Secreted phospholipase A2 type II is present in Paget's disease of bone and modulates osteoclastogenesis, apoptosis and bone resorption of human osteoclasts independently of its catalytic activity in vitro

ObjectivesTo study the role of secreted phospholipase A2 (sPLA2) in the pathophysiology of human osteoclasts (OCs).MethodsImmunohistochemistry and sPLA2 inhibitors were to determine the localization of sPLA2 and its role in OCs biology.ResultssPLA2 is expressed by OCs from healthy fetal bone and OCs from Paget's disease but not in normal bone. Inhibition of sPLA2 greatly reduces in vitro osteoclastogenesis.DiscussionThe decrease in OCs formed could be attributed to a decline in the viability of CD14+ OC precursors as well as a reduced viability of mature OCs. Inhibition of sPLA2 strongly decreases bone resorption by OCs independently of actin cytoskeleton remodeling, probably also by reducing OCs viability.ConclusionHigh amounts of this enzyme are present in fetal and Pagetic bone samples. Inhibition of sPLA2in vitro decreases osteoclastogenesis and OC activity and might constitute an interesting pharmacologic target for diseases with high bone turnover.