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.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
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.
Metabolic bone diseases are a group of disorders that affect the bones' structure and strength, caused by disturbances in the normal metabolic processes involved in bone formation, resorption, or mineralization, including conditions like osteoporosis, osteomalacia, Paget's disease, and renal osteodystrophy.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
Tartrates are salts or esters of tartaric acid, primarily used in pharmaceutical industry as buffering agents, and in medical laboratories for the precipitation of proteins.
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.
Inbred ICR mice are a strain of albino laboratory mice that have been selectively bred for consistent genetic makeup and high reproductive performance, making them widely used in biomedical research for studies involving reproduction, toxicology, pharmacology, and carcinogenesis.
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)

Osteoclasts are large, multinucleated cells that are primarily responsible for bone resorption, a process in which they break down and dissolve the mineralized matrix of bones. They are derived from monocyte-macrophage precursor cells of hematopoietic origin and play a crucial role in maintaining bone homeostasis by balancing bone formation and bone resorption.

Osteoclasts adhere to the bone surface and create an isolated microenvironment, called the "resorption lacuna," between their cell membrane and the bone surface. Here, they release hydrogen ions into the lacuna through a process called proton pumping, which lowers the pH and dissolves the mineral component of the bone matrix. Additionally, osteoclasts secrete proteolytic enzymes, such as cathepsin K, that degrade the organic components, like collagen, in the bone matrix.

An imbalance in osteoclast activity can lead to various bone diseases, including osteoporosis and Paget's disease, where excessive bone resorption results in weakened and fragile bones.

Bone resorption is the process by which bone tissue is broken down and absorbed into the body. It is a normal part of bone remodeling, in which old or damaged bone tissue is removed and new tissue is formed. However, excessive bone resorption can lead to conditions such as osteoporosis, in which bones become weak and fragile due to a loss of density. This process is carried out by cells called osteoclasts, which break down the bone tissue and release minerals such as calcium into the bloodstream.

REceptor Activator of NF-kB (RANK) Ligand is a type of protein that plays a crucial role in the immune system and bone metabolism. It belongs to the tumor necrosis factor (TNF) superfamily and is primarily produced by osteoblasts, which are cells responsible for bone formation.

RANK Ligand binds to its receptor RANK, which is found on the surface of osteoclasts, a type of cell involved in bone resorption or breakdown. The binding of RANK Ligand to RANK activates signaling pathways that promote the differentiation, activation, and survival of osteoclasts, thereby increasing bone resorption.

Abnormalities in the RANKL-RANK signaling pathway have been implicated in various bone diseases, such as osteoporosis, rheumatoid arthritis, and certain types of cancer that metastasize to bones. Therefore, targeting this pathway with therapeutic agents has emerged as a promising approach for the treatment of these conditions.

Receptor Activator of Nuclear Factor-kappa B (RANK) is a type I transmembrane protein and a member of the tumor necrosis factor receptor superfamily. It plays a crucial role in the regulation of bone metabolism through the activation of osteoclasts, which are cells responsible for bone resorption.

When RANK binds to its ligand, RANKL (Receptor Activator of Nuclear Factor-kappa B Ligand), it triggers a series of intracellular signaling events that lead to the activation and differentiation of osteoclast precursors into mature osteoclasts. This process is essential for maintaining bone homeostasis, as excessive osteoclast activity can result in bone loss and diseases such as osteoporosis.

In addition to its role in bone metabolism, RANK has also been implicated in the regulation of immune responses, as it is involved in the activation and differentiation of dendritic cells and T cells. Dysregulation of RANK signaling has been associated with various pathological conditions, including autoimmune diseases and cancer.

Osteopetrosis, also known as Albers-Schönberg disease or marble bone disease, is a group of rare genetic disorders characterized by increased bone density due to impaired bone resorption by osteoclasts. This results in brittle bones that are more susceptible to fractures and can also lead to various complications such as anemia, hearing loss, and vision problems. There are several types of osteopetrosis, which vary in severity and age of onset.

The medical definition of osteopetrosis is:

A genetic disorder characterized by defective bone resorption due to impaired osteoclast function, resulting in increased bone density, susceptibility to fractures, and potential complications such as anemia, hearing loss, and vision problems.

Acid phosphatase is a type of enzyme that is found in various tissues and organs throughout the body, including the prostate gland, red blood cells, bone, liver, spleen, and kidneys. This enzyme plays a role in several biological processes, such as bone metabolism and the breakdown of molecules like nucleotides and proteins.

Acid phosphatase is classified based on its optimum pH level for activity. Acid phosphatases have an optimal activity at acidic pH levels (below 7.0), while alkaline phosphatases have an optimal activity at basic or alkaline pH levels (above 7.0).

In clinical settings, measuring the level of acid phosphatase in the blood can be useful as a tumor marker for prostate cancer. Elevated acid phosphatase levels may indicate the presence of metastatic prostate cancer or disease progression. However, it is important to note that acid phosphatase is not specific to prostate cancer and can also be elevated in other conditions, such as bone diseases, liver disorders, and some benign conditions. Therefore, acid phosphatase should be interpreted in conjunction with other diagnostic tests and clinical findings for a more accurate diagnosis.

Osteoprotegerin (OPG) is a soluble decoy receptor for the receptor activator of nuclear factor kappa-B ligand (RANKL). It is a member of the tumor necrosis factor (TNF) receptor superfamily and plays a crucial role in regulating bone metabolism. By binding to RANKL, OPG prevents it from interacting with its signaling receptor RANK on the surface of osteoclast precursor cells, thereby inhibiting osteoclast differentiation, activation, and survival. This results in reduced bone resorption and increased bone mass.

In addition to its role in bone homeostasis, OPG has also been implicated in various physiological and pathological processes, including immune regulation, cancer progression, and cardiovascular disease.

Cathepsin K is a proteolytic enzyme, which belongs to the family of papain-like cysteine proteases. It is primarily produced by osteoclasts, which are specialized cells responsible for bone resorption. Cathepsin K plays a crucial role in the degradation and remodeling of the extracellular matrix, particularly in bone tissue.

This enzyme is capable of breaking down various proteins, including collagen, elastin, and proteoglycans, which are major components of the bone matrix. By doing so, cathepsin K helps osteoclasts to dissolve and remove mineralized and non-mineralized bone matrix during the process of bone resorption.

Apart from its function in bone metabolism, cathepsin K has also been implicated in several pathological conditions, such as osteoporosis, rheumatoid arthritis, and tumor metastasis to bones. Inhibitors of cathepsin K are being investigated as potential therapeutic agents for the treatment of these disorders.

"Bone" is the hard, dense connective tissue that makes up the skeleton of vertebrate animals. It provides support and protection for the body's internal organs, and serves as a attachment site for muscles, tendons, and ligaments. Bone is composed of cells called osteoblasts and osteoclasts, which are responsible for bone formation and resorption, respectively, and an extracellular matrix made up of collagen fibers and mineral crystals.

Bones can be classified into two main types: compact bone and spongy bone. Compact bone is dense and hard, and makes up the outer layer of all bones and the shafts of long bones. Spongy bone is less dense and contains large spaces, and makes up the ends of long bones and the interior of flat and irregular bones.

The human body has 206 bones in total. They can be further classified into five categories based on their shape: long bones, short bones, flat bones, irregular bones, and sesamoid bones.

Osteoblasts are specialized bone-forming cells that are derived from mesenchymal stem cells. They play a crucial role in the process of bone formation and remodeling. Osteoblasts synthesize, secrete, and mineralize the organic matrix of bones, which is mainly composed of type I collagen.

These cells have receptors for various hormones and growth factors that regulate their activity, such as parathyroid hormone, vitamin D, and transforming growth factor-beta. When osteoblasts are not actively producing bone matrix, they can become trapped within the matrix they produce, where they differentiate into osteocytes, which are mature bone cells that play a role in maintaining bone structure and responding to mechanical stress.

Abnormalities in osteoblast function can lead to various bone diseases, such as osteoporosis, osteogenesis imperfecta, and Paget's disease of bone.

Macrophage Colony-Stimulating Factor (M-CSF) is a growth factor that belongs to the family of colony-stimulating factors (CSFs). It is a glycoprotein hormone that plays a crucial role in the survival, proliferation, and differentiation of mononuclear phagocytes, including macrophages. M-CSF binds to its receptor, CSF1R, which is expressed on the surface of monocytes, macrophages, and their precursors.

M-CSF stimulates the production of mature macrophages from monocyte precursors in the bone marrow and enhances the survival and function of mature macrophages in peripheral tissues. It also promotes the activation of macrophages, increasing their ability to phagocytize and destroy foreign particles, microorganisms, and tumor cells.

In addition to its role in the immune system, M-CSF has been implicated in various physiological processes, including hematopoiesis, bone remodeling, angiogenesis, and female reproduction. Dysregulation of M-CSF signaling has been associated with several pathological conditions, such as inflammatory diseases, autoimmune disorders, and cancer.

Cell differentiation is the process by which a less specialized cell, or stem cell, becomes a more specialized cell type with specific functions and structures. This process involves changes in gene expression, which are regulated by various intracellular signaling pathways and transcription factors. Differentiation results in the development of distinct cell types that make up tissues and organs in multicellular organisms. It is a crucial aspect of embryonic development, tissue repair, and maintenance of homeostasis in the body.

Bone remodeling is the normal and continuous process by which bone tissue is removed from the skeleton (a process called resorption) and new bone tissue is formed (a process called formation). This ongoing cycle allows bones to repair microdamage, adjust their size and shape in response to mechanical stress, and maintain mineral homeostasis. The cells responsible for bone resorption are osteoclasts, while the cells responsible for bone formation are osteoblasts. These two cell types work together to maintain the structural integrity and health of bones throughout an individual's life.

During bone remodeling, the process can be divided into several stages:

1. Activation: The initiation of bone remodeling is triggered by various factors such as microdamage, hormonal changes, or mechanical stress. This leads to the recruitment and activation of osteoclast precursor cells.
2. Resorption: Osteoclasts attach to the bone surface and create a sealed compartment called a resorption lacuna. They then secrete acid and enzymes that dissolve and digest the mineralized matrix, creating pits or cavities on the bone surface. This process helps remove old or damaged bone tissue and releases calcium and phosphate ions into the bloodstream.
3. Reversal: After resorption is complete, the osteoclasts undergo apoptosis (programmed cell death), and mononuclear cells called reversal cells appear on the resorbed surface. These cells prepare the bone surface for the next stage by cleaning up debris and releasing signals that attract osteoblast precursors.
4. Formation: Osteoblasts, derived from mesenchymal stem cells, migrate to the resorbed surface and begin producing a new organic matrix called osteoid. As the osteoid mineralizes, it forms a hard, calcified structure that gradually replaces the resorbed bone tissue. The osteoblasts may become embedded within this newly formed bone as they differentiate into osteocytes, which are mature bone cells responsible for maintaining bone homeostasis and responding to mechanical stress.
5. Mineralization: Over time, the newly formed bone continues to mineralize, becoming stronger and more dense. This process helps maintain the structural integrity of the skeleton and ensures adequate calcium storage.

Throughout this continuous cycle of bone remodeling, hormones, growth factors, and mechanical stress play crucial roles in regulating the balance between resorption and formation. Disruptions to this delicate equilibrium can lead to various bone diseases, such as osteoporosis, where excessive resorption results in weakened bones and increased fracture risk.

Osteolysis is a medical term that refers to the loss or resorption of bone tissue. It's a process where the body's normal bone remodeling cycle is disrupted, leading to an imbalance between bone formation and bone breakdown. This results in the progressive deterioration and destruction of bone.

Osteolysis can occur due to various reasons such as chronic inflammation, mechanical stress, or certain medical conditions like rheumatoid arthritis, Paget's disease, or bone tumors. It can also be a side effect of some medications, such as those used in cancer treatment or for managing osteoporosis.

In severe cases, osteolysis can lead to weakened bones, increased risk of fractures, and deformities. Treatment typically aims to address the underlying cause and may include medication, surgery, or lifestyle changes.

Osteogenesis is the process of bone formation or development. It involves the differentiation and maturation of osteoblasts, which are bone-forming cells that synthesize and deposit the organic matrix of bone tissue, composed mainly of type I collagen. This organic matrix later mineralizes to form the inorganic crystalline component of bone, primarily hydroxyapatite.

There are two primary types of osteogenesis: intramembranous and endochondral. Intramembranous osteogenesis occurs directly within connective tissue, where mesenchymal stem cells differentiate into osteoblasts and form bone tissue without an intervening cartilage template. This process is responsible for the formation of flat bones like the skull and clavicles.

Endochondral osteogenesis, on the other hand, involves the initial development of a cartilaginous model or template, which is later replaced by bone tissue. This process forms long bones, such as those in the limbs, and occurs through several stages involving chondrocyte proliferation, hypertrophy, and calcification, followed by invasion of blood vessels and osteoblasts to replace the cartilage with bone tissue.

Abnormalities in osteogenesis can lead to various skeletal disorders and diseases, such as osteogenesis imperfecta (brittle bone disease), achondroplasia (a form of dwarfism), and cleidocranial dysplasia (a disorder affecting skull and collarbone development).

Bone marrow cells are the types of cells found within the bone marrow, which is the spongy tissue inside certain bones in the body. The main function of bone marrow is to produce blood cells. There are two types of bone marrow: red and yellow. Red bone marrow is where most blood cell production takes place, while yellow bone marrow serves as a fat storage site.

The three main types of bone marrow cells are:

1. Hematopoietic stem cells (HSCs): These are immature cells that can differentiate into any type of blood cell, including red blood cells, white blood cells, and platelets. They have the ability to self-renew, meaning they can divide and create more hematopoietic stem cells.
2. Red blood cell progenitors: These are immature cells that will develop into mature red blood cells, also known as erythrocytes. Red blood cells carry oxygen from the lungs to the body's tissues and carbon dioxide back to the lungs.
3. Myeloid and lymphoid white blood cell progenitors: These are immature cells that will develop into various types of white blood cells, which play a crucial role in the body's immune system by fighting infections and diseases. Myeloid progenitors give rise to granulocytes (neutrophils, eosinophils, and basophils), monocytes, and megakaryocytes (which eventually become platelets). Lymphoid progenitors differentiate into B cells, T cells, and natural killer (NK) cells.

Bone marrow cells are essential for maintaining a healthy blood cell count and immune system function. Abnormalities in bone marrow cells can lead to various medical conditions, such as anemia, leukopenia, leukocytosis, thrombocytopenia, or thrombocytosis, depending on the specific type of blood cell affected. Additionally, bone marrow cells are often used in transplantation procedures to treat patients with certain types of cancer, such as leukemia and lymphoma, or other hematologic disorders.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Nuclear factor of activated T-cells (NFAT) transcription factors are a group of proteins that play a crucial role in the regulation of gene transcription in various cells, including immune cells. They are involved in the activation of genes responsible for immune responses, cell survival, differentiation, and development.

NFAT transcription factors can be divided into five main members: NFATC1 (also known as NFAT2 or NFATp), NFATC2 (or NFAT1), NFATC3 (or NFATc), NFATC4 (or NFAT3), and NFAT5 (or TonEBP). These proteins share a highly conserved DNA-binding domain, known as the Rel homology region, which allows them to bind to specific sequences in the promoter or enhancer regions of target genes.

NFATC transcription factors are primarily located in the cytoplasm in their inactive form, bound to inhibitory proteins. Upon stimulation of the cell, typically through calcium-dependent signaling pathways, NFAT proteins get dephosphorylated by calcineurin phosphatase, leading to their nuclear translocation and activation. Once in the nucleus, NFATC transcription factors can form homodimers or heterodimers with other transcription factors, such as AP-1, to regulate gene expression.

In summary, NFATC transcription factors are a family of proteins involved in the regulation of gene transcription, primarily in immune cells, and play critical roles in various cellular processes, including immune responses, differentiation, and development.

Vacuolar Proton-Translocating ATPases (V-ATPases) are complex enzyme systems that are found in the membranes of various intracellular organelles, such as vacuoles, endosomes, lysosomes, and Golgi apparatus. They play a crucial role in the establishment and maintenance of electrochemical gradients across these membranes by actively pumping protons (H+) from the cytosol to the lumen of the organelles.

The V-ATPases are composed of two major components: a catalytic domain, known as V1, which contains multiple subunits and is responsible for ATP hydrolysis; and a membrane-bound domain, called V0, which consists of several subunits and facilitates proton translocation. The energy generated from ATP hydrolysis in the V1 domain is used to drive conformational changes in the V0 domain, resulting in the vectorial transport of protons across the membrane.

These electrochemical gradients established by V-ATPases are essential for various cellular processes, including secondary active transport, maintenance of organellar pH, protein sorting and trafficking, and regulation of cell volume. Dysfunction in V-ATPases has been implicated in several human diseases, such as neurodegenerative disorders, renal tubular acidosis, and certain types of cancer.

Membrane glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide backbone. They are integral components of biological membranes, spanning the lipid bilayer and playing crucial roles in various cellular processes.

The glycosylation of these proteins occurs in the endoplasmic reticulum (ER) and Golgi apparatus during protein folding and trafficking. The attached glycans can vary in structure, length, and composition, which contributes to the diversity of membrane glycoproteins.

Membrane glycoproteins can be classified into two main types based on their orientation within the lipid bilayer:

1. Type I (N-linked): These glycoproteins have a single transmembrane domain and an extracellular N-terminus, where the oligosaccharides are predominantly attached via asparagine residues (Asn-X-Ser/Thr sequon).
2. Type II (C-linked): These glycoproteins possess two transmembrane domains and an intracellular C-terminus, with the oligosaccharides linked to tryptophan residues via a mannose moiety.

Membrane glycoproteins are involved in various cellular functions, such as:

* Cell adhesion and recognition
* Receptor-mediated signal transduction
* Enzymatic catalysis
* Transport of molecules across membranes
* Cell-cell communication
* Immunological responses

Some examples of membrane glycoproteins include cell surface receptors (e.g., growth factor receptors, cytokine receptors), adhesion molecules (e.g., integrins, cadherins), and transporters (e.g., ion channels, ABC transporters).

Osteocytes are the most abundant cell type in mature bone tissue. They are star-shaped cells that are located inside the mineralized matrix of bones, with their processes extending into small spaces called lacunae and canaliculi. Osteocytes are derived from osteoblasts, which are bone-forming cells that become trapped within the matrix they produce.

Osteocytes play a crucial role in maintaining bone homeostasis by regulating bone remodeling, sensing mechanical stress, and modulating mineralization. They communicate with each other and with osteoblasts and osteoclasts (bone-resorbing cells) through a network of interconnected processes and via the release of signaling molecules. Osteocytes can also respond to changes in their environment, such as hormonal signals or mechanical loading, by altering their gene expression and releasing factors that regulate bone metabolism.

Dysfunction of osteocytes has been implicated in various bone diseases, including osteoporosis, osteogenesis imperfecta, and Paget's disease of bone.

Diphosphonates are a class of medications that are used to treat bone diseases, such as osteoporosis and Paget's disease. They work by binding to the surface of bones and inhibiting the activity of bone-resorbing cells called osteoclasts. This helps to slow down the breakdown and loss of bone tissue, which can help to reduce the risk of fractures.

Diphosphonates are typically taken orally in the form of tablets, but some forms may be given by injection. Commonly prescribed diphosphonates include alendronate (Fosamax), risedronate (Actonel), and ibandronate (Boniva). Side effects of diphosphonates can include gastrointestinal symptoms such as nausea, heartburn, and abdominal pain. In rare cases, they may also cause esophageal ulcers or osteonecrosis of the jaw.

It is important to follow the instructions for taking diphosphonates carefully, as they must be taken on an empty stomach with a full glass of water and the patient must remain upright for at least 30 minutes after taking the medication to reduce the risk of esophageal irritation. Regular monitoring of bone density and kidney function is also recommended while taking these medications.

Calcitonin is a hormone that is produced and released by the parafollicular cells (also known as C cells) of the thyroid gland. It plays a crucial role in regulating calcium homeostasis in the body. Specifically, it helps to lower elevated levels of calcium in the blood by inhibiting the activity of osteoclasts, which are bone cells that break down bone tissue and release calcium into the bloodstream. Calcitonin also promotes the uptake of calcium in the bones and increases the excretion of calcium in the urine.

Calcitonin is typically released in response to high levels of calcium in the blood, and its effects help to bring calcium levels back into balance. In addition to its role in calcium regulation, calcitonin may also have other functions in the body, such as modulating immune function and reducing inflammation.

Clinically, synthetic forms of calcitonin are sometimes used as a medication to treat conditions related to abnormal calcium levels, such as hypercalcemia (high blood calcium) or osteoporosis. Calcitonin can be administered as an injection, nasal spray, or oral tablet, depending on the specific formulation and intended use.

The skull is the bony structure that encloses and protects the brain, the eyes, and the ears. It is composed of two main parts: the cranium, which contains the brain, and the facial bones. The cranium is made up of several fused flat bones, while the facial bones include the upper jaw (maxilla), lower jaw (mandible), cheekbones, nose bones, and eye sockets (orbits).

The skull also provides attachment points for various muscles that control chewing, moving the head, and facial expressions. Additionally, it contains openings for blood vessels, nerves, and the spinal cord to pass through. The skull's primary function is to protect the delicate and vital structures within it from injury and trauma.

Bone development, also known as ossification, is the process by which bone tissue is formed and grows. This complex process involves several different types of cells, including osteoblasts, which produce new bone matrix, and osteoclasts, which break down and resorb existing bone tissue.

There are two main types of bone development: intramembranous and endochondral ossification. Intramembranous ossification occurs when bone tissue forms directly from connective tissue, while endochondral ossification involves the formation of a cartilage model that is later replaced by bone.

During fetal development, most bones develop through endochondral ossification, starting as a cartilage template that is gradually replaced by bone tissue. However, some bones, such as those in the skull and clavicles, develop through intramembranous ossification.

Bone development continues after birth, with new bone tissue being laid down and existing tissue being remodeled throughout life. This ongoing process helps to maintain the strength and integrity of the skeleton, allowing it to adapt to changing mechanical forces and repair any damage that may occur.

Bone matrix refers to the non-cellular component of bone that provides structural support and functions as a reservoir for minerals, such as calcium and phosphate. It is made up of organic and inorganic components. The organic component consists mainly of type I collagen fibers, which provide flexibility and tensile strength to the bone. The inorganic component is primarily composed of hydroxyapatite crystals, which give bone its hardness and compressive strength. Bone matrix also contains other proteins, growth factors, and signaling molecules that regulate bone formation, remodeling, and repair.

Carrier proteins, also known as transport proteins, are a type of protein that facilitates the movement of molecules across cell membranes. They are responsible for the selective and active transport of ions, sugars, amino acids, and other molecules from one side of the membrane to the other, against their concentration gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate).

Carrier proteins have a specific binding site for the molecule they transport, and undergo conformational changes upon binding, which allows them to move the molecule across the membrane. Once the molecule has been transported, the carrier protein returns to its original conformation, ready to bind and transport another molecule.

Carrier proteins play a crucial role in maintaining the balance of ions and other molecules inside and outside of cells, and are essential for many physiological processes, including nerve impulse transmission, muscle contraction, and nutrient uptake.

Osteoporosis is a systemic skeletal disease characterized by low bone mass, deterioration of bone tissue, and disruption of bone architecture, leading to increased risk of fractures, particularly in the spine, wrist, and hip. It mainly affects older people, especially postmenopausal women, due to hormonal changes that reduce bone density. Osteoporosis can also be caused by certain medications, medical conditions, or lifestyle factors such as smoking, alcohol abuse, and a lack of calcium and vitamin D in the diet. The diagnosis is often made using bone mineral density testing, and treatment may include medication to slow bone loss, promote bone formation, and prevent fractures.

Tumor Necrosis Factor (TNF) Receptors are cell surface receptors that bind to tumor necrosis factor cytokines. They play crucial roles in the regulation of a variety of immune cell functions, including inflammation, immunity, and cell survival or death (apoptosis).

There are two major types of TNF receptors: TNFR1 (also known as p55 or CD120a) and TNFR2 (also known as p75 or CD120b). TNFR1 is widely expressed in most tissues, while TNFR2 has a more restricted expression pattern and is mainly found on immune cells.

TNF receptors have an intracellular domain called the death domain, which can trigger signaling pathways leading to apoptosis when activated by TNF ligands. However, they can also activate other signaling pathways that promote cell survival, differentiation, and inflammation. Dysregulation of TNF receptor signaling has been implicated in various diseases, including cancer, autoimmune disorders, and neurodegenerative conditions.

Cathepsins are a type of proteolytic enzymes, which are found in lysosomes and are responsible for breaking down proteins inside the cell. They are classified as papain-like cysteine proteases and play important roles in various physiological processes, including tissue remodeling, antigen presentation, and apoptosis (programmed cell death). There are several different types of cathepsins, including cathepsin B, C, D, F, H, K, L, S, V, and X/Z, each with distinct substrate specificities and functions.

Dysregulation of cathepsins has been implicated in various pathological conditions, such as cancer, neurodegenerative diseases, and inflammatory disorders. For example, overexpression or hyperactivation of certain cathepsins has been shown to contribute to tumor invasion and metastasis, while their inhibition has been explored as a potential therapeutic strategy in cancer treatment. Similarly, abnormal levels of cathepsins have been linked to the progression of neurodegenerative diseases like Alzheimer's and Parkinson's, making them attractive targets for drug development.

The term "Receptor, Macrophage Colony-Stimulating Factor" refers to a specific type of receptor found on the surface of certain cells, particularly macrophages and other cells involved in the immune response. This receptor binds to a protein called Macrophage Colony-Stimulating Factor (M-CSF), which is a growth factor that plays an important role in the proliferation, differentiation, and survival of mononuclear phagocytes, including macrophages.

Macrophages are key players in the immune system, responsible for engulfing and destroying foreign particles, microbes, and tumor cells. M-CSF receptor (also known as CSF1R or CD115) binds to M-CSF and activates a series of intracellular signaling pathways that promote the survival, proliferation, and differentiation of macrophages and their precursors.

Abnormalities in the M-CSF/M-CSF receptor signaling pathway have been implicated in various diseases, including cancer, inflammatory disorders, and autoimmune diseases. Therefore, targeting this pathway has emerged as a potential therapeutic strategy for these conditions.

Bone neoplasms are abnormal growths or tumors that develop in the bone. They can be benign (non-cancerous) or malignant (cancerous). Benign bone neoplasms do not spread to other parts of the body and are rarely a threat to life, although they may cause problems if they grow large enough to press on surrounding tissues or cause fractures. Malignant bone neoplasms, on the other hand, can invade and destroy nearby tissue and may spread (metastasize) to other parts of the body.

There are many different types of bone neoplasms, including:

1. Osteochondroma - a benign tumor that develops from cartilage and bone
2. Enchondroma - a benign tumor that forms in the cartilage that lines the inside of the bones
3. Chondrosarcoma - a malignant tumor that develops from cartilage
4. Osteosarcoma - a malignant tumor that develops from bone cells
5. Ewing sarcoma - a malignant tumor that develops in the bones or soft tissues around the bones
6. Giant cell tumor of bone - a benign or occasionally malignant tumor that develops from bone tissue
7. Fibrosarcoma - a malignant tumor that develops from fibrous tissue in the bone

The symptoms of bone neoplasms vary depending on the type, size, and location of the tumor. They may include pain, swelling, stiffness, fractures, or limited mobility. Treatment options depend on the type and stage of the tumor but may include surgery, radiation therapy, chemotherapy, or a combination of these treatments.

Isoenzymes, also known as isoforms, are multiple forms of an enzyme that catalyze the same chemical reaction but differ in their amino acid sequence, structure, and/or kinetic properties. They are encoded by different genes or alternative splicing of the same gene. Isoenzymes can be found in various tissues and organs, and they play a crucial role in biological processes such as metabolism, detoxification, and cell signaling. Measurement of isoenzyme levels in body fluids (such as blood) can provide valuable diagnostic information for certain medical conditions, including tissue damage, inflammation, and various diseases.

Bone density conservation agents, also known as anti-resorptive agents or bone-sparing drugs, are a class of medications that help to prevent the loss of bone mass and reduce the risk of fractures. They work by inhibiting the activity of osteoclasts, the cells responsible for breaking down and reabsorbing bone tissue during the natural remodeling process.

Examples of bone density conservation agents include:

1. Bisphosphonates (e.g., alendronate, risedronate, ibandronate, zoledronic acid) - These are the most commonly prescribed class of bone density conservation agents. They bind to hydroxyapatite crystals in bone tissue and inhibit osteoclast activity, thereby reducing bone resorption.
2. Denosumab (Prolia) - This is a monoclonal antibody that targets RANKL (Receptor Activator of Nuclear Factor-κB Ligand), a key signaling molecule involved in osteoclast differentiation and activation. By inhibiting RANKL, denosumab reduces osteoclast activity and bone resorption.
3. Selective estrogen receptor modulators (SERMs) (e.g., raloxifene) - These medications act as estrogen agonists or antagonists in different tissues. In bone tissue, SERMs mimic the bone-preserving effects of estrogen by inhibiting osteoclast activity and reducing bone resorption.
4. Hormone replacement therapy (HRT) - Estrogen hormone replacement therapy has been shown to preserve bone density in postmenopausal women; however, its use is limited due to increased risks of breast cancer, cardiovascular disease, and thromboembolic events.
5. Calcitonin - This hormone, secreted by the thyroid gland, inhibits osteoclast activity and reduces bone resorption. However, it has largely been replaced by other more effective bone density conservation agents.

These medications are often prescribed for individuals at high risk of fractures due to conditions such as osteoporosis or metabolic disorders that affect bone health. It is essential to follow the recommended dosage and administration guidelines to maximize their benefits while minimizing potential side effects. Regular monitoring of bone density, blood calcium levels, and other relevant parameters is also necessary during treatment with these medications.

Bone density refers to the amount of bone mineral content (usually measured in grams) in a given volume of bone (usually measured in cubic centimeters). It is often used as an indicator of bone strength and fracture risk. Bone density is typically measured using dual-energy X-ray absorptiometry (DXA) scans, which provide a T-score that compares the patient's bone density to that of a young adult reference population. A T-score of -1 or above is considered normal, while a T-score between -1 and -2.5 indicates osteopenia (low bone mass), and a T-score below -2.5 indicates osteoporosis (porous bones). Regular exercise, adequate calcium and vitamin D intake, and medication (if necessary) can help maintain or improve bone density and prevent fractures.

C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.

The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.

C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.

One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.

Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Alendronate is a medication that falls under the class of bisphosphonates. It is commonly used in the treatment and prevention of osteoporosis in postmenopausal women and men, as well as in the management of glucocorticoid-induced osteoporosis and Paget's disease of bone.

Alendronate works by inhibiting the activity of osteoclasts, which are cells responsible for breaking down and reabsorbing bone tissue. By reducing the activity of osteoclasts, alendronate helps to slow down bone loss and increase bone density, thereby reducing the risk of fractures.

The medication is available in several forms, including tablets and oral solutions, and is typically taken once a week for osteoporosis prevention and treatment. It is important to follow the dosing instructions carefully, as improper administration can reduce the drug's effectiveness or increase the risk of side effects. Common side effects of alendronate include gastrointestinal symptoms such as heartburn, stomach pain, and nausea.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

Bone diseases is a broad term that refers to various medical conditions that affect the bones. These conditions can be categorized into several groups, including:

1. Developmental and congenital bone diseases: These are conditions that affect bone growth and development before or at birth. Examples include osteogenesis imperfecta (brittle bone disease), achondroplasia (dwarfism), and cleidocranial dysostosis.
2. Metabolic bone diseases: These are conditions that affect the body's ability to maintain healthy bones. They are often caused by hormonal imbalances, vitamin deficiencies, or problems with mineral metabolism. Examples include osteoporosis, osteomalacia, and Paget's disease of bone.
3. Inflammatory bone diseases: These are conditions that cause inflammation in the bones. They can be caused by infections, autoimmune disorders, or other medical conditions. Examples include osteomyelitis, rheumatoid arthritis, and ankylosing spondylitis.
4. Degenerative bone diseases: These are conditions that cause the bones to break down over time. They can be caused by aging, injury, or disease. Examples include osteoarthritis, avascular necrosis, and diffuse idiopathic skeletal hyperostosis (DISH).
5. Tumors and cancers of the bone: These are conditions that involve abnormal growths in the bones. They can be benign or malignant. Examples include osteosarcoma, chondrosarcoma, and Ewing sarcoma.
6. Fractures and injuries: While not strictly a "disease," fractures and injuries are common conditions that affect the bones. They can result from trauma, overuse, or weakened bones. Examples include stress fractures, compound fractures, and dislocations.

Overall, bone diseases can cause a wide range of symptoms, including pain, stiffness, deformity, and decreased mobility. Treatment for these conditions varies depending on the specific diagnosis but may include medication, surgery, physical therapy, or lifestyle changes.

Coculture techniques refer to a type of experimental setup in which two or more different types of cells or organisms are grown and studied together in a shared culture medium. This method allows researchers to examine the interactions between different cell types or species under controlled conditions, and to study how these interactions may influence various biological processes such as growth, gene expression, metabolism, and signal transduction.

Coculture techniques can be used to investigate a wide range of biological phenomena, including the effects of host-microbe interactions on human health and disease, the impact of different cell types on tissue development and homeostasis, and the role of microbial communities in shaping ecosystems. These techniques can also be used to test the efficacy and safety of new drugs or therapies by examining their effects on cells grown in coculture with other relevant cell types.

There are several different ways to establish cocultures, depending on the specific research question and experimental goals. Some common methods include:

1. Mixed cultures: In this approach, two or more cell types are simply mixed together in a culture dish or flask and allowed to grow and interact freely.
2. Cell-layer cultures: Here, one cell type is grown on a porous membrane or other support structure, while the second cell type is grown on top of it, forming a layered coculture.
3. Conditioned media cultures: In this case, one cell type is grown to confluence and its culture medium is collected and then used to grow a second cell type. This allows the second cell type to be exposed to any factors secreted by the first cell type into the medium.
4. Microfluidic cocultures: These involve growing cells in microfabricated channels or chambers, which allow for precise control over the spatial arrangement and flow of nutrients, waste products, and signaling molecules between different cell types.

Overall, coculture techniques provide a powerful tool for studying complex biological systems and gaining insights into the mechanisms that underlie various physiological and pathological processes.

Macrophages are a type of white blood cell that are an essential part of the immune system. They are large, specialized cells that engulf and destroy foreign substances, such as bacteria, viruses, parasites, and fungi, as well as damaged or dead cells. Macrophages are found throughout the body, including in the bloodstream, lymph nodes, spleen, liver, lungs, and connective tissues. They play a critical role in inflammation, immune response, and tissue repair and remodeling.

Macrophages originate from monocytes, which are a type of white blood cell produced in the bone marrow. When monocytes enter the tissues, they differentiate into macrophages, which have a larger size and more specialized functions than monocytes. Macrophages can change their shape and move through tissues to reach sites of infection or injury. They also produce cytokines, chemokines, and other signaling molecules that help coordinate the immune response and recruit other immune cells to the site of infection or injury.

Macrophages have a variety of surface receptors that allow them to recognize and respond to different types of foreign substances and signals from other cells. They can engulf and digest foreign particles, bacteria, and viruses through a process called phagocytosis. Macrophages also play a role in presenting antigens to T cells, which are another type of immune cell that helps coordinate the immune response.

Overall, macrophages are crucial for maintaining tissue homeostasis, defending against infection, and promoting wound healing and tissue repair. Dysregulation of macrophage function has been implicated in a variety of diseases, including cancer, autoimmune disorders, and chronic inflammatory conditions.

Osteitis deformans, also known as Paget's disease of bone, is a chronic disorder of the bone characterized by abnormal turnover and remodeling of the bone. In this condition, the bone becomes enlarged, thickened, and deformed due to excessive and disorganized bone formation and resorption.

The process begins when the bone-remodeling cycle is disrupted, leading to an imbalance between the activity of osteoclasts (cells that break down bone) and osteoblasts (cells that form new bone). In Paget's disease, osteoclasts become overactive and increase bone resorption, followed by an overzealous response from osteoblasts, which attempt to repair the damage but do so in a disorganized manner.

The affected bones can become weakened, prone to fractures, and may cause pain, deformities, or other complications such as arthritis, hearing loss, or neurological symptoms if the skull or spine is involved. The exact cause of Paget's disease remains unknown, but it is believed that genetic and environmental factors play a role in its development.

Early diagnosis and treatment can help manage the symptoms and prevent complications associated with osteitis deformans. Treatment options include medications to slow down bone turnover, pain management, and orthopedic interventions when necessary.

Metabolic bone diseases are a group of conditions that affect the bones and are caused by disorders in the body's metabolism. These disorders can result in changes to the bone structure, density, and strength, leading to an increased risk of fractures and other complications. Some common examples of metabolic bone diseases include:

1. Osteoporosis: a condition characterized by weak and brittle bones that are more likely to break, often as a result of age-related bone loss or hormonal changes.
2. Paget's disease of bone: a chronic disorder that causes abnormal bone growth and deformities, leading to fragile and enlarged bones.
3. Osteomalacia: a condition caused by a lack of vitamin D or problems with the body's ability to absorb it, resulting in weak and soft bones.
4. Hyperparathyroidism: a hormonal disorder that causes too much parathyroid hormone to be produced, leading to bone loss and other complications.
5. Hypoparathyroidism: a hormonal disorder that results in low levels of parathyroid hormone, causing weak and brittle bones.
6. Renal osteodystrophy: a group of bone disorders that occur as a result of chronic kidney disease, including osteomalacia, osteoporosis, and high turnover bone disease.

Treatment for metabolic bone diseases may include medications to improve bone density and strength, dietary changes, exercise, and lifestyle modifications. In some cases, surgery may be necessary to correct bone deformities or fractures.

According to the National Institutes of Health (NIH), stem cells are "initial cells" or "precursor cells" that have the ability to differentiate into many different cell types in the body. They can also divide without limit to replenish other cells for as long as the person or animal is still alive.

There are two main types of stem cells: embryonic stem cells, which come from human embryos, and adult stem cells, which are found in various tissues throughout the body. Embryonic stem cells have the ability to differentiate into all cell types in the body, while adult stem cells have more limited differentiation potential.

Stem cells play an essential role in the development and repair of various tissues and organs in the body. They are currently being studied for their potential use in the treatment of a wide range of diseases and conditions, including cancer, diabetes, heart disease, and neurological disorders. However, more research is needed to fully understand the properties and capabilities of these cells before they can be used safely and effectively in clinical settings.

Tartrates are salts or esters of tartaric acid, a naturally occurring organic acid found in many fruits, particularly grapes. In a medical context, potassium bitartrate (also known as cream of tartar) is sometimes used as a mild laxative or to treat acidosis by helping to restore the body's normal pH balance. Additionally, sodium tartrate has been historically used as an antidote for lead poisoning. However, these uses are not common in modern medicine.

Cytoplasmic receptors and nuclear receptors are two types of intracellular receptors that play crucial roles in signal transduction pathways and regulation of gene expression. They are classified based on their location within the cell. Here are the medical definitions for each:

1. Cytoplasmic Receptors: These are a group of intracellular receptors primarily found in the cytoplasm of cells, which bind to specific hormones, growth factors, or other signaling molecules. Upon binding, these receptors undergo conformational changes that allow them to interact with various partners, such as adapter proteins and enzymes, leading to activation of downstream signaling cascades. These pathways ultimately result in modulation of cellular processes like proliferation, differentiation, and apoptosis. Examples of cytoplasmic receptors include receptor tyrosine kinases (RTKs), serine/threonine kinase receptors, and cytokine receptors.
2. Nuclear Receptors: These are a distinct class of intracellular receptors that reside primarily in the nucleus of cells. They bind to specific ligands, such as steroid hormones, thyroid hormones, vitamin D, retinoic acid, and various other lipophilic molecules. Upon binding, nuclear receptors undergo conformational changes that facilitate their interaction with co-regulatory proteins and the DNA. This interaction results in the modulation of gene transcription, ultimately leading to alterations in protein expression and cellular responses. Examples of nuclear receptors include estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR), thyroid hormone receptor (TR), vitamin D receptor (VDR), and peroxisome proliferator-activated receptors (PPARs).

Both cytoplasmic and nuclear receptors are essential components of cellular communication networks, allowing cells to respond appropriately to extracellular signals and maintain homeostasis. Dysregulation of these receptors has been implicated in various diseases, including cancer, diabetes, and autoimmune disorders.

TNF Receptor-Associated Factor 6 (TRAF6) is a protein that plays a crucial role in the signaling pathways of various cytokine receptors and pattern recognition receptors, including TNF receptors, IL-1 receptors, and TLRs. It functions as an E3 ubiquitin ligase, which adds ubiquitin molecules to other proteins, thereby modulating their activity, stability, or localization.

TRAF6 is involved in the activation of several downstream signaling pathways, such as NF-κB and MAPK pathways, leading to the induction of immune responses, inflammation, cell survival, differentiation, and proliferation. Mutations or dysregulation of TRAF6 have been implicated in various diseases, including immunodeficiencies, autoimmune disorders, and cancers.

X-ray microtomography, often referred to as micro-CT, is a non-destructive imaging technique used to visualize and analyze the internal structure of objects with high spatial resolution. It is based on the principles of computed tomography (CT), where multiple X-ray images are acquired at different angles and then reconstructed into cross-sectional slices using specialized software. These slices can be further processed to create 3D visualizations, allowing researchers and clinicians to examine the internal structure and composition of samples in great detail. Micro-CT is widely used in materials science, biology, medicine, and engineering for various applications such as material characterization, bone analysis, and defect inspection.

Parathyroid hormone (PTH) is a polypeptide hormone that plays a crucial role in the regulation of calcium and phosphate levels in the body. It is produced and secreted by the parathyroid glands, which are four small endocrine glands located on the back surface of the thyroid gland.

The primary function of PTH is to maintain normal calcium levels in the blood by increasing calcium absorption from the gut, mobilizing calcium from bones, and decreasing calcium excretion by the kidneys. PTH also increases phosphate excretion by the kidneys, which helps to lower serum phosphate levels.

In addition to its role in calcium and phosphate homeostasis, PTH has been shown to have anabolic effects on bone tissue, stimulating bone formation and preventing bone loss. However, chronic elevations in PTH levels can lead to excessive bone resorption and osteoporosis.

Overall, Parathyroid Hormone is a critical hormone that helps maintain mineral homeostasis and supports healthy bone metabolism.

Osteopontin (OPN) is a phosphorylated glycoprotein that is widely distributed in many tissues, including bone, teeth, and mineralized tissues. It plays important roles in various biological processes such as bone remodeling, immune response, wound healing, and tissue repair. In the skeletal system, osteopontin is involved in the regulation of bone formation and resorption by modulating the activity of osteoclasts and osteoblasts. It also plays a role in the development of chronic inflammatory diseases such as rheumatoid arthritis, atherosclerosis, and cancer metastasis to bones. Osteopontin is considered a potential biomarker for various disease states, including bone turnover, cardiovascular disease, and cancer progression.

Glycoproteins are complex proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide backbone. These glycans are linked to the protein through asparagine residues (N-linked) or serine/threonine residues (O-linked). Glycoproteins play crucial roles in various biological processes, including cell recognition, cell-cell interactions, cell adhesion, and signal transduction. They are widely distributed in nature and can be found on the outer surface of cell membranes, in extracellular fluids, and as components of the extracellular matrix. The structure and composition of glycoproteins can vary significantly depending on their function and location within an organism.

The femur is the medical term for the thigh bone, which is the longest and strongest bone in the human body. It connects the hip bone to the knee joint and plays a crucial role in supporting the weight of the body and allowing movement during activities such as walking, running, and jumping. The femur is composed of a rounded head, a long shaft, and two condyles at the lower end that articulate with the tibia and patella to form the knee joint.

Calcitriol is the active form of vitamin D, also known as 1,25-dihydroxyvitamin D. It is a steroid hormone that plays a crucial role in regulating calcium and phosphate levels in the body to maintain healthy bones. Calcitriol is produced in the kidneys from its precursor, calcidiol (25-hydroxyvitamin D), which is derived from dietary sources or synthesized in the skin upon exposure to sunlight.

Calcitriol promotes calcium absorption in the intestines, helps regulate calcium and phosphate levels in the kidneys, and stimulates bone cells (osteoblasts) to form new bone tissue while inhibiting the activity of osteoclasts, which resorb bone. This hormone is essential for normal bone mineralization and growth, as well as for preventing hypocalcemia (low calcium levels).

In addition to its role in bone health, calcitriol has various other physiological functions, including modulating immune responses, cell proliferation, differentiation, and apoptosis. Calcitriol deficiency or resistance can lead to conditions such as rickets in children and osteomalacia or osteoporosis in adults.

Physiologic calcification is the normal deposit of calcium salts in body tissues and organs. It is a natural process that occurs as part of the growth and development of the human body, as well as during the repair and remodeling of tissues.

Calcium is an essential mineral that plays a critical role in many bodily functions, including bone formation, muscle contraction, nerve impulse transmission, and blood clotting. In order to maintain proper levels of calcium in the body, excess calcium that is not needed for these functions may be deposited in various tissues as a normal part of the aging process.

Physiologic calcification typically occurs in areas such as the walls of blood vessels, the lungs, and the heart valves. While these calcifications are generally harmless, they can sometimes lead to complications, particularly if they occur in large amounts or in sensitive areas. For example, calcification of the coronary arteries can increase the risk of heart disease, while calcification of the lung tissue can cause respiratory symptoms.

It is important to note that pathologic calcification, on the other hand, refers to the abnormal deposit of calcium salts in tissues and organs, which can be caused by various medical conditions such as chronic kidney disease, hyperparathyroidism, and certain infections. Pathologic calcification is not a normal process and can lead to serious health complications if left untreated.

Monocyte-macrophage precursor cells, also known as monoblasts or macrophage dendritic cell progenitors, are a type of white blood cell that gives rise to both monocytes and macrophages. They are found in the bone marrow and are part of the immune system's early defense against infection. Monocyte-macrophage precursor cells are large cells with a round or oval nucleus, and they are characterized by the expression of specific surface markers such as CD14 and CD16. They have the ability to differentiate into monocytes, which then circulate in the blood and can further differentiate into macrophages or dendritic cells, depending on the signals they receive from their environment. Macrophages are important phagocytic cells that engulf and destroy foreign particles, microbes, and cellular debris, while dendritic cells play a key role in antigen presentation to T-cells and activation of the adaptive immune response.

Integrin β3 is a subunit of certain integrin heterodimers, which are transmembrane receptors that mediate cell-cell and cell-extracellular matrix (ECM) adhesion. Integrin β3 combines with either integrin αv (to form the integrin αvβ3) or integrin αIIb (to form the integrin αIIbβ3). These integrins are involved in various cellular processes, including platelet aggregation, angiogenesis, and tumor metastasis.

Integrin αIIbβ3 is primarily expressed on platelets and mediates platelet aggregation by binding to fibrinogen, von Willebrand factor, and other adhesive proteins in the ECM. Integrin αvβ3 is widely expressed in various cell types and participates in diverse functions such as cell migration, proliferation, differentiation, and survival. It binds to a variety of ECM proteins, including fibronectin, vitronectin, and osteopontin, as well as to soluble ligands like vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β).

Dysregulation of integrin β3 has been implicated in several pathological conditions, such as thrombosis, atherosclerosis, tumor metastasis, and inflammatory diseases.

The tibia, also known as the shin bone, is the larger of the two bones in the lower leg and part of the knee joint. It supports most of the body's weight and is a major insertion point for muscles that flex the foot and bend the leg. The tibia articulates with the femur at the knee joint and with the fibula and talus bone at the ankle joint. Injuries to the tibia, such as fractures, are common in sports and other activities that put stress on the lower leg.

Vitronectin receptors, also known as integrin αvβ3 or integrin avb3, are a type of cell surface receptor that bind to the protein vitronectin. These receptors are heterodimeric transmembrane proteins composed of αv and β3 subunits. They play important roles in various biological processes including cell adhesion, migration, proliferation, and survival. Vitronectin receptors are widely expressed in many different cell types, including endothelial cells, smooth muscle cells, and platelets. In addition to vitronectin, these receptors can also bind to other extracellular matrix proteins such as fibronectin, von Willebrand factor, and osteopontin. They are also involved in the regulation of angiogenesis, wound healing, and bone metabolism.

Cell fusion is the process by which two or more cells combine to form a single cell with a single nucleus, containing the genetic material from all of the original cells. This can occur naturally in certain biological processes, such as fertilization (when a sperm and egg cell fuse to form a zygote), muscle development (where multiple muscle precursor cells fuse together to create multinucleated muscle fibers), and during the formation of bone (where osteoclasts, the cells responsible for breaking down bone tissue, are multinucleated).

Cell fusion can also be induced artificially in laboratory settings through various methods, including chemical treatments, electrical stimulation, or viral vectors. Induced cell fusion is often used in research to create hybrid cells with unique properties, such as cybrid cells (cytoplasmic hybrids) and heterokaryons (nuclear hybrids). These hybrid cells can help scientists study various aspects of cell biology, genetics, and disease mechanisms.

In summary, cell fusion is the merging of two or more cells into one, resulting in a single cell with combined genetic material. This process occurs naturally during certain biological processes and can be induced artificially for research purposes.

Proto-oncogene proteins, such as c-Fos, are normal cellular proteins that play crucial roles in various biological processes including cell growth, differentiation, and survival. They can be activated or overexpressed due to genetic alterations, leading to the formation of cancerous cells. The c-Fos protein is a nuclear phosphoprotein involved in signal transduction pathways and forms a heterodimer with c-Jun to create the activator protein-1 (AP-1) transcription factor complex. This complex binds to specific DNA sequences, thereby regulating the expression of target genes that contribute to various cellular responses, including proliferation, differentiation, and apoptosis. Dysregulation of c-Fos can result in uncontrolled cell growth and malignant transformation, contributing to tumor development and progression.

Monocytes are a type of white blood cell that are part of the immune system. They are large cells with a round or oval shape and a nucleus that is typically indented or horseshoe-shaped. Monocytes are produced in the bone marrow and then circulate in the bloodstream, where they can differentiate into other types of immune cells such as macrophages and dendritic cells.

Monocytes play an important role in the body's defense against infection and tissue damage. They are able to engulf and digest foreign particles, microorganisms, and dead or damaged cells, which helps to clear them from the body. Monocytes also produce cytokines, which are signaling molecules that help to coordinate the immune response.

Elevated levels of monocytes in the bloodstream can be a sign of an ongoing infection, inflammation, or other medical conditions such as cancer or autoimmune disorders.

Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is a laboratory technique used in molecular biology to amplify and detect specific DNA sequences. This technique is particularly useful for the detection and quantification of RNA viruses, as well as for the analysis of gene expression.

The process involves two main steps: reverse transcription and polymerase chain reaction (PCR). In the first step, reverse transcriptase enzyme is used to convert RNA into complementary DNA (cDNA) by reading the template provided by the RNA molecule. This cDNA then serves as a template for the PCR amplification step.

In the second step, the PCR reaction uses two primers that flank the target DNA sequence and a thermostable polymerase enzyme to repeatedly copy the targeted cDNA sequence. The reaction mixture is heated and cooled in cycles, allowing the primers to anneal to the template, and the polymerase to extend the new strand. This results in exponential amplification of the target DNA sequence, making it possible to detect even small amounts of RNA or cDNA.

RT-PCR is a sensitive and specific technique that has many applications in medical research and diagnostics, including the detection of viruses such as HIV, hepatitis C virus, and SARS-CoV-2 (the virus that causes COVID-19). It can also be used to study gene expression, identify genetic mutations, and diagnose genetic disorders.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

The Microphthalmia-Associated Transcription Factor (MITF) is a protein that functions as a transcription factor, which means it regulates the expression of specific genes. It belongs to the basic helix-loop-helix leucine zipper (bHLH-Zip) family of transcription factors and plays crucial roles in various biological processes such as cell growth, differentiation, and survival.

MITF is particularly well-known for its role in the development and function of melanocytes, the pigment-producing cells found in the skin, eyes, and inner ear. It regulates the expression of genes involved in melanin synthesis and thus influences hair and skin color. Mutations in the MITF gene have been associated with certain eye disorders, including microphthalmia (small or underdeveloped eyes), iris coloboma (a gap or hole in the iris), and Waardenburg syndrome type 2A (an inherited disorder characterized by hearing loss and pigmentation abnormalities).

In addition to its role in melanocytes, MITF also plays a part in the development and function of other cell types, including osteoclasts (cells involved in bone resorption), mast cells (immune cells involved in allergic reactions), and retinal pigment epithelial cells (a type of cell found in the eye).

Osteosclerosis is a medical term that refers to an abnormal thickening and increased density of bone tissue. This condition can occur as a result of various diseases or conditions, such as certain types of bone cancer, Paget's disease of bone, fluoride poisoning, or chronic infection of the bone. Osteosclerosis can also be seen in some benign conditions, such as osteopetrosis, which is a rare genetic disorder characterized by an excessively hard and dense skeleton.

In some cases, osteosclerosis may not cause any symptoms and may only be discovered on X-rays or other imaging studies. However, in other cases, it can lead to complications such as bone pain, fractures, or deformities. Treatment for osteosclerosis depends on the underlying cause of the condition and may include medications, surgery, or other therapies.

Giant cells are large, multinucleated cells that result from the fusion of monocytes or macrophages. They can be found in various types of inflammatory and degenerative lesions, including granulomas, which are a hallmark of certain diseases such as tuberculosis and sarcoidosis. There are several types of giant cells, including:

1. Langhans giant cells: These have a horseshoe-shaped or crescentic arrangement of nuclei around the periphery of the cell. They are typically found in granulomas associated with infectious diseases such as tuberculosis and histoplasmosis.
2. Foreign body giant cells: These form in response to the presence of foreign material, such as a splinter or suture, in tissue. The nuclei are usually scattered throughout the cell cytoplasm.
3. Touton giant cells: These are found in certain inflammatory conditions, such as xanthomatosis and granulomatous slack skin. They have a central core of lipid-laden histiocytes surrounded by a ring of nuclei.
4. Osteoclast giant cells: These are multinucleated cells responsible for bone resorption. They can be found in conditions such as giant cell tumors of bone and Paget's disease.

It is important to note that the presence of giant cells alone does not necessarily indicate a specific diagnosis, and their significance must be interpreted within the context of the overall clinical and pathological findings.

NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) is a protein complex that plays a crucial role in regulating the immune response to infection and inflammation, as well as in cell survival, differentiation, and proliferation. It is composed of several subunits, including p50, p52, p65 (RelA), c-Rel, and RelB, which can form homodimers or heterodimers that bind to specific DNA sequences called κB sites in the promoter regions of target genes.

Under normal conditions, NF-κB is sequestered in the cytoplasm by inhibitory proteins known as IκBs (inhibitors of κB). However, upon stimulation by various signals such as cytokines, bacterial or viral products, and stress, IκBs are phosphorylated, ubiquitinated, and degraded, leading to the release and activation of NF-κB. Activated NF-κB then translocates to the nucleus, where it binds to κB sites and regulates the expression of target genes involved in inflammation, immunity, cell survival, and proliferation.

Dysregulation of NF-κB signaling has been implicated in various pathological conditions such as cancer, chronic inflammation, autoimmune diseases, and neurodegenerative disorders. Therefore, targeting NF-κB signaling has emerged as a potential therapeutic strategy for the treatment of these diseases.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Dentin is the hard, calcified tissue that lies beneath the enamel and cementum of a tooth. It forms the majority of the tooth's structure and is composed primarily of mineral salts (hydroxyapatite), collagenous proteins, and water. Dentin has a tubular structure, with microscopic channels called dentinal tubules that radiate outward from the pulp chamber (the center of the tooth containing nerves and blood vessels) to the exterior of the tooth. These tubules contain fluid and nerve endings that are responsible for the tooth's sensitivity to various stimuli such as temperature changes, pressure, or decay. Dentin plays a crucial role in protecting the dental pulp while also providing support and structure to the overlying enamel and cementum.

Transgenic mice are genetically modified rodents that have incorporated foreign DNA (exogenous DNA) into their own genome. This is typically done through the use of recombinant DNA technology, where a specific gene or genetic sequence of interest is isolated and then introduced into the mouse embryo. The resulting transgenic mice can then express the protein encoded by the foreign gene, allowing researchers to study its function in a living organism.

The process of creating transgenic mice usually involves microinjecting the exogenous DNA into the pronucleus of a fertilized egg, which is then implanted into a surrogate mother. The offspring that result from this procedure are screened for the presence of the foreign DNA, and those that carry the desired genetic modification are used to establish a transgenic mouse line.

Transgenic mice have been widely used in biomedical research to model human diseases, study gene function, and test new therapies. They provide a valuable tool for understanding complex biological processes and developing new treatments for a variety of medical conditions.

ICR (Institute of Cancer Research) is a strain of albino Swiss mice that are widely used in scientific research. They are an outbred strain, which means that they have been bred to maintain maximum genetic heterogeneity. However, it is also possible to find inbred strains of ICR mice, which are genetically identical individuals produced by many generations of brother-sister mating.

Inbred ICR mice are a specific type of ICR mouse that has been inbred for at least 20 generations. This means that they have a high degree of genetic uniformity and are essentially genetically identical to one another. Inbred strains of mice are often used in research because their genetic consistency makes them more reliable models for studying biological phenomena and testing new therapies or treatments.

It is important to note that while inbred ICR mice may be useful for certain types of research, they do not necessarily represent the genetic diversity found in human populations. Therefore, it is important to consider the limitations of using any animal model when interpreting research findings and applying them to human health.

Cell survival refers to the ability of a cell to continue living and functioning normally, despite being exposed to potentially harmful conditions or treatments. This can include exposure to toxins, radiation, chemotherapeutic drugs, or other stressors that can damage cells or interfere with their normal processes.

In scientific research, measures of cell survival are often used to evaluate the effectiveness of various therapies or treatments. For example, researchers may expose cells to a particular drug or treatment and then measure the percentage of cells that survive to assess its potential therapeutic value. Similarly, in toxicology studies, measures of cell survival can help to determine the safety of various chemicals or substances.

It's important to note that cell survival is not the same as cell proliferation, which refers to the ability of cells to divide and multiply. While some treatments may promote cell survival, they may also inhibit cell proliferation, making them useful for treating diseases such as cancer. Conversely, other treatments may be designed to specifically target and kill cancer cells, even if it means sacrificing some healthy cells in the process.

Ovariectomy is a surgical procedure in which one or both ovaries are removed. It is also known as "ovary removal" or "oophorectomy." This procedure is often performed as a treatment for various medical conditions, including ovarian cancer, endometriosis, uterine fibroids, and pelvic pain. Ovariectomy can also be part of a larger surgical procedure called an hysterectomy, in which the uterus is also removed.

In some cases, an ovariectomy may be performed as a preventative measure for individuals at high risk of developing ovarian cancer. This is known as a prophylactic ovariectomy. After an ovariectomy, a person will no longer have menstrual periods and will be unable to become pregnant naturally. Hormone replacement therapy may be recommended in some cases to help manage symptoms associated with the loss of hormones produced by the ovaries.

Giant cell tumors (GCTs) are a type of benign or rarely malignant bone tumor that is characterized by the presence of multinucleated giant cells. These tumors typically affect adults between the ages of 20 and 40, and they can occur in any bone, but they most commonly involve the long bones near the knee joint.

GCTs are composed of three types of cells: mononuclear stromal cells, which produce the matrix of the tumor; multinucleated osteoclast-like giant cells, which resemble the bone-resorbing cells found in normal bone; and macrophages, which are part of the body's immune system.

The mononuclear stromal cells produce a variety of growth factors that stimulate the formation and activity of the osteoclast-like giant cells, leading to localized bone destruction. The tumor may cause pain, swelling, and limited mobility in the affected area.

While GCTs are typically benign, they can be aggressive and locally destructive, with a tendency to recur after surgical removal. In some cases, GCTs may undergo malignant transformation, leading to the development of sarcomas. Treatment options for GCTs include curettage (scraping out) of the tumor, followed by bone grafting or the use of a cement spacer to fill the defect, and/or adjuvant therapy with radiation or chemotherapy.

"Cell count" is a medical term that refers to the process of determining the number of cells present in a given volume or sample of fluid or tissue. This can be done through various laboratory methods, such as counting individual cells under a microscope using a specialized grid called a hemocytometer, or using automated cell counters that use light scattering and electrical impedance techniques to count and classify different types of cells.

Cell counts are used in a variety of medical contexts, including hematology (the study of blood and blood-forming tissues), microbiology (the study of microscopic organisms), and pathology (the study of diseases and their causes). For example, a complete blood count (CBC) is a routine laboratory test that includes a white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin level, hematocrit value, and platelet count. Abnormal cell counts can indicate the presence of various medical conditions, such as infections, anemia, or leukemia.

'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.

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... is a protein that in humans is encoded by the OCSTAMP gene. GRCh38: Ensembl ... "Entrez Gene: Osteoclast stimulatory transmembrane protein". Retrieved 2016-07-24. v t e (Articles with short description, Short ...
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 ...
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): ...
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 tuberculosis, herpes, or HIV, or as part of a foreign body ... Osteoclasts are a type of MGC that are critical for the maintenance, repair, and remodeling of bone and are present normally in ... Osteoclasts are the most prominent examples of MGCs and are responsible for the resorption of bones in the body. Like other ...
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 ...
... multinucleated osteoclasts in bone tissues; 8) kidney podocytes; and 9) cells in the nervous system, e.g., microglia cells in ...
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- ...
... reabsorption by osteoclasts, and remodeling by osteoblasts. Osteoclasts precursor cells and mature osteoclast require ... Increased CSF-1 promotes proliferation of osteoclasts and osteoclast precursors and increases osteoclast bone reabsorption. ... CSF1R signaling also directly regulates osteoclast function. Osteoclasts migrate along the bone surface, then adhere to the ... Osteoclast are multi-nucleated cells that that absorb and remove bone which is critical for growth of new bones and maintenance ...
Mun SH, Park PS, Park-Min KH (August 2020). "The M-CSF receptor in osteoclasts and beyond". Experimental & Molecular Medicine. ...
... osteoblasts and osteoclasts); and taste receptor-bearing cells in the tongue's taste buds. FFAR1 is also expressed in 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 ...
An osteoclast is a large multinucleated cell and human osteoclasts on bone typically have four nuclei and are 150-200 µm in ... Osteoclasts are found on those surfaces of bone that are undergoing resorption. On such surfaces, the osteoclasts are seen to ... In bone, osteoclasts are found in pits in the bone surface which are called resorption bays, or Howships lacunae. Osteoclasts ... When osteoclast-inducing cytokines are used to convert macrophages to osteoclasts, very large cells that may reach 100 µm in ...
Explore the RANK signaling pathway in osteoclasts and find antibodies to detect some of its target proteins, including CD254, ... are activated by RANK in osteoclasts or osteoclast precursors [4]. JNK1, and not JNK2, is important for efficient osteoclast ... Events that occur after RANK stimulation in differentiated osteoclasts or osteoclast precursor cells include the ... and they are essential for the development and activation of osteoclasts [1]. RANKL induces the differentiation of osteoclast ...
DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features. J Exp Med. 2003 Aug 18;198(4): ...
These results indicate that osteoclasts or cells closely related to osteoclasts form in long-term human bone marrow cultures. ... Osteoclast-like cells form in long-term human bone marrow but not in peripheral blood cultures.. ... Osteoclast-like cells form in long-term human bone marrow but not in peripheral blood cultures.. ... Thus we tested the capacity of peripheral blood monocytes to form osteoclasts in long-term culture. We have reported previously ...
Giant osteoclasts in patients under bisphosphonates. In: BMC clinical pathology, 2014, vol. 14, n° Article 31. doi: 10.1186/ ...
Osteoclasts cultured on Ca3ZrSi2O9 expressed increased levels of osteoclast-related genes; Cathepsin K, Carbonic Anhydrase II, ... Osteoclasts cultured on Ca3ZrSi2O9 expressed increased levels of osteoclast-related genes; Cathepsin K, Carbonic Anhydrase II, ... Osteoclasts cultured on Ca3ZrSi2O9 expressed increased levels of osteoclast-related genes; Cathepsin K, Carbonic Anhydrase II, ... Osteoclasts cultured on Ca3ZrSi2O9 expressed increased levels of osteoclast-related genes; Cathepsin K, Carbonic Anhydrase II, ...
To elucidate the role of JAK2 in osteoclasts, we generated an osteoclast-specific JAK2-KO (Oc-JAK2-KO) mouse using the Cre/Lox- ... To directly assess the role of osteoclast-derived IGF1, we generated an osteoclast-specific IGF1-KO mouse, which showed a ... Interestingly, Oc-JAK2-KO mice had reduced osteoclast-specific expression of IGF1, suggesting a role for osteoclast-derived ... Osteoclasts are specialized cells of the hematopoietic lineage that are responsible for bone resorption and play a critical ...
We studied osteoclast differentiation from mouse-derived isolated monocyte precursors and bone resorption by mature osteoclasts ... We studied osteoclast differentiation from mouse-derived isolated monocyte precursors and bone resorption by mature osteoclasts ... Osteoclast gene expression and resorption during spaceflight. TAMMA R;COLAIANNI G;CAMERINO, CLAUDIA;DI BENEDETTO A;GRECO G; ... These evidences indicate osteoclasts as direct target of mechanical forces and further address future studies to the ...
The implications of these results for osteoclast ontogeny, the nature of the antigens described and the question of osteoclast- ... The epitopes recognized by these antibodies are thus not osteoclast-specific and are present on other cells of the mononuclear ... Both antibodies reacted with several cell types apart from osteoclasts including megakaryocytes, smooth muscle cells, ... The immunohistochemical profile of osteoclast-reacting monoclonal antibodies, 13C2 and 23C6, known to detect the alpha-chain of ...
Drugs for osteoclasts. Bisphosphonates, or drugs that slow down bone cells called osteoclasts, can be used to alleviate pain ... Since osteoclasts can become overactive in advanced prostate cancer that has spread to the bones, these help slow the growth of ... Similar to bisphosphonates, denosumab can also be used to block osteoclasts and help prevent fractures. This drug is injected ...
Connective Tissue Cells - Osteoclasts PubMed MeSh Term *Overview. Overview. subject area of * A CTGF-RUNX2-RANKL Axis in Breast ...
Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and ... stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro ...
We show that α2,3- and α2,6-linked sialic acids have a role in the process of osteoclast differentiation. OPN is one of the ... Osteoclasts secrete osteopontin into resorption lacunae during bone resorption. Luukkonen, Jani; Hilli, Meeri; Nakamura, Miho; ... It is believed to be one of the key components in osteoclast attachment to bone during resorption. In this study, we ... Our data further confirm that osteoclasts secrete OPN into the resorption pit where it may function as a chemokine for ...
Reduce Osteoclast Activity. Several medications directly decrease the activity of osteoclasts. Bone resorption inhibitors ... 10, 11, 12, 13] This medication acts by inhibiting osteoclast-mediated resorption and by reducing osteoclast viability. The ...
Estrogen regulation of gene expression in osteoblasts and osteoclasts. / Oursler, Merry Jo. In: Critical Reviews in Eukaryotic ... Oursler, M. J. (1998). Estrogen regulation of gene expression in osteoblasts and osteoclasts. Critical Reviews in Eukaryotic ... Oursler, MJ 1998, Estrogen regulation of gene expression in osteoblasts and osteoclasts, Critical Reviews in Eukaryotic Gene ... Estrogen regulation of gene expression in osteoblasts and osteoclasts. Critical Reviews in Eukaryotic Gene Expression. 1998;8(2 ...
Cellular Origin and Functions of Osteoclasts in Inflammatory Arthritis. Hannah Nelson1, Ellen Gravallese2, Julia Charles1 and ... Conclusion: These data suggest that both HSC-derived and EMOP-derived osteoclast precursor cells independently contribute to OC ... Nelson H, Gravallese E, Charles J, Jacome-Galarza C. Cellular Origin and Functions of Osteoclasts in Inflammatory Arthritis [ ... is an autoimmune disease targeting multiple joints and characterized by joint destruction caused by osteoclasts (OC), leading ...
In vitro induction and culture of osteoclasts with Ti-alloy particles MAO Yuan-qing, ZHU Zhen-an, TANG Ting-ting, YUAN Zhen, ... Objective To explore the method of in vitro induction and culture of mature mouse osteoclasts from macrophages with Ti-alloy ... Conclusion Mature mouse osteoclasts can be successfully induced and cultured in vitro from macrophages with Ti-alloy particles. ... The cultured cells subjected to tartrate-resistant acid phosphatase (TRAP) staining, and expressions of osteoclast specific ...
Agents that could inhibit osteoclast formation or function are regarded as promising alternatives to treat osteoclast-related ... Gastrodin Inhibits Osteoclasts Multiple Ways and Stimulates Mesenchymal Stem Cells In Vitro. Abstract. Gastrodin inhibits ... In this study, we investigated the effects of gastrodin on receptor activator NF-κB ligand (RANKL)-activated osteoclasts ... However, excessive activation of osteoclasts is responsible for many bone diseases such as osteoporosis, Paget disease, and ...
Grobogan-Indonesia Increased The Number of Osteoblasts and Osteocytes, Inhibited Osteoclast Damage in The Tibia Bone of Rats * ... In addition, the number of osteoclasts in the tibia bone of rats that were treated with tempe flour and soybean flour were ... Grobogan tempe flour and soybean flour on the profile of osteoblasts, osteocytes, and osteoclasts in the tibia bone of rats. ... The treatment using soybean flour (10% and 20%) or tempe flour (10% and 20%) decreased the number of osteoclasts in the tibia ...
Cannabinoids and Bone: Endocannabinoids modulate human osteoclast function in vitro. 2012 - Published. ...
... osteoclasts; mesenchymal stromal cells; non-canonical osteoclastogenesis; breast cancer; invasion; metastasis; ruthenium; CLDN6 ... osteoclasts; mesenchymal stromal cells; non-canonical osteoclastogenesis; breast cancer; invasion; metastasis; ruthenium; CLDN6 ...
... lineage cells in human bone were recently shown to colonize eroded bone surfaces and to closely interact with osteoclasts. They ... Herein, we used co-cultures of primary human osteoblast lineage cells and human osteoclasts derived from peripheral blood ... This close interaction results in a strong and significant increase in the bone resorptive activity of osteoclasts - especially ... Keywords: Bone resorption; Co-culture; MMP; MMP-13; Matrix metalloproteinase; Osteoclast; Reversal cell. ...
Osteoclasts are giant bone cells formed by fusion from monocytes and uniquely capable of a complete destruction of mineralized ... Previously, we have demonstrated that in energy-rich environment not only osteoclast fusion index (the number of nuclei each ... Regulation of Osteoclast Growth and Fusion by mTOR/raptor and mTOR/rictor/Akt. ... Regulation of Osteoclast Growth and Fusion by mTOR/raptor and mTOR/rictor/Akt ...
Variations in osteoclast cell number are observed when osteoclast precursor cells are irradiated with atmospheric dielectric ... abstract = "Variations in osteoclast cell number are observed when osteoclast precursor cells are irradiated with atmospheric ... N2 - Variations in osteoclast cell number are observed when osteoclast precursor cells are irradiated with atmospheric ... AB - Variations in osteoclast cell number are observed when osteoclast precursor cells are irradiated with atmospheric ...
The stiffness and collagen control differentiation of osteoclasts with an altered expression of c-Src in podosome ... The stiffness and collagen control differentiation of osteoclasts with an altered expression of c-Src in podosome ...
... was studied to determine the effects of ZA on angiogenic gene expression in primary human osteoclasts. Osteoclast cultures were ... Primary osteoclasts were found to express a number of key angiogenic molecules at very high levels. Gene expression levels for ... Effects of zoledronic acid and geranylgeraniol on angiogenic gene expression in primary human osteoclasts.. Zafar, Sobia; P ...
involved_in positive regulation of osteoclast differentiation IDA Inferred from Direct Assay. more info ...
TRAP Osteoclasts Per mm2 bone. 3. (. 5. ). a. 6. (. 5. ). b. 6. (. 5. ). b. 0.6. 0.01. ... TRAP positive osteoclasts were counted to quantify the number of osteoclasts within the metaphyseal region directly below the ... Greater osteoclast numbers were seen primarily within the metaphysic upon whole bone microscopic observation. Osteoclast ... A) vehicle control dose treated male with cathepsin K stained osteoclasts, inset photo illustrates an osteoclast stained ...
Additional file 2: of Radix Paeoniae Rubra stimulates osteoclast differentiation by activation of the NF-ÎşB and mitogen- ... Radix Paeoniae Rubra stimulates osteoclast differentiation by activation of the NF-ΚB and mitogen-activated protein kinase ... of Radix Paeoniae Rubra stimulates osteoclast differentiation by activation of the NF-ÎşB and mitogen-activated protein kinase ...
  • RANKL induces the differentiation of osteoclast precursor cells and stimulates the resorption function and survival of mature osteoclasts. (thermofisher.com)
  • JNK1, and not JNK2, is important for efficient osteoclast differentiation. (thermofisher.com)
  • DAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features. (alzforum.org)
  • We studied osteoclast differentiation from mouse-derived isolated monocyte precursors and bone resorption by mature osteoclasts, and found that microgravity directly stimulates osteoclastogenesis and increases bone resorption. (uniba.it)
  • This is followed by a more detailed examination of our present knowledge of estrogen effects on osteoblasts and the differentiation and activity of osteoclasts. (elsevierpure.com)
  • However, the direct action of gastrodin on osteoclast differentiation and bone resorption, and its underlying molecular mechanism, remain unknown. (osteoporosis-studies.com)
  • Our results showed that gastrodin retarded RANKL-induced osteoclast differentiation efficiently by downregulating transcriptional and translational expression of nuclear factor of activated T cells cl (NFATc1), a major factor in RANKL-mediated osteoclastogenesis. (osteoporosis-studies.com)
  • The response of human osteoblast like cells (HOB), osteoclast and endothelial cells when cultured on Ca 3 ZrSi 2 O 9 ceramics was investigated. (edu.au)
  • Estrogen effects on osteoblast and osteoclast gene expression are of critical importance in seeking to understand these contradictory influences. (elsevierpure.com)
  • Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. (ox.ac.uk)
  • Events that occur after RANK stimulation in differentiated osteoclasts or osteoclast precursor cells include the phosphorylation and degradation of I-kappaB-Alpha and the nuclear translocation and DNA binding of the NF-kappaB proteins p50, p52, and p65 [3]. (thermofisher.com)
  • The concept showing that osteoclasts are derived from a specific population (named osteoclast precursor cells [OCPs]) among myeloid cells has been long hypothesized. (e-jbm.org)
  • However, the specific precursor population of osteoclasts is not clearly defined yet. (e-jbm.org)
  • These data suggest that both HSC-derived and EMOP-derived osteoclast precursor cells independently contribute to OC formation in IA. (acrabstracts.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)
  • Osteoblasts and osteoclasts arise from distinct cell lineages and maturation processes, i.e., osteoblasts arise from mesenchymal stem cells, whereas osteoclasts differentiate from hematopoietic monocyte/macrophage precursors [1]. (thermofisher.com)
  • Oursler, MJ 1998, ' Estrogen regulation of gene expression in osteoblasts and osteoclasts ', Critical Reviews in Eukaryotic Gene Expression , vol. 8, no. 2, pp. 125-140. (elsevierpure.com)
  • Moreover, it has been well established that osteoclasts are differentiated in vitro from myeloid cells such as bone marrow macrophages or monocytes. (e-jbm.org)
  • 7 ] In addition, it has been shown that osteoclasts can be derived in vitro from cells of a myeloid origin, including human and mouse BM cells, splenic macrophages, and unfractionated, mature monocytes from human peripheral blood. (e-jbm.org)
  • Objective To explore the method of in vitro induction and culture of mature mouse osteoclasts from macrophages with Ti-alloy particles. (shsmu.edu.cn)
  • Conclusion Mature mouse osteoclasts can be successfully induced and cultured in vitro from macrophages with Ti-alloy particles. (shsmu.edu.cn)
  • In summary, gastrodin could prevent osteoclasts formation and bone resorption via blockage of NFATc1 activity, and stimulate osseointegration in vitro. (osteoporosis-studies.com)
  • Moreover, when CD34+ cells were differentiated in vitro, genetically corrected osteoclasts resorbed the bone efficiently. (haematologica.org)
  • This permits characterization of osteoclasts by their staining for high expression of tartrate resistant acid phosphatase (TRAP) and cathepsin K. Osteoclast rough endoplasmic reticulum is sparse, and the Golgi complex is extensive. (wikipedia.org)
  • The cultured cells subjected to tartrate-resistant acid phosphatase (TRAP) staining, and expressions of osteoclast specific TRAP mRNA, CK mRNA, and CR mRNA were detected by RT-PCR. (shsmu.edu.cn)
  • Tartrate-resistant acid phosphatase (TRAP) and the osteoclast/immune cell dichotomy. (medlineplus.gov)
  • also known as OPGL, TRANCE, ODF and TNFSF11) and its receptor RANK (TNFRSF11A) are key regulators of bone remodeling, and they are essential for the development and activation of osteoclasts [1]. (thermofisher.com)
  • However, excessive activation of osteoclasts is responsible for many bone diseases such as osteoporosis, Paget disease, and tumor bone metastasis. (osteoporosis-studies.com)
  • Regulation of bone remodeling occurs through multiple mechanisms that ultimately converge on the interaction of osteoclasts or their precursors with osteoblasts and bone marrow stromal cells. (thermofisher.com)
  • Members of all three MAPK (Mitogen Activated Protein kinase) families, ERK (Extracellular signal Regulated Kinase), JNK, and p38, are activated by RANK in osteoclasts or osteoclast precursors [4]. (thermofisher.com)
  • Transplantation studies have suggested that peripheral blood mononuclear cells contain precursors for osteoclasts. (jci.org)
  • Three theories were dominant: from 1949 to 1970 the connective tissue origin was popular, which stated that osteoclasts and osteoblasts are of the same lineage, and osteoblasts fuse together to form osteoclasts. (wikipedia.org)
  • Thus we tested the capacity of peripheral blood monocytes to form osteoclasts in long-term culture. (jci.org)
  • Osteoclasts are specialized cells of the hematopoietic lineage that are responsible for bone resorption and play a critical role in musculoskeletal disease. (jci.org)
  • 1 - 4 ] The hematopoietic origin of osteoclasts has been well established as demonstrated in several osteopetrotic mouse models. (e-jbm.org)
  • 6 ] T-cell immune regulator 1 mutation in osteosclerotic (oc/oc) mice results in functionally impaired osteoclasts and increased bone mass, reversed by the transplantation of hematopoietic stem cells (HSCs). (e-jbm.org)
  • however, its role in osteoclasts in vivo has yet to be investigated. (jci.org)
  • A growing body of work provides evidence of the developmental origin and lifespan of murine osteoclasts, particularly in vivo . (e-jbm.org)
  • When osteoclast-inducing cytokines are used to convert macrophages to osteoclasts, very large cells that may reach 100 µm in diameter occur. (wikipedia.org)
  • These may have dozens of nuclei, and typically express major osteoclast proteins but have significant differences from cells in living bone because of the not-natural substrate. (wikipedia.org)
  • Osteoclast-like cells form in long-term human bone marrow but not in peripheral blood cultures. (jci.org)
  • We have reported previously that mononuclear cells from feline, baboon, and human marrow form osteoclast-like cells in long term cultures. (jci.org)
  • Thus, these bone marrow-derived multinucleated cells fulfill the functional criteria for osteoclasts. (jci.org)
  • These results indicate that osteoclasts or cells closely related to osteoclasts form in long-term human bone marrow cultures. (jci.org)
  • In contrast, few mononuclear cells in the peripheral blood appear capable of forming osteoclasts under the culture conditions used in these experiments. (jci.org)
  • Osteoclasts are multinucleated bone-resorbing cells and a key player in bone remodeling for health and disease. (e-jbm.org)
  • Osteoclasts are multinucleated bone-resorbing cells that play an integral role in physiological bone remodeling, repair in bone injury, and pathological bone resorption commonly associated with osteoporosis or inflammatory conditions such as rheumatoid arthritis (RA) and osteolysis. (e-jbm.org)
  • 5 - 7 ] Osteopetrosis which is mediated by defective osteoclasts in microphtalmic (mi/mi) mice is rescued by the transplantation of bone marrow (BM) or spleen mononucleated cells from normal mice, and functional osteoclasts are observed within 2 to 3 weeks after transplantation. (e-jbm.org)
  • Osteoclasts share several cellular and molecular properties of myeloid cells. (e-jbm.org)
  • 12 ] Myeloid cells comprise different cell types such as osteoclasts, granulocytes, monocytes, macrophages, and dendritic cells (DCs), which are found in various tissues in homeostatic conditions and circulate through the blood and lymphatic system. (e-jbm.org)
  • 13 - 15 ] Circulating peripheral monocytes give rise to a variety of tissue-resident macrophages throughout the body as well as to specialized cells such as DCs and osteoclasts. (e-jbm.org)
  • osteoclasts are the sole bone-resorbing cells that reside on bone and secrete acids and proteases to dissolve the bone matrix. (e-jbm.org)
  • Bisphosphonates, or drugs that slow down bone cells called osteoclasts, can be used to alleviate pain and high calcium levels that result from bone metastasis. (healthline.com)
  • Since osteoclasts can become overactive in advanced prostate cancer that has spread to the bones, these help slow the growth of cancer cells while also preventing fractures and strengthening the bones. (healthline.com)
  • Results Cells began to merge on the sixth day after culture with Ti-6Al-4V particles, and multinucleated giant cells emerged on the ninth day, with positive TRAP staining and expressions of osteoclast specific TRAP mRNA, CK mRNA, and CR mRNA. (shsmu.edu.cn)
  • Meanwhile, gastrodin prevented osteoclast maturation and migration by inhibiting the gene expression of dendrocyte expressed seven transmembrane protein (DC-STAMP) , an osteoclastic-specific gene that controls cells fusion and movement. (osteoporosis-studies.com)
  • Osteoclast cultures were generated from peripheral blood mononuclear cells of three patients using the peripheral blood mononuclear cell isolation. (bvsalud.org)
  • The TRAP enzyme primarily regulates the activity of a protein called osteopontin, which is produced in bone cells called osteoclasts and in immune cells. (medlineplus.gov)
  • Two versions (isoforms) of the TRAP enzyme are produced: TRAP5a is found primarily in immune cells and TRAP5b is found primarily in bone cells called osteoclasts. (medlineplus.gov)
  • Osteoclasts are specialized cells that break down and remove (resorb) bone tissue that is no longer needed. (medlineplus.gov)
  • As a result, osteopontin is abnormally active, prolonging bone breakdown by osteoclasts and triggering abnormal inflammation and immune responses by immune cells. (medlineplus.gov)
  • 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)
  • A viral etiology, such as measles, has been proposed because nuclear inclusions in diseased osteoclasts that are similar to those seen in paramyxovirus-infected cells have been seen on electron microscopy. (msdmanuals.com)
  • Since the discovery of osteoclasts in 1873, the structure and function of osteoclasts and the molecular and cellular mechanisms of osteoclastogenesis have been extensively studied. (e-jbm.org)
  • The effects of estrogen on cytokine modulation of osteoclastogenesis is examined as well as direct actions of estrogen on osteoclast activity and programmed cell death. (elsevierpure.com)
  • Effects of zoledronic acid and geranylgeraniol on angiogenic gene expression in primary human osteoclasts. (bvsalud.org)
  • Replacement of the mevalonate pathway using geranylgeraniol (GGOH) was studied to determine the effects of ZA on angiogenic gene expression in primary human osteoclasts . (bvsalud.org)
  • In this study, we investigated the effects of gastrodin on receptor activator NF-κB ligand (RANKL)-activated osteoclasts formation and bone resorption. (osteoporosis-studies.com)
  • We report that murine osteoclast formation in culture is inhibited by both lovastatin, an inhibitor of hydroxymethylglutaryl CoA reductase, and alendronate. (ox.ac.uk)
  • Ca 3 ZrSi 2 O 9 ceramics supported the fusion of monocytes to form functional osteoclasts with their characteristic features of f-actin ring structures and the expression of α v β 3 integrin consistent with functional activity. (edu.au)
  • 16 , 17 ] In addition to monocytes/macrophages, DCs also serve as a source of osteoclasts. (e-jbm.org)
  • The size of the multinucleated assembled osteoclast allows it to focus the ion transport, protein secretory and vesicular transport capabilities of many macrophages on a localized area of bone. (wikipedia.org)
  • This study suggests that, in osteoclasts, geranylgeranyl diphosphate, the substrate for prenylation of most GTP binding proteins, is likely to be the crucial intermediate affected by these bisphosphonates. (ox.ac.uk)
  • Similar to bisphosphonates, denosumab can also be used to block osteoclasts and help prevent fractures. (healthline.com)
  • The activity of osteoclasts is controlled by hormones and cytokines. (wikipedia.org)
  • Estradiol is a type of estrogen that assists osteoblasts, suppresses cytokines, and inhibits osteoclast activity. (bvsalud.org)
  • XIAP (Xenopus Inhibitor of Apoptosis) and cIAP are downstream targets of NF-kappaB in osteoclast survival pathway. (thermofisher.com)
  • Another transcription factor MITF (Microphthalmia-Associated Transcription Factor) is a target of p38 in the RANK-signaling pathway in osteoclasts [6]. (thermofisher.com)
  • Together, these findings support the hypothesis that alendronate, acting directly on osteoclasts, inhibits a rate-limiting step in the cholesterol biosynthesis pathway, essential for osteoclast function. (ox.ac.uk)
  • These results show that the systemic IL-6 effector pathway mediates bone deterioration induced by repetitive inhalant ODE exposures through an effect on osteoclasts, but a positive role for IL-6 in the airway was not demonstrated. (cdc.gov)
  • Several other mutations associated with Paget disease have been identified, many affecting the RANK (receptor activator of nuclear factor kappa-B) signaling pathway that is critical for osteoclast generation and activity. (msdmanuals.com)
  • Interestingly, Oc-JAK2-KO mice had reduced osteoclast-specific expression of IGF1, suggesting a role for osteoclast-derived IGF1 in determination of body size. (jci.org)
  • However, PTH stimulates the osteoblasts to secrete the cytokine called osteoclast-stimulating factor, which is a potent stimulator of the osteoclastic activity. (wikipedia.org)
  • The osteoclasts pump hydrogen ions into subosteoclastic compartment and thus create an acidic microenvironment, which increases solubility of bone mineral, resulting in the release and re-entry of bone minerals into the cytoplasm of osteoclasts to be delivered to nearby capillaries. (wikipedia.org)
  • Effect: increases osteoclast activity to break down bone and release calcium into bloodstream. (genial.ly)
  • Cathepsin K, Carbonic Anhydrase II, Matrix metalloproteinase-9, receptor activator of NF-κB and Calcitonin Receptor, consistent with the formation of functional osteoclasts. (edu.au)
  • Src and PI3K function at the point where RANK and adhesion signals converge, transmitting the signals for proper actin cytoskeletal organization that facilitates resorption activity of osteoclasts [7]. (thermofisher.com)
  • Furthermore, rabbit osteoclast formation and activity also are inhibited by lovastatin and alendronate. (ox.ac.uk)
  • 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)
  • Although a viral cause remains controversial, it is hypothesized that in genetically predisposed patients an as yet unidentified virus triggers abnormal osteoclast activity. (msdmanuals.com)
  • This extensively folded or ruffled border facilitates bone removal by dramatically increasing the cell surface for secretion and uptake of the resorption compartment contents and is a morphologic characteristic of an osteoclast that is actively resorbing bone. (wikipedia.org)
  • Because of their phagocytic properties, osteoclasts are considered to be a component of the mononuclear phagocyte system (MPS). (wikipedia.org)
  • Other intracellular adaptor proteins that interact with TRAF proteins and regulate the function of TRAF in osteoclasts are TAK1 (TGF-Beta Activated Kinase) and NIK (NF-KappaB-Inducing Kinase). (thermofisher.com)
  • Src act as a mediator of the RANK to PI3K (Phosphatidylinositol-3 Kinase)/Akt1 signal in osteoclasts. (thermofisher.com)
  • Among the many molecules downstream of Src, PYK2 (Protein Tyrosine Kinase-2) and c-Cbl are implicated in osteoclast adhesion signaling and bone resorption function. (thermofisher.com)
  • Signaling studies show that lovastatin and alendronate activate in purified osteoclasts a 34-kDa kinase. (ox.ac.uk)
  • An osteoclast (from Ancient Greek ὀστέον (osteon) 'bone', and κλαστός (clastos) 'broken') is a type of bone cell that breaks down bone tissue. (wikipedia.org)
  • An osteoclast is a large multinucleated cell and human osteoclasts on bone typically have four nuclei and are 150-200 µm in diameter. (wikipedia.org)
  • Excessively active osteoclasts are often large and contain many nuclei. (msdmanuals.com)
  • The degradation products are phagocytosed by osteoclasts at the ruffled border. (wikipedia.org)
  • Among the TRAF proteins, TRAF6 is critical for RANK signaling in osteoclasts. (thermofisher.com)
  • This inhibition is prevented by exogenous geranylgeraniol, probably required for prenylation of GTP binding proteins that control cytoskeletal reorganization, vesicular fusion, and apoptosis, processes involved in osteoclast activation and survival. (ox.ac.uk)
  • These evidences indicate osteoclasts as direct target of mechanical forces and further address future studies to the understanding of the cellular and molecular mechanisms of osteoclast behavior in microgravity. (uniba.it)
  • Nelson H, Gravallese E, Charles J, Jacome-Galarza C. Cellular Origin and Functions of Osteoclasts in Inflammatory Arthritis [abstract]. (acrabstracts.org)
  • The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption. (wikipedia.org)
  • In the mouse model, mature osteoclasts, which are essential for tooth eruption, are lacking. (medscape.com)
  • Bone remodeling results from the coordinate action of bone resorption by osteoclasts and the formation of new bone by osteoblasts. (thermofisher.com)
  • Additionally, the association of the actin-binding protein gelsolin with PI3K is important in actin filament formation in osteoclasts. (thermofisher.com)
  • Agents that could inhibit osteoclast formation or function are regarded as promising alternatives to treat osteoclast-related diseases. (osteoporosis-studies.com)
  • however, this was not associated with significant changes in bone density, microarchitecture, or strength, indicating that the observed phenotype was not due to alterations in canonical osteoclast function. (jci.org)
  • Together, our data show a potentially novel role for Oc-JAK2 and IGF1 in the determination of body size, which is independent of osteoclast resorptive function. (jci.org)
  • The longer the duration of menopause, the more estradiol function decreases, which causes osteoclasts to become active in bone resorption [3]. (bvsalud.org)
  • At a site of active bone resorption, the osteoclast forms a specialized cell membrane, the "ruffled border", that opposes the surface of the bone tissue. (wikipedia.org)
  • Giant osteoclasts in patients und. (unige.ch)
  • 8 - 11 ] These studies support that osteoclasts originate from a myeloid cell origin. (e-jbm.org)
  • During bone remodeling, osteopontin is turned on (activated), allowing osteoclasts to attach (bind) to bones. (medlineplus.gov)
  • Resorption of bone matrix by the osteoclasts involves two steps: (1) dissolution of inorganic components (minerals), and (2) digestion of organic component of the bone matrix. (wikipedia.org)