Inflammatory cytokines activate p38 MAPK to induce osteoprotegerin synthesis by MG-63 cells |
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Authors: | Pantouli Ekaterini Boehm Matthew M Koka Sreenivas |
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Institution: | Department of Oral Biology, UNMC College of Dentistry, Lincoln, NE, USA. |
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Abstract: | Inflammatory bone diseases are characterized by the presence of pro-inflammatory cytokines that regulate bone turnover. Osteoprotegerin (OPG) is a soluble osteoblast-derived protein that influences bone resorption by inhibiting osteoclast differentiation and activation. In the present study, we demonstrate that interleukin-1beta and tumor necrosis factor alpha induce OPG mRNA production and OPG secretion by osteoblast-like MG-63 cells. Maximum induction of OPG secretion by either cytokine requires activation of the p38 mitogen activated protein kinase (MAPK) pathway but neither the p42/p44 (ERK) nor the c-Jun N-terminal MAPK pathways. Induction of OPG mRNA by either cytokine is also p38 MAPK dependent. Taken together, these data indicate that cytokine-induced OPG gene expression and protein secretion are differentially regulated by specific MAP kinase signal transduction pathways. |
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Keywords: | Osteoblast Signal transduction Osteoprotegerin MAP kinase Inflammatory cytokine IL-1β TNF-α |
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