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

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 cPLA(2) in human in vitro-differentiated osteodasts 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 osteodasts from normal, fetal, osteoarthritic, osteoporotic and Pagetic bone biopsies express cPLA(2) and stimulation with RANKL increases cPLA(2) phosphotylation in vitro. Inhibition of cPLA(2) 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 cPLA(2) modulates osteodast functions and could be a useful target in bone diseases with hyperactivated osteoclasts. (C) 2014 Elsevier Ltd. All rights reserved.