Nakamura Ichiro, Rodan Gideon A, Duong Le T
Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo, Japan.
J Electron Microsc (Tokyo). 2003;52(6):527-33. doi: 10.1093/jmicro/52.6.527.
Osteoclasts are multinucleated, terminally differentiated cells which play an essential role in bone resorption. Osteoclasts exhibit high expression of the alpha(v)beta3 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)beta3 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 alpha(v)beta3 integrin-dependent signalling pathway, including c-Src, Pyk2 and p130Cas. Both Pyk2 and p130Cas 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.
破骨细胞是多核的终末分化细胞，在骨吸收中起重要作用。破骨细胞高表达α(v)β3整合素，该整合素可与多种细胞外基质蛋白结合，包括玻连蛋白、骨桥蛋白和骨唾液蛋白。含RGD（精氨酸-甘氨酸-天冬氨酸）的肽、RGD模拟物以及α(v)β3整合素阻断抗体在体外和体内均显示出抑制骨吸收的作用，这表明该整合素在调节破骨细胞功能中起重要作用。已发现多种信号分子参与α(v)β3整合素依赖性信号通路，包括c-Src、Pyk2和p130Cas。Pyk2和p130Cas均定位于活跃进行骨吸收的破骨细胞的封闭带，提示它们在将破骨细胞与骨基质的黏附、细胞骨架组织以及这些细胞的极化和激活与骨吸收联系起来方面发挥作用。在本文中，我们综述了破骨细胞激活的调节机制。
