Involvement of αvβ3 integrins in osteoclast function

Integrins are heterodimeric adhesion receptors that mediate cell–matrix interaction. Osteoclast exhibits high expression of the αvβ3 integrin, which binds to a variety of extracellular matrix proteins including vitronectin, osteopontin, and bone sialoprotein. Arg-Gly-Asp (RGD)-containing peptides, RGD-mimetics, and blocking antibodies to αvβ3 integrin were shown to inhibit bone resorption in vitro and in vivo, suggesting that this integrin may play an important role in regulating osteoclast function. Several lines of evidence have demonstrated that a number of signaling molecules are involved in the αvβ3 integrin-dependent signaling pathway, including c-Src, Pyk2, c-Cbl, and p130Cas. In this article, we review the history of “αvβ3 integrin and osteoclasts” and discuss the involvement of αvβ3 integrins in osteoclast function at tissue, cellular, and molecular levels. A better understanding of the role of αvβ3 integrin in osteoclastic bone resorption would provide opportunities for developing new therapeutics to treat human bone diseases, including rheumatoid arthritis, osteoporosis, and periodontal disease.