Integrins and signaling in osteoclast function.
Integrins are heterodimeric adhesion receptors that mediate cell-matrix and cell-cell interactions. Osteoclasts highly express the alphavbeta3 integrin, which binds to a variety of extracellular matrix proteins including vitronectin, osteopontin and bone sialoprotein. RGD-containing peptides, RGD-mimetics and alphavbeta3 blocking antibodies inhibit bone resorption in vitro and in vivo, suggesting that this integrin plays an important role in osteoclast function. RGD-containing peptides were shown to raise cytosolic calcium in osteoclasts. Furthermore, several signaling and adaptor molecules were found to be involved in alphavbeta3 integrin-dependent signaling pathways, including phosphatidylinositol 3-kinase, c-Src, PYK2 and p130(cas). In addition, cytoskeletal molecules such as paxillin, vinculin, gelsolin and F-actin are recruited to adhesion contacts upon integrin activation. Many of these molecules signaling and cytoskeletal localize to the sealing zone of actively resorbing osteoclasts, suggesting that they play a role in linking the adhesion of osteoclasts to the bone matrix with the cytoskeletal organization and the polarization and activation of these cells for bone resorption.
Duong
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LT
Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, PA 19486, USA. duong@merck.com
Lakkakorpi
P
P
Nakamura
I
I
Rodan
G A
GA
D000818:Animals; D006801:Humans; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D019030:Receptors, Vitronectin