteoclasts into osteoclasts, resulting in alveolar bone resorption. (ejmcm.com)
  • Effect of cytokines on osteoclast formation and bone resorption during mechanical force loading of the periodontal membrane. (bvsalud.org)
  • These results suggest that osteoclast formation and bone resorption caused by loading forces on the periodontal ligament depend on TNF-α. (bvsalud.org)
  • In this review we describe and discuss the effect of cytokines in the periodontal ligament on osteoclast formation and bone resorption during mechanical force loading. (bvsalud.org)
  • Curcumin is especially effective for inhibiting osteoclasts, and thus inhibiting bone resorption. (newsmax.com)
  • In addition, SFII attenuated survival, migration, and bone resorption, with a decrease in the expression of integrin b 3 , Src, and p130 Crk‐associated substrate, and the activation of RhoA and Rac1 in differentiated osteoclasts. (ewha.ac.kr)
  • These findings suggest that SFII inhibits osteoclastogenesis through redox regulation of MAPKs, Src, and CREB and attenuates the survival and resorption function by modulating the integrin pathway in osteoclasts. (ewha.ac.kr)
  • FOSAMAX * (alendronate sodium) is a bisphosphonate that acts as a specific inhibitor of osteoclast-mediated bone resorption. (rxdrugnews.com)
  • At the cellular level, alendronate shows preferential localization to sites of bone resorption, specifically under osteoclasts. (rxdrugnews.com)
  • The osteoclasts adhere normally to the bone surface but lack the ruffled border that is indicative of active resorption. (rxdrugnews.com)
  • Thus, alendronate must be continuously administered to suppress osteoclasts on newly formed resorption surfaces. (rxdrugnews.com)
  • Denosumab is a human monoclonal antibody (IgG2) whose mechanism of action inhibits osteoclast formation, function and survival, causing a decrease in bone resorption. (bvsalud.org)
  • RAW 264.7 murine macrophage cells were incubated with MSU crystals or RANKL and differentiated into osteoclast-like cells as confirmed by staining for tartrate-resistant acid phosphatase (TRAP) and actin ring, pit formation assay, and TRAP activity assay. (hindawi.com)
  • MSU crystals in the presence of RANKL augmented osteoclast differentiation, with enhanced mRNA expression of NFATc1, cathepsin K, carbonic anhydrase II, and matrix metalloproteinase-9 (MMP-9), in comparison to RAW 264.7 macrophages incubated in the presence of RANKL alone. (hindawi.com)
  • IL-1b produced in response to treatment with both MSU and RANKL is involved in osteoclast differentiation in part through the induction of TRAF-6 downstream of the IL-1b pathway. (hindawi.com)
  • It has not been clearly determined for molecular mechanism of MSU crystals on osteoclast formation in the downstream of RANKL-RANK pathway. (hindawi.com)
  • In this study, we investigated whether MSU crystals in the presence of RANKL promote differentiation of murine RAW 264.7 macrophages into osteoclasts. (hindawi.com)
  • We also sought to identify the role of cytoplasmic protein kinases and transcription factors downstream of the RANKL-RANK signaling pathway and of IL-1 in osteoclast formation. (hindawi.com)
  • Finally, CAPE significantly inhibited the RANKL-induced osteoclast formation in mouse calvariae in vivo. (osteoporosis-studies.com)
  • Regulation of GSK-3β activity in bone marrow macrophages by retroviral expression of the constitutively active GSK-3β (GSK3β-S9A) mutant inhibits RANKL-induced osteoclastogenesis, whereas expression of the catalytically inactive GSK-3β (GSK3β-K85R) or small interfering RNA (siRNA)-mediated GSK-3β silencing enhances osteoclast formation. (elsevier.com)
  • In addition, immunoblot analyses revealed that DS reduced the levels of phosphorylation of p38 mitogen-activated protein kinase and extracellular signal-regulated kinase protein in mouse osteoclast progenitor cells stimulated with RANKL. (elsevier.com)
  • Suppressing Tbx3 in osteoclast precursors reduced JDP2 expression and significantly impaired RANKL/CSF1-induced osteoclastogenesis. (divbiolchem.org)
  • Further, osteoclast precursor cells from the transgenic mice show defects in expression and nuclear localization of NFATc1. (elsevier.com)
  • PLF-induced osteoclast formation and gene expression were studied by coculturing control and FOP PLF with CD14-positive osteoclast precursor cells from healthy donors. (vumc.nl)
  • Since the regulatory mechanism of differentiation and activation of osteoclasts shares many well-known signaling pathways with that of inflammation, we investigated whether CAPE has any effect on osteoclastogenesis. (osteoporosis-studies.com)
  • This process relies heavily on the regulation of osteoblast and osteoclast function, which itself is regulated by prostaglandins. (thetraumapro.com)
  • Osteoclast differentiation and activation. (bvsalud.org)
  • Estrogen prevents bone loss via estrogen receptor alpha and induction of fas ligand in osteoclasts. (innovareacademics.in)
  • Pepstatin A suppressed the formation of multinuclear osteoclasts dose-dependently. (elsevier.com)
  • This inhibition of the formation only affected osteoclast cells, i.e., not osteoblast-like cells. (elsevier.com)
  • This inhibition seems to be independent of the activities of proteinases such as cathepsin D, because the formation of osteoclasts was not suppressed with the concentration that inhibited the activity of cathepsin D. Cell signaling analysis indicated that the phosphorylation of ERK was inhibited in pepstatin A-treated cells, while the phosphorylation of IκB and Akt showed almost no change. (elsevier.com)
  • Pharmacological inhibition of GSK-3β further confirmed the negative role of GSK-3β in osteoclast formation. (elsevier.com)
  • cocultures with MCF-7 or MCF-7 cells transfected with pcDNAIneo required exogenous agents for osteoclast formation. (ox.ac.uk)
  • Using a murine model of breast cancer metastasis to bone, we established that MCF-7 cells that overexpress PTHrP caused significantly more bone metastases, which were associated with increased osteoclast formation, elevated plasma PTHrP concentrations and hypercalcaemia compared with parental or empty vector controls. (ox.ac.uk)
  • Mature and immature myeloid cells, including osteoclasts, play an active role in the tumor progression in primary and metastatic tumor microenvironment, in epithelial-mesenchymal transition (EMT), mesenchymal-epithelial-transition (MET), and cancer stem cell formation. (por-journal.com)
  • Whether Activin-A also affects osteoclast formation in FOP is not known. (vumc.nl)
  • Activin-A inhibited PLF mediated osteoclast formation albeit only significantly when induced by FOP PLF. (vumc.nl)
  • Activin-A also inhibited osteoclast formation in M-CSF and RANK-L mediated monocultures of CD14+ cells by inhibiting their proliferation. (vumc.nl)
  • in addition to the known Activin-A-mediated HO, this study shows that Activin-A may also inhibit osteoclast formation, thereby further promoting HO formation. (vumc.nl)
  • The present study examined the effect of sodium salicylate on the formation of osteoclast-like cells in vitro. (ui.ac.id)
  • Central to the pathogenesis of osteoporosis is the ability of estrogen deficiency to increase osteoclast formation by enhancing stromal cell production of the osteoclastogenic cytokine macrophage colony-stimulating factor (M-CSF). (wustl.edu)
  • Estrogen replacement fails to block M-CSF mRNA expression and osteoclast formation in ovariectomized mice lacking Egr- 1, confirming the critical role played by this transcription factor in mediating the antiosteoclastogenic effects of estrogen. (wustl.edu)
  • Thus, by downregulating formation of a novel Egr-1/Sp-1 complex in stromal cells, estrogen deficiency results in enhanced levels of free Sp-1 and increased M- CSF gene expression and osteoclast formation. (wustl.edu)
  • Studies have found that inflammatory cytokines such as IL-12 and IFN-γ strongly inhibit osteoclast formation and tooth movement . (bvsalud.org)
  • Blocking macrophage colony-stimulating factor by using anti-c-Fms antibody also inhibited osteoclast formation and tooth movement . (bvsalud.org)
  • Silibinin was shown to powerfully stimulate osteoblastic bone formation and inhibit osteoclast bone destruction. (newsmax.com)
  • Furthermore, SFII inhibited osteoclast formation and bone loss in an inflammation- or ovariectomy-induced osteolytic mouse model. (ewha.ac.kr)
  • The intensity and pattern of osteoclast reactivity were similar to those of foreign-body type macrophage polykaryons in inflammatory lesions. (ox.ac.uk)
  • Osteoclasts are large, multinucleated cells that are produced by the fusion of mononuclear hematopoietic stem cells derived from the monocyte-macrophage lineage (osteoclastogenesis). (nature.com)
  • 2003). Nevertheless bone resorbing osteoclasts (OCL) of myeloid origin were shown to play an essential role in mobilizing the HSC from their niche in response to injury or stress (Kollet et al. (uea.ac.uk)
  • To investigate how osteoclasts develop around implanted OCP, we examined osteoclast differentiation using OCP crystals in vitro. (elsevier.com)
  • These results favour derivation of osteoclasts and their precursors from the multipotential haemopoietic stem cell which produces peripheral blood leucocytes and argues against their origin from a separate stem cell. (ox.ac.uk)
  • In a mouse model of orthodontic tooth movement , TNF-α was expressed and osteoclasts appeared on the compressed side of the periodontal ligament . (bvsalud.org)
  • Expression of dendritic cell-specific transmembrane protein (DC-STAMP), a critical player in osteoclast fusion, was significantly attenuated, and cell fusion of Sbno2-deficient osteoclasts was rescued by DC-STAMP. (monash.edu)
  • Further, addition of bone morphogenetic protein-2 significantly increased the number of osteoclasts in the OCP-coated wells. (elsevier.com)
  • Since osteoclasts play an active role in primary bone tumors and bone metastases, the use of anti-osteoclastic agents significantly reduces the mortality and morbidity rates of patients by preventing the progression and local spread of tumors. (por-journal.com)
  • Moreover, breast cancer cells stimulate IL-6 secretion by osteoclasts that is one of the factors known to supports osteoclastogenesis. (unifg.it)
  • SFII has therapeutic potential in the treatment and prevention of bone diseases caused by excessive osteoclast activity. (ewha.ac.kr)
  • Other mechanisms include a nitric oxide-dependent mechanism, in which magnesium directly affects osteoblast activity and number of osteoclasts. (nutraingredients.com)
  • however, markers of osteoblastic activity rise only slightly, whereas osteoclasts have a significant increase in their activity, peaking at 10 weeks following the injury with values 10 times the upper limits of normal (ULN). (medscape.com)
  • Alendronate does not interfere with osteoclast recruitment or attachment, but it does inhibit osteoclast activity. (rxdrugnews.com)
  • Preventive CCL2/CCR2 Axis Blockade Suppresses Osteoclast Activity in a Mouse Model of Rheumatoid Arthritis by Reducing Homing of CCR2hi Osteoclast Progenitors to the Affected Bone. (hdf.hr)
  • Colony Stimulating Factor 1(CSF1) is known to promote osteoclast progenitor survival but its role in osteoclast differentiation and mature osteoclast function are less well understood. (divbiolchem.org)
  • Two recent studies identified numerous multinucleated osteoclast-like cells expressing osteoclast phenotypic markers such as cathepsin K, CD51, and tartrate-resistant acid phosphatase (TRAP) within tophi and at the interface between bone and soft tissue [ 6 , 7 ]. (hindawi.com)
  • The number of cells that differentiated into osteoclasts was quantified. (imrpress.com)
  • IMSEAR at SEARO: Anaplastic thyroid carcinoma with osteoclast-like giant cells. (who.int)
  • Valand AG, Ramraje SN, Pandeya BS, Shedge R, Aware S. Anaplastic thyroid carcinoma with osteoclast-like giant cells. (who.int)
  • A case of anaplastic thyroid carcinoma with osteoclast-like giant cells is reported. (who.int)
  • Pleomorphic cells and tumour giant cells were accompanied by numerous osteoclast-like multinucleated giant cells. (who.int)
  • Furthermore, pepstatin A also suppressed differentiation from pre-osteoclast cells to mononuclear osteoclast cells dose-dependently. (elsevier.com)
  • B cells have a secondary role of increasing production of osteoclasts-specialized cells that break down bone material. (eyetheory.com)
  • Reorganization of the podosome into the sealing zone is crucial for osteoclasts (OCLs) to resorb bone, but the underlying mechanisms are unclear. (edu.au)
  • Studies on the role of osteoclasts (OCLs) in tumor biology have accelerated in recent years, and OCL inhibitors have been successfully used to treat metastatic cancers, especially breast cancer, multiple myeloma, and various diseases such as osteosarcoma, giant cell bone tumor, and aneurysmal bone cyst. (por-journal.com)
  • These results suggest that sodium salicylate has an inhibitory effect on the recruitment of osteoclast-like MNCs and that this inhibition is greater during the later stage of mouse bone marrow culture. (ui.ac.id)
  • However, Sbno2-deficient mice exhibited increased bone mass due to impaired osteoclast fusion. (monash.edu)
  • Remarkably, transgenic mice expressing the GSK3β-S9A mutant show an osteopetrotic phenotype due to impaired osteoclast differentiation. (elsevier.com)
  • In TNF-receptor-deficient mice , there was less tooth movement and osteoclast numbers were lower than in wild-type mice . (bvsalud.org)
  • Compared to saline treatments, bone-resorbing osteoclasts and bone marrow osteoclast precursor populations were also increased in ODE-treated WT but not IL-6 KO mice. (cdc.gov)
  • Studies in mice on the localization of radioactive [ 3 H]alendronate in bone showed about 10-fold higher uptake on osteoclast surfaces than on osteoblast surfaces. (rxdrugnews.com)
  • The precise mechanisms of OCP biodegradation remain unclear, though histological observations have revealed that bone-resorbing osteoclasts appear and resorb implanted OCP. (elsevier.com)
  • Histological examination using hematoxylin and eosin staining demonstrated an increased number of osteocytes and a decreased number of osteoclasts, but there was no significant increase in osteoblast numbers. (innovareacademics.in)
  • Bone is specialized connective tissue with a calcified extracellular matrix (bone matrix) and 3 major cell types: the osteoblast, osteocyte, and osteoclast. (moviecultists.com)
  • and osteoclasts, which dissolve calcium, thus weakening the bone. (newsmax.com)
  • Calcium intake reduces the degenerative effects of osteoclasts, which cause bone destruction as we age. (natnutra.com)
  • Cell attachment was labeled with monoclonal antibody 23C6, specific for a binding domain of a key osteoclast attachment protein, the CD51/CD61 integrin dimer (alpha(v)beta(3)), with or without cell permeabilization. (ox.ac.uk)
  • This cell, the osteoclast, is responsible for removing bone. (speakschmeak.com)
  • The group discovered that DNA methyltransferase, a type of enzyme, increases osteoclast, a cell that destroys bone tissues, and that TF-3 works to block the function of the enzyme. (saveourbones.com)
  • NO inhibits or kills osteoclasts, but the mechanism of action of NO in human bone turnover is not clear. (ox.ac.uk)
  • Rissanen JP, Ylipahkala H, Fagerlund KM, Long C, Väänänen HK, Halleen JM 2009 Improved methods for testing antiresorptive compounds in human osteoclast cultures . (oncobone.com)