Mechanisms controlling vacuolar H+-adenosine triphosphatase activity: targets for the development of new therapeutic agents for the management of osteoporosis

Abstract

See, stats, and : https : / / www . researchgate. net / publication / 235230506 Mechanisms - adenopsine : targets the the . Article CITATION 1 READS 45 4 , including : Lexie University 78 , 735 SEE Nancy University 1 SEE All - text , letting . Available : Lexie Retrieved : 05 Abstract : Recent genetic studies show that mutations in vacuolar H + - adenosine triphosphatase (V - ATPase) subunit isoforms that are selectively expressed in osteoclasts (a3 and d2) lead to both reduced bone resorption and increased bone formation . This implies that pharmaceuticals targeting these subunits or activities that are linked to these subunits might prove to be bone anabolic . The fact that V - ATPase is a ubiquitous " housekeeping " enzyme has made it challenging to directly target the enzymatic activity of the subset of V - ATPases involved in bone resorption ; however , the unique mechanisms that control the V - ATPases involved in bone resorption have begun to emerge . These include binding interactions with the cytoskeleton and with proteins involved in regulating the cytoskeleton and membrane trafficking , links to glycolysis , and surpris - ing ties to the renin – angiotensin signaling network . Links between controlling mechanisms and subunit a3 have been identified , suggesting that it may be possible to develop agents that disrupt bone resorptive V - ATPase activity while leaving the housekeeping activities unhindered . The first steps toward using this new information to rationally design novel classes of therapeutic agents have been taken . Such agents might selectively act against osteoclasts both to prevent the initiation of osteoporosis and to restore already - compromised bone .