SOLUBLE PHOSPHOLIPASEA_2 IN THE LIFE AND DEATH OF OSTEOCLASTS

Abstract

Background: Prostaglandins are important for the control of bone remodeling; phospholipases A_2 are essential for prostaglandin synthesis and could be an important mediator for bone health. Our objective was to determine the role of sPLA_2 on osteoclastogenesis and osteoclast (OC) apoptosis. Methods: Human osteoclasts were differentiated in vitro from PBMC in the presence of RANKL and M-CSF. The presence of sPLA_2 was confirmed by immunohistochemistry in OCs in culture and on bone slices. The role of sPLA2 II on osteoclastogenesis and on OC apoptosis was studied using sPLA2 inhibitors The implication of sPLA2 II in bone remodeling in vivo was determined by comparing levels of the enzyme in the peripheral blood ofpatients with traumatic fracture compared to age- and sex-matched controls. Results: In vitrodifferentiated osteoclasts and in situ fetal and Pagetic bone osteoclasts express sPLA_2 II. sPLA_2II inhibition during osteoclastogenesis reduces the capacity to generateosteoclasts and increases apoptosis rate of osteoclastic precursors; it also induces apoptosis on mature OCs. Patients with bone fractures have significantly less circulating sPLA_2 II than controls. Conclusion: sPLA_2 II is present in OCs both invitro and in vivo, in normal as well as in pathologic situations. Its inhibition reduces osteoclastogenesis and increases apoptosis rate in vitro. Plasmatic sPLA_2 II levels are lower post-fracture than in controls. These results strongly suggest a role for sPLA2in the control of bone metabolism but the mechanisms implicated in this effects still need to be clarified.