Volume 1068, Issue 1 p. 225-233

Interactive Effect of Interleukin-6 and Prostaglandin E2 on Osteoclastogenesis via the OPG/RANKL/RANK System

XIN-HUA LIU

XIN-HUA LIU

Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA

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ALEXANDER KIRSCHENBAUM

ALEXANDER KIRSCHENBAUM

Department of Urology, Mount Sinai School of Medicine, New York, New York 10029, USA

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SHEN YAO

SHEN YAO

Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA

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ALICE C. LEVINE

ALICE C. LEVINE

Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA

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First published: 30 May 2006
Citations: 74
Address for correspondence: Xin-Hua Liu, Department of Medicine, Box 1055, Mount Sinai School of Medicine, New York, NY 10029. Voice: 212-241-4130; fax: 212-241-4218.
 e-mail: [email protected]

Abstract

Abstract: The OPG/RANKL/RANK system regulates osteoclastogenesis. 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 EP4/EP2 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.