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

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Qin A, Cheng TS, Pavlos NJ, Lin Z, Dai KR, Zheng MH

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

Int J Biochem Cell Biol. 2012 Sep;44(9):1422-35. doi: 10.1016/j.biocel.2012.05.014. Epub 2012 May 29.

PubMed ID

22652318 [ View in PubMed

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Abstract

The vacuolar-type H(+)-ATPase (V-ATPase) proton pump is a macromolecular complex composed of at least 14 subunits organized into two functional domains, V(1) and V(0). 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.

DrugBank Data that Cites this Article

Drugs

Zoledronic acid

Tiludronic acid

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tiludronic acid	V-ATPase Subunits (Protein Group)	Protein group	Humans	Unknown	Inhibitor	Details