Interactive effect of interleukin-6 and prostaglandin E2 on osteoclastogenesis via the OPG/RANKL/RANK system.
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.
Liu
Xin-Hua
XH
Department of Medicine, Box 1055, Mount Sinai School of Medicine, New York, NY 10029. Liu.Xinhua@mssm.edu.
Kirschenbaum
Alexander
A
Yao
Shen
S
Levine
Alice C
AC
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D018920:Coculture Techniques; D015232:Dinoprostone / Q000494:pharmacology*; D006023:Glycoproteins / Q000502:physiology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*
D002352:Carrier Proteins; D006023:Glycoproteins; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D015232:Dinoprostone