Regulatory mechanism of osteoclast activation

Osteoclasts are multinucleated, terminally differentiated cells which play an essential role in bone resorption. Osteoclasts exhibit high expression of the alpha(v)beta(3) integrin, which binds to a variety of extracellular matrix proteins, including vitronectin, osteopontin and bone sialoprotein. RGD (Aug-Gly-Asp)-containing peptides, RGD-mimetics and blocking antibodies to alpha(v)beta(3) integrin were shown to inhibit bone resorption in vitro and in vivo, suggesting that this integrin plays an important role in regulating osteoclast function. A number of signalling molecules were found to be involved in the 03 integrin-dependent signalling pathway, including c-Src, Pyk2 and p130(Cas). Both Pyk2 and p130(Cas) localize to the sealing zone of actively resorbing osteoclasts, suggesting their role in linking the adhesion of osteoclasts to the bone matrix, to cytoskeletal organization, and to the polarization and activation of these cells for bone resorption. in this article, we review the regulatory mechanism of osteoclast activation.