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Updated: Jul 19, 2026
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Published on: February 2, 2024
Alpha9beta1: a novel osteoclast integrin that regulates osteoclast formation and function.
Hongwei Rao1, Ganwei Lu, Hiroshi Kajiya
1Medicine-Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Summary
A novel integrin, alpha(9)beta(1), was identified on osteoclasts (OCLs). Blocking this integrin impaired OCL formation and bone resorption, revealing its critical role in bone remodeling.
Area of Science:
- Cell Biology
- Integrin Signaling
- Bone Biology
Background:
- Integrins are crucial for osteoclast (OCL) formation and function.
- Mature OCLs primarily express alpha(v)beta(3) integrin, involved in bone resorption.
- ADAM8 was identified as a novel stimulator of OCL differentiation, with its disintegrin domain mediating effects.
Purpose of the Study:
- To identify the specific integrin that binds to the disintegrin domain of ADAM8.
- To characterize the role of this integrin in OCL formation and activity.
Main Methods:
- Binding assays using Chinese hamster ovary (CHO) cells expressing various integrin subunits.
- Analysis of alpha(9)beta(1) integrin expression in mouse and human OCLs via Western blot, immunocytochemistry, and RT-PCR.
- Inhibition studies using a monoclonal antibody against alpha(9) and assessment of OCLs from alpha(9) knockout mice.
Main Results:
- Alpha(9)beta(1) integrin was found to be expressed on OCLs and their precursors.
- Anti-alpha(9) antibody significantly inhibited human OCL formation.
- OCLs from alpha(9) knockout mice exhibited defective actin ring reorganization and reduced bone resorption capacity.
- Histomorphometry and microCT analysis of alpha(9) knockout mice revealed increased trabecular bone volume.
Conclusions:
- Alpha(9)beta(1) integrin plays a previously unrecognized role in osteoclast formation and function.
- This integrin is essential for proper OCL activity and bone remodeling.
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