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Interactive Effect of Interleukin‐6 and Prostaglandin E 2 on Osteoclastogenesis via the OPG/RANKL/RANK System
Author(s) -
LIU XINHUA,
KIRSCHENBAUM ALEXANDER,
YAO SHEN,
LEVINE ALICE C.
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1346.047
Subject(s) - rankl , osteoclast , chemistry , rank ligand , prostaglandin e2 , cyclooxygenase , prostaglandin e2 receptor , downregulation and upregulation , bone resorption , secretion , stimulation , medicine , interleukin , prostaglandin , signal transduction , endocrinology , microbiology and biotechnology , cytokine , biology , receptor , enzyme , biochemistry , activator (genetics) , gene , agonist
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 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.