The vacuolar ATPase in bone cells: a potential therapeutic target in osteoporosis.
The vacuolar ATPase (V-ATPase) is a multisubunit enzyme that couples ATP hydrolysis to proton pumping across membranes. Recently, there is increasing evidence that V-ATPase may contribute to the pathogenesis of bone resorption disorders due to it is predominantly expressed in osteoclasts also function in bone resorption making it a good candidate in a therapeutic target for osteoporosis. Osteoclasts are capable of generating an acidic microenvironment necessary for bone resorption by utilizing V-ATPases to pump protons into the resorption lacuna. In addition, it has been shown that therapeutic interventions have been proposed that specifically target inhibition of the osteoclast proton pump. Modulation of osteoclastic V-ATPase activity has been considered to be a suitable therapy for the treatment of osteoporosis. All theses findings suggest that V-ATPase have important biological effects in bone resorption that might be a promising therapeutic target for osteoporosis. In this review, we will briefly discuss the biological features of osteoporosis and summarize recent advances on the role of V-ATPase in the pathogenesis and treatment of osteoporosis.
Yuan
Feng-Lai
FL
The Third Hospital Affiliated to Nantong University, Wuxi, Jiangsu, 214041, People's Republic of China. bjjq88@163.com
Li
Xia
X
Lu
Wei-Guo
WG
Li
Cheng-Wan
CW
Li
Jian-Ping
JP
Wang
Yu
Y
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010024:Osteoporosis / Q000188:drug therapy* / Q000201:enzymology* / Q000209:etiology; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D004791:Enzyme Inhibitors; D021122:Protein Subunits; D025262:Vacuolar Proton-Translocating ATPases