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Integrins are a large family of heteromeric cell surface receptors composed of non-covalently bound and β subunits which interact with extracellular matrix molecules, serum constituents and the adhesion molecules of the immunoglobulin family. The extracellular domains of many integrins recognize the RGD (Arg-Gly-Asp) tripeptide found in several extracellular macromolecules such as fibronectin, vitronectin, fibrinogen and osteopontin. The vitronectin receptor, _vβ₃ integrin, is highly expressed in osteoclasts, the bone resorbing cells, and binds many of these RGD containing proteins including osteopontin, which is abundant in bone. Antibodies to _vβ₃, RGD peptides and RGD containing proteins such as echistatin, and kistrin were shown to inhibit bone resorption in vitro and in vivo. The identity of the _vβ₃ natural ligand and its mode of action in bone are so far not known. In addition to the very high levels of _vβ₃, mammalian osteoclasts also express ₂β₁, a collagen/laminin receptor and _vβ₁, another vitronectin receptor. Signaling events that follow substrate recognition by osteoclasts are not well understood. RGD containing peptides and proteins modulate [Ca²⁺] transients in osteoclasts and phosphatidylinositol 3-kinase and pp60^c-src are associated with _vβ₃ in these cells. _v and β₃ genes were shown to be regulated by the calciotropic hormone 1,25(OH)₂D₃ and by a number of cytokines known to be modulators of bone metabolism. In summary, elucidation of the interactions of osteoclast integrins with components of bone matrix, may lead to further understanding of the mechanism of bone resorption.

Journal of Endocrinology (1997) 154, S47–S56