Cytosolic phospholipase A2 and eicosanoids modulate life, death and function of human osteoclasts in vitro

Abstract

Introduction: Eicosanoids are important in bone physiology but the specific function of phopholipase enzymes has not been determined in osteoclasts. The objective of this is study was to determine the presence of cPLA2 in human in vitro-differentiated osteoclasts as well as osteoclasts in situ from bone biopsies.

Materials and methods: Osteoclastogenesis, apoptosis, bone resorption and the modulation of actin cytoskeleton assays were performed on osteoclasts differentiated in vitro. Immunohistochemistry was done in differentiated osteoclasts as well as on bone biopsies.

Results: Human osteoclasts from normal, fetal, osteoarthritic, osteoporotic and Pagetic bone biopsies express cPLA2 and stimulation with RANKL increases cPLA2 phosphorylation in vitro. Inhibition of cPLA2 increased osteoclastogenesis and decreased apoptosis but decreased the capacity of osteoclasts to generate actin rings and to resorb bone.

Discussion and conclusions: These results suggest that cPLA2 modulates osteoclast functions and could be a useful target in bone diseases with hyperactivated osteoclasts.

Keywords: Bone; Eicosanoids; Osteoclasts; Phospholipases; Prostaglandins.