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Updated: May 5, 2026
07:51
Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro
Published on: March 18, 2019
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c-Fms and the alphavbeta3 integrin collaborate during osteoclast differentiation
Roberta Faccio1, Sunao Takeshita, Alberta Zallone
1Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
The Journal of Clinical Investigation
|March 6, 2003
Summary
Beta(3) integrin-null osteoclasts show impaired differentiation in vitro but increased numbers in vivo. Additional M-CSF rescues osteoclastogenesis by restoring ERK/c-Fos signaling via c-Fms tyrosine 697.
Area of Science:
- Cell Biology
- Integrin Signaling
- Bone Biology
Background:
- Beta(3) integrin-null osteoclasts exhibit paradoxical in vivo and in vitro behavior, with dysfunction but increased numbers in vivo, and reduced numbers due to differentiation arrest in vitro.
- This suggests differential cytokine regulation of osteoclastogenesis in different environments.
- Understanding the role of beta(3) integrin in osteoclast function is crucial for bone biology.
Purpose of the Study:
- To investigate the paradoxical regulation of beta(3) integrin-null osteoclastogenesis.
- To identify the specific components of the M-CSF receptor critical for osteoclastogenesis in beta(3) integrin-null cells.
- To elucidate the collaborative role of c-Fms and alpha(v)beta(3) in osteoclast differentiation and function.
Main Methods:
- In vitro osteoclast differentiation assays with varying M-CSF and RANKL concentrations.
- Analysis of extracellular signal-regulated kinases (ERK) activation and c-Fos expression.
- Retroviral transduction of osteoclast precursors with chimeric c-Fms constructs.
- Assessment of osteoclast matrix resorption capacity.
Main Results:
- Additional M-CSF, but not RANKL, rescued beta(3)(-/-) osteoclastogenesis in vitro, restoring ERK and c-Fos activation.
- Circulating and bone marrow M-CSF levels were elevated in beta(3)(-/-) mice, correlating with increased osteoclast numbers.
- Normalization of osteoclastogenesis and ERK activation in beta(3)(-/-) cells required c-Fms tyrosine 697.
- Overexpression of c-Fos normalized osteoclast numbers in vitro but not matrix resorption.
Conclusions:
- c-Fms and alpha(v)beta(3) integrin collaborate in osteoclastogenesis through shared ERK/c-Fos pathway activation.
- Beta(3) integrin is essential for osteoclast matrix degradation, independent of its role in differentiation signaling.
- Tyrosine 697 of c-Fms is a critical component for M-CSF-mediated osteoclastogenesis in beta(3) integrin-deficient cells.
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