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Updated: May 21, 2026
07:51
Effect of Anti-c-fms Antibody on Osteoclast Formation and Proliferation of Osteoclast Precursor In Vitro
Published on: March 18, 2019
Role of intercellular adhesion molecule-2 in osteoclastogenesis
Xianglan Li1, Masako Akiyama, Ken-ichi Nakahama
1Department of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8549, Japan.
Summary
Intercellular adhesion molecule-2 (ICAM-2) binding to Mac-1 is crucial for osteoclast formation. Blocking ICAM-2 inhibits osteoclastogenesis induced by RANKL or TNFα, highlighting its role in bone resorption.
Area of Science:
- Cell Biology
- Immunology
- Bone Biology
Background:
- Osteoclasts are multinucleated bone-resorbing cells crucial for bone remodeling.
- Osteoclast differentiation requires fusion of monocyte/macrophage precursors.
- Previous research identified Mac-1 (CD11b/CD18) as important for osteoclastogenesis, but its counter-receptor remained unknown.
Purpose of the Study:
- To identify the counter-receptor for Mac-1 involved in osteoclastogenesis.
- To elucidate the role of ICAM-1 and ICAM-2 in osteoclast formation.
- To investigate the signaling pathways (RANKL and TNFα) involved in Mac-1 mediated osteoclastogenesis.
Main Methods:
- Flow cytometry to analyze cell surface marker expression on osteoclast precursors.
- Quantitative RT-PCR to assess ICAM-1 and ICAM-2 expression levels.
- Neutralizing antibody experiments to block ICAM-2 and CD11b functions during osteoclastogenesis induced by RANKL and TNFα.
- Immunocytochemical staining to visualize ICAM-2 and Mac-1 colocalization.
Main Results:
- Bone marrow-derived mononuclear cells expressed both ICAM-1 and ICAM-2, with higher ICAM-2 levels.
- Anti-ICAM-2 antibody significantly inhibited RANKL-induced osteoclastogenesis, an effect enhanced by anti-CD11b antibody.
- Anti-ICAM-2 antibody also inhibited TNFα-induced osteoclastogenesis, independent of lymphocytes.
- ICAM-2 and Mac-1 colocalized during osteoclastogenesis, with Mac-1 expression diminishing in mature osteoclasts.
Conclusions:
- ICAM-2 acts as the functional counter-receptor for Mac-1 during osteoclastogenesis.
- ICAM-2/Mac-1 interaction plays a critical role in osteoclast formation induced by both RANKL and TNFα.
- Targeting the ICAM-2/Mac-1 pathway may offer therapeutic strategies for bone-resorbing diseases.
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