c-Fms and the αvβ3 integrin collaborate during osteoclast differentiation

Faccio, Roberta; Takeshita, Satoshi; Zallone, Alberta; Ross, F. Patrick; Teitelbaum, Steven L.

doi:10.1172/jci16924

Cited by 104 publications

(132 citation statements)

References 48 publications

(37 reference statements)

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“…The classical pathway for osteoclast differentiation and activation involves interaction of osteoblastic M-CSF and RANKL with the cognate receptors c-fms and RANK on osteoclast precursors [45][46][47][48][49]. Changes in production of M-CSF and RANKL, as well as proinflammatory cytokines (IL-1, IL-6, TNF-a) and PGE2, result from particle uptake and/or metal ion effects on osteoblasts and macrophages, and also impact osteoclast activity [24,28,29,50,51].…”

Section: Discussionmentioning

confidence: 99%

Effects of soluble cobalt and cobalt incorporated into calcium phosphate layers on osteoclast differentiation and activation

2009

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Section: Discussionmentioning

confidence: 99%

Effects of soluble cobalt and cobalt incorporated into calcium phosphate layers on osteoclast differentiation and activation

2009

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“…Ligation of α v β 3 either by ligand binding or by antibody-mediated clustering increases Pyk2 tyrosine phosphorylation at the autoactivation site Tyr 402 [56,62,87]. This is dependent upon the presence of the β 2 as well as β 3 integrins [88] and is mediated, in part, by Src [56,62,87]. In support of this, tyrosine phosphorylation and kinase activity of Pyk2 are reduced in Src −/− osteoclasts [62] which do not form actin rings and fail to resorb bone [74].…”

Section: Pyk2 Is Activated Downstream Of Integrins and Promotes Bone mentioning

confidence: 99%

“…However, Cbl also acts as E3 ubiquitin ligase and simultaneously targets activated c-Fms for degradation, thereby attenuating signaling and macrophage proliferation [194]. High doses of M-CSF have also been shown to rescue signaling, spreading and differentiation in β 3 knockout osteoclasts but do not rescue the resorptive activity of these osteoclasts [88], indicating that c-Fms alone is insufficient to support bone resorption by osteoclasts.…”

Section: Signaling By C-fms and Rankmentioning

confidence: 99%

Molecular regulation of osteoclast activity

Bruzzaniti

Baron

2006

Rev Endocr Metab Disord

157

119

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Osteoclasts are multinucleated cells derived from hematopoietic precursors that are primarily responsible for the degradation of mineralized bone during bone development, homeostasis and repair. In various skeletal disorders such as osteoporosis, hypercalcemia of malignancy, tumor metastases and Paget's disease, bone resorption by osteoclasts exceeds bone formation by osteoblasts leading to decreased bone mass, skeletal fragility and bone fracture. The overall rate of osteoclastic bone resorption is regulated either at the level of differentiation of osteoclasts from their monocytic/macrophage precursor pool or through the regulation of key functional proteins whose specific activities in the mature osteoclast control its attachment, migration and resorption. Thus, reducing osteoclast numbers and/or decreasing the bone resorbing activity of osteoclasts are two common therapeutic approaches for the treatment of hyper-resorptive skeletal diseases. In this review, several of the key functional players involved in the regulation of osteoclast activity will be discussed.

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“…M-CSF induces RANK expression on the cell surface of pre-osteoclasts rendering them responsive to the osteoclastogenic effects of RANKL [34]. M-CSF mediates its osteoclastogenic effects by binding to c-fms, a tyrosine kinase receptor that induces osteoclast differentiation via activation of ERK1/2 and PI3-K/AKT [35].…”

Section: Cytokines and Chemokines Involved In Osteoclastogenesismentioning

confidence: 99%

Osteoclastogenesis and arthritis

et al. 2010

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There is emerging interest for osteoclasts as key players in the erosive and inflammatory events leading to joint destruction in chronic arthritis. In fact, chronic inflammatory joint diseases such as psoriatic arthritis and rheumatoid arthritis are often characterized by destruction of juxta-articular bone and erosions due to the elevated activity of osteoclasts, which are involved in bone resorption. The main step in inflammatory bone erosion is an imbalance between bone resorption and bone formation: osteoclast formation is enhanced by proinflammatory cytokines such as TNF-α, IL-1β, and IL-17 and is not balanced by increased activity of bone-forming osteoblasts. T-cells, stromal cells, and synoviocytes enhance osteoclast formation via expression of RANKL and, under pathologic conditions, of proinflammatory cytokines. In rheumatoid arthritis, accumulation of osteoclasts in synovial tissues and their activation associated with osteoclastogenic cytokines and chemokines at cartilage erosion sites suggest that they could be usefully selected as therapeutic target. In particular, in consideration of the primary role of RANKL and TNF-α in osteoclastogenesis, the control of the production of RANKL and the inhibition of TNF-α represent important strategies for reducing bone damage in this disease.

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c-Fms and the αvβ3 integrin collaborate during osteoclast differentiation

Cited by 104 publications

References 48 publications

Effects of soluble cobalt and cobalt incorporated into calcium phosphate layers on osteoclast differentiation and activation

Effects of soluble cobalt and cobalt incorporated into calcium phosphate layers on osteoclast differentiation and activation

Molecular regulation of osteoclast activity

Osteoclastogenesis and arthritis

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