• In contrast, TNF often acts on cell types other than osteoclasts, or synergically with RANKL to indirectly promote osteoclastogenesis and bone resorption. (frontiersin.org)
  • Osteoclast differentiation is induced by the master osteoclastogenic factor, RANKL, which acts in concert with M-CSF and ITAM-mediated co-stimulatory signaling. (frontiersin.org)
  • Therefore, inhibition of RANKL-induced osteoclastogenesis and osteoclast-induced bone resorption is an important approach in controlling pathophysiology of these skeletal diseases. (hindawi.com)
  • We found that, of seven type I, II, and III saikosaponins isolated from Bupleurum falcatum , saikosaponins A and D, type I saikosaponins with an allyl oxide linkage between position 13 and 28 and two carbohydrate chains that are directly attached to the hydroxyl groups in position 3, exhibited the most potent inhibition on RANKL-induced osteoclast formation at noncytotoxic concentrations. (hindawi.com)
  • Saikosaponins A and D inhibited the formation of resorptive pits by reducing the secreted levels of matrix metalloproteinase- (MMP-) 2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. (hindawi.com)
  • We also found that rapid application of the osteoclast-activation factor RANKL converted many N osteoclasts to R, suggesting a novel point of action in RANKL-mediated control of mature osteoclast function. (jci.org)
  • Furthermore, we showed that Th17 cells, a subset of RANKL-expressing CD4 + T cells, could induce rapid N-to-R conversion of mature osteoclasts via cell-cell contact. (jci.org)
  • These findings provide new insights into the activities of mature osteoclasts in situ and identify actions of RANKL-expressing Th17 cells in inflammatory bone destruction. (jci.org)
  • Prolia binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption. (druglib.com)
  • Prolia prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. (druglib.com)
  • Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone. (druglib.com)
  • Binding stimulates osteoblasts to increase their expression of RANKL , which can bind to osteoclast precursors containing RANK, a receptor for RANKL. (bionity.com)
  • The binding of RANKL to RANK stimulates these precursors to fuse, forming new osteoclasts which ultimately enhances the resorption of bone. (bionity.com)
  • Expression of RANKL correlated with the number of osteoclasts (r = 0.592, p = 0.004). (bmj.com)
  • The increased number of osteoclasts and RANKL expression in samples with MRI bone oedema supports the hypothesis that bone erosion in RA occurs through activation of local bone resorption mechanisms within subchondral bone as well as through synovial invasion into bone. (bmj.com)
  • Non-Canonical (RANKL-Independent) Pathways of Osteoclast Differentiation and Their Role in Musculoskeletal Diseases. (ox.ac.uk)
  • in the canonical pathway of osteoclastogenesis, these cells fuse and differentiate to form specialised bone-resorbing osteoclasts in the presence of receptor activator for nuclear factor kappa B ligand (RANKL). (ox.ac.uk)
  • This review summarises the evidence for these RANKL substitutes in inducing osteoclast differentiation from tissue-derived and circulating mononuclear phagocytes. (ox.ac.uk)
  • Osteoclasts and odontoclasts are multinucleated cells derived from hematogenous bone marrow, from the monocyte/macrophage cell lineage, and are formed by the fusion of these cells under the action of colony stimulating factor 1 (CSF-1), macrophage colony stimulating factor (M-CSF), monocyte chemotactic protein-1 (MCP-1) and RANKL (receptor activator of nuclear factor kappa-B ligand), which also have a role in chemotaxis and cell differentiation [1]. (oatext.com)
  • The differentiation of the osteoclast precursor into a mature osteoclast requires RANKL binding to its receptor RANK (receptor activator of nuclear factor kappa-B). However, OPG binding to RANKL will block RANKL binding to RANK, which will result in inhibition of osteoclastogenesis (Figure 1) [3]. (oatext.com)
  • We show that H3 monomethylation at lysine 27 (H3K27me1) is essential for MMP-9-dependent H3NT proteolysis during RANKL-induced osteoclast differentiation. (biomedcentral.com)
  • The binding of RANKL to its cognate receptor RANK on pre-osteoclast cell membrane stimulates the expression of key determinants of osteoclast differentiation such as NF-κB, c-Fos, and NFATc1 at the early stage of the process [ 1 , 8 ]. (biomedcentral.com)
  • In turn, MM cells-derived RANKL causes the upregulation of its receptor, RANK, and Notch2 in pre-osteoclasts. (oncotarget.com)
  • Notch2 stimulates osteoclast differentiation by promoting autocrine RANKL signaling. (oncotarget.com)
  • His work was the first to show that the human osteoclast shares specific surface antigens with macrophages and that the mononuclear human osteoclast precursor circulates in the (CD14+) monocyte fraction. (wikipedia.org)
  • Mechanistically, ProCT inhibits the expression of key mediators involved in the recruitment of macrophages, representing osteoclast precursors. (nih.gov)
  • Many types of cells are involved in the progression of RA joint inflammation, among which the overactivation of M1 macrophages and osteoclasts has been thought to be an essential cause of joint inflammation and bone destruction. (elifesciences.org)
  • By pharmacological inhibition of GLI1, the proportion of proinflammatory macrophages and the number of osteoclasts were significantly reduced, and the joint inflammatory response and bone destruction in CIA mice were alleviated. (elifesciences.org)
  • This study presents an important finding on the role of GLI1 in macrophages and osteoclasts in the pathogenesis of inflammatory arthritis, and suggests a therapeutic potential of GLI1 targeting in rheumatoid arthritis. (elifesciences.org)
  • The tumors are typically composed of a small number of these cells and a high percentage of myeloid precursors (monocytes and macrophages) that have CSF-1 receptors (CSF-1R). (msdmanuals.com)
  • Previously, we reported that distinct murine osteoclast precursor subsets, such as early blasts (CD31hi Ly-6C−), myeloid blasts (CD31+ Ly-6C+), and monocytes (CD31− Ly-6Chi), respond differently to the osteoclastogenesis-inducing cytokines, macrophage colony-stimulating factor, and receptor activator for nuclear factor κB ligand. (vu.nl)
  • This study aims to investigate the effect of interleukin 1β on osteoclastogenesis derived from different mouse bone marrow precursors. (vu.nl)
  • Similar to E2, the complex I inhibitor Rotenone decreased osteoclastogenesis by promoting osteoclast progenitor apoptosis via Bak/Bax. (bvsalud.org)
  • Recent studies have uncovered key intrinsic mechanisms by which TNF acts on osteoclast precursors to restrain osteoclastogenesis, including the mechanisms mediated by RBP-J signaling, RBP-J and ITAM (Immunoreceptor tyrosine-based activation motif) crosstalk, RBP-J mediated regulatory network, NF- κ B p100, IRF8, and Def6. (frontiersin.org)
  • Based on these lines of evidence, we hypothesize that HMGB1-mediated suppression of ACdase in senescent osteoclast precursors leads to the increased levels of intracellular ceramides that actively signal and, in turn, promote osteoclastogenesis in periodontal lesions of the aging population. (nova.edu)
  • Here we present evidences that MM can efficiently drive osteoclastogenesis by contemporaneously activating Notch signaling on tumor cells and osteoclasts through the aberrant expression of Notch ligands belonging to the Jagged family. (oncotarget.com)
  • Such synergism between tumor cells and pre-osteoclasts in MM-induced osteoclastogenesis can be disrupted by silencing tumor-derived Jagged1 and 2. (oncotarget.com)
  • The CSF-1 stimulates the growth of these myeloid precursor cells. (msdmanuals.com)
  • Immunophenotypic differences between osteoclasts and macrophage polykaryons: immunohistological distinction and implications for osteoclast ontogeny and function. (wikipedia.org)
  • Osteoclasts are bone cells derived from monocyte/macrophage lineage and are exclusively responsible for bone resorption, which contributes to skeletal development, bone homeostasis, and remodeling. (frontiersin.org)
  • Osteoclasts are bone resorbing, multinucleate cells that differentiate from mononuclear macrophage/monocyte-lineage hematopoietic precursor cells. (jci.org)
  • The decreased expression and inhibition of nuclear transfer of GLI1 downregulated macrophage M1 polarization and osteoclast activation, the effect of which was achieved by modulation of DNA methyltransferases (DNMTs) via transcriptional regulation and protein interactions. (elifesciences.org)
  • This study clarified the mechanism of GLI1 in macrophage phenotypic changes and activation of osteoclasts, suggesting potential applications of GLI1 inhibitors in the clinical treatment of RA. (elifesciences.org)
  • Here, we identified Calca, encoding the sepsis biomarker procalcitonin (ProCT), as a novel target gene of PTH in murine osteoblasts that inhibits osteoclast formation. (nih.gov)
  • One of the central objectives of this project was the development and characterization of a 3D mineralized tissue model system in which the effects of mechanical load (e.g., compression loading, tension, vibration, etc.) on the cellular responses of osteoblasts and osteoclasts could be investigated. (techbriefs.com)
  • Until recently many studies of bone remodeling at the cellular level have focused on the behavior of mature osteoblasts and osteoclasts, and their respective precursor cells, with the role of osteocytes and bone lining cells left largely unexplored. (ebi.ac.uk)
  • We found that interleukin 1β stimulated multinucleation and bone resorption of osteoclasts derived from the 3 precursors at different rates. (vu.nl)
  • 20 nuclei) and highest level of bone resorption (16.3%) was by myeloid blast-derived osteoclasts. (vu.nl)
  • Our results indicate that the different bone marrow osteoclast precursors are differently stimulated by interleukin 1β with respect to proliferation, multinucleation, life span, and bone resorption. (vu.nl)
  • With TJ Chambers he developed the osteoclast lacunar bone resorption assay system. (wikipedia.org)
  • 1984). Resorption of bone by isolated rabbit osteoclasts. (wikipedia.org)
  • Under inflammatory conditions, abnormal osteoclast differentiation and function often results in excessive bone resorption, which is a common characteristic of many diseases, such as osteoporosis, rheumatoid arthritis (RA), psoriatic arthritis and periodontitis ( 1 - 5 ). (frontiersin.org)
  • Current treatments for excessive bone resorption utilize RANK receptor blockers or neutralizing antibodies, which are able to inhibit osteoclast formation. (frontiersin.org)
  • Given the rate of transition from static to motile behavior of the osteoclasts, these areas are likely to be those undergoing resorption by previously static cells shortly before obtaining the image and characterizing the osteoclasts at motile. (jci.org)
  • During iPTH treatment, mice lacking ProCT develop increased bone resorption with excessive osteoclast formation in both the long bones and axial skeleton. (nih.gov)
  • [2] Bone resorption is the normal destruction of bone by osteoclasts , which are indirectly stimulated by PTH. (bionity.com)
  • The possible mechanisms involved in osteoclasts recruitment from external granuloma and various dentin resorption patterns in internal root resorption will be discussed based on a case in which the upper lateral incisor with a history of pulp necrosis treated endodontically, developed an internal root resorption in association with external granuloma. (oatext.com)
  • Bone resorption is initiated by osteoclasts and resorption of hard dental structures by odontoclasts. (oatext.com)
  • Osteoclasts recruitment and activation, and angiogenesis in maxillary alveolar processes in internal root resorption associated with external granuloma. (oatext.com)
  • Once migrated to the bone marrow, MM cells unbalance bone formation and resorption via the recruitment and maturation of osteoclast precursors. (oncotarget.com)
  • It is unknown, however, how these cell types respond to the osteoclast-stimulating inflammatory cytokine interleukin 1β. (vu.nl)
  • 1996) The human mononuclear osteoclast precursor circulates in the monocyte fraction. (wikipedia.org)
  • Monocytes needed the longest time (95 h) for the generation of such large osteoclasts, but these cells had a longer life span (50 h). (vu.nl)
  • Lymphocytic aggregates containing CD45RO+ T cells and B cells within bone marrow have been identified in subchondral bone in RA, 8 and a recent immunohistochemical study reported an association between bone marrow inflammation and osteoclasts in RA subchondral bone. (bmj.com)
  • Here, we visualized fluorescently labeled mature osteoclasts in intact mouse bone tissues using intravital multiphoton microscopy. (jci.org)
  • Mineralized 3D bone constructs fluorescently stained to track osteoclast precursor cells, revealed as white portions in the image. (techbriefs.com)
  • His work on hip and knee implants focused on the importance of biomaterial wear particles on promoting osteoclast formation, osteolysis and implant loosening. (wikipedia.org)
  • Estrogens protect against bone loss by decreasing osteoclast number through direct actions on cells of the myeloid lineage. (bvsalud.org)
  • In Specific Aim 2, we will elucidate the molecular mechanisms underlying ceramide-mediated fusion of senescent osteoclast precursors in vitro through a cathepsin B-induced Myh9 degradation pathway. (nova.edu)
  • We report that 17ß- estradiol (E2) decreased osteoclast number by promoting the apoptosis of early osteoclast progenitors, but not mature osteoclasts . (bvsalud.org)
  • Instead, using microarray analysis we have elucidated that ERα-mediated estrogen signaling in osteoclast progenitors decreases " oxidative phosphorylation " and the expression of mitochondria complex I genes . (bvsalud.org)
  • These findings demonstrate that estrogens decrease osteoclast number by attenuating respiration , and thereby, promoting mitochondrial apoptotic death of early osteoclast progenitors. (bvsalud.org)
  • Interleukin 1β particularly accelerated proliferation of early blasts and the most small osteoclasts (3-5 nuclei) formed on plastic. (vu.nl)
  • The exact cause of GCTs is not fully understood, but they are thought to be related to abnormal proliferation and differentiation of osteoclast precursors. (medicinenet.com)
  • The H + secretion index was defined as the ratio of the number of osteoclasts overlapping with green fluorescent acid pH signals divided by the total number of osteoclasts of the indicated type that were imaged ( n = 3, from 3 independent experiments). (jci.org)
  • Their distinct biosynthetic activity includes an endoperoxidase synthase reaction that oxygenates and cyclizes polyunsaturated fatty acid precursors (eg, arachidonic acid) to form prostaglandin G 2 (PGG2), and a peroxidase reaction that converts PGG2 to prostaglandin H 2 (PGH2), as shown below. (medscape.com)
  • These cells are also tartrate resistant and non-specific esterase negative, and are believed to be precursors to osteoclasts and other acid phosphatase positive cells resorbing bone on the trabecular surface. (bmj.com)
  • By using RNAi and small molecule inhibitor approaches, we also confirmed that G9a is the major methyltransferase to catalyze H3K27me1 for MMP-9-dependent H3NT proteolysis and trigger the expression of osteoclast-specific genes. (biomedcentral.com)
  • Mature osteoclasts expressing TRAP-tdTomato signals ( A ), green fluorescent signals from high H + concentration ( B ), and merged images ( C ). Green fluorescent signals from the H + probes overlapped with static (low CDI, arrowheads) but not moving (high CDI, asterisk) osteoclasts, suggesting that former cells are secreting protons actively and resorbing bone tissues when observed in vivo. (jci.org)
  • When exploring the role of protein arginine methyltransferase 5 (PRMT5) in osteoclasts, we serendipitously developed a mouse model in which PSCs are specifically abrogated. (nature.com)
  • Long bones are formed from a cartilage model precursor by endochondral ossification (see the image below) and can range in size from a phalanx to a femur. (medscape.com)
  • Endochondral ossification of long bones through cartilage precursor. (medscape.com)
  • Finally, MM cells through Jagged ligands expression can also activate Notch signaling in pre-osteoclast by direct contact. (oncotarget.com)
  • 36: 945 - 954 PMID 16153456 Taylor R, Knowles H, Kashima T, Gibbons CLMH, Whitewell D, Athanasou NA, (2011) Osteoclast formation and function in pigmented villonodular synovitis. (wikipedia.org)
  • Giant cell tumors (GCTs) arise from cells called osteoclast precursors. (medicinenet.com)
  • Effects on osteoclast and osteoblast development and function. (nih.gov)
  • Another large gap in our understanding of osteoclastogenic transcription program is the identification of chromatin factors that have the potential to link specific aspects of chromatin function to osteoclast differentiation processes. (biomedcentral.com)
  • Under healthy physiological conditions, activities of osteoclasts and osteoblasts are tightly controlled by both systemic and local factors, maintaining bone mineral density and bone microarchitecture. (hindawi.com)
  • The density of osteoclasts was higher in those samples with MRI bone oedema than those without MRI bone oedema (p = 0.01). (bmj.com)
  • Human primary osteoblast/osteoclast 3D construct development following 21 days of culture (~4 mm diameter spheroids). (techbriefs.com)
  • In addition, as is characteristic to native periosteum, osteoclast precursor cells were imaged and proven to naturally arrange as an outer layer of the mineralized bone tissue construct. (techbriefs.com)
  • 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)