Interactive Effect of Interleukin-6 and Prostaglandin E_2 on Osteoclastogenesis via the OPG/RANKL/RANK System

摘要

The OPG/RANKL/RANK system regulates osteoclastoge-nesis. Both cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and interleukin-6 (IL-6) are reported to induce osteoclast differentiation. The mechanisms underlying these signaling pathways on the OPG/RANKL/ RANK system are not fully understood. We herein demonstrate that COX-2 and PGE2 stimulated Osteoclastogenesis through inhibition of OPG secretion, stimulation of RANKL production by osteoblasts, and upregulation of RANK expression in osteoclasts. PGE2 also stimulated IL-6 production, and IL-6, in turn, increased PGE2 secretion, COX-2, and EP_4/EP_2 expression in bone cells. These findings provide evidence of interactive effect of PGE2 and IL-6 signaling pathways in Osteoclastogenesis via effect on the OPG/RANKL/RANK system.