The role of V-ATPase accessory subunit Ac45 in osteoclasts

破骨细胞与许多溶骨性疾病直接相关，包括骨质疏松症、骨关节炎和佩吉特病。控制破骨细胞的形成和活动的策略的发展一直是骨研究的主要焦点。位于破骨细胞质膜上的液泡质子泵（V-ATPase）负责产生对骨吸收至关重要的低pH环境，因此是发现用于治疗溶骨性疾病的新型骨抗吸收剂的潜在分子靶点。该研究将为破骨细胞中V-ATP酶辅助亚基Ac 45和V-ATP酶复合体的作用提供重要的信息。了解V-ATP酶调节破骨细胞骨吸收的分子和细胞机制，将有助于开发新的和选择性的抑制剂，用于治疗溶骨性疾病。

Osteoclasts are directly related to many lytic bone disorders including osteoporosis, osteoarthritis and Paget's diseases. Development of strategies to control the formation or activities of osteoclasts has been a major focus of bone research. The vacuolar proton pump (V-ATPase) located on the plasma membrane of the osteoclast is responsible for creating a low pH environment critical for bone resorption, and therefore a potential molecular target for the discovery of novel bone antiresorptive agents useful for the treatment of lytic bone disorders. The proposed research will give considerable insight into the role of the both V-ATPase accessory subunit Ac45 and V-ATPase complex in osteoclasts. Understanding the molecular and cellular mechanisms by which V-ATPases regulate osteoclast bone resorption will facilitate the development of novel and selective inhibitors for the treatment of lytic bone disorders.