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V-ATPases in osteoclasts: Structure, function and potential inhibitors of bone resorption

2012; Elsevier BV; Volume: 44; Issue: 9 Linguagem: Inglês

10.1016/j.biocel.2012.05.014

1878-5875

An Qin, Tsung‐Yen Cheng, Nathan J. Pavlos, Zhen Lin, Kerong Dai, Minghao Zheng,

Macrophage Migration Inhibitory Factor

The vacuolar-type H+-ATPase (V-ATPase) proton pump is a macromolecular complex composed of at least 14 subunits organized into two functional domains, V1 and V0. The complex is located on the ruffled border plasma membrane of bone-resorbing osteoclasts, mediating extracellular acidification for bone demineralization during bone resorption. Genetic studies from mice to man implicate a critical role for V-ATPase subunits in osteoclast-related diseases including osteopetrosis and osteoporosis. Thus, the V-ATPase complex is a potential molecular target for the development of novel anti-resorptive agents useful for the treatment of osteolytic diseases. Here, we review the current structure and function of V-ATPase subunits, emphasizing their exquisite roles in osteoclastic function. In addition, we compare several distinct classes of V-ATPase inhibitors with specific inhibitory effects on osteoclasts. Understanding the structure-function relationship of the osteoclast V-ATPase may lead to the development of osteoclast-specific V-ATPase inhibitors that may serve as alternative therapies for the treatment of osteolytic diseases.