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.
MeSH terms
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3T3 Cells
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Animals
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Carrier Proteins / physiology*
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Cell Division / drug effects
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Cell Line
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Coculture Techniques
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Dinoprostone / pharmacology*
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Glycoproteins / physiology*
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Interleukin-6 / pharmacology*
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Macrophages / cytology
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Membrane Glycoproteins / physiology*
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Mice
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Osteoblasts / cytology*
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Osteoblasts / drug effects
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Osteoblasts / physiology*
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Osteoclasts / drug effects
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Osteoclasts / physiology*
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Osteogenesis / drug effects
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Osteogenesis / physiology*
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Osteoprotegerin
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Cytoplasmic and Nuclear / physiology*
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Receptors, Tumor Necrosis Factor / physiology*
Substances
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Carrier Proteins
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Glycoproteins
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Interleukin-6
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Membrane Glycoproteins
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Osteoprotegerin
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Cytoplasmic and Nuclear
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Receptors, Tumor Necrosis Factor
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Tnfrsf11a protein, mouse
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Tnfrsf11b protein, mouse
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Tnfsf11 protein, mouse
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Dinoprostone