Resveratrol suppresses prostaglandin F_2伪-induced osteoprotegerin synthesis in osteoblasts: Inhibition of the MAP kinase signaling

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• 作者：Gen Kuroyanagi ; Haruhiko Tokuda ; Rie Matsushima-Nishiwaki ; Akira Kondo ; Jun Mizutani ; Osamu Kozawa ; Takanobu Otsuka
• 关键词：Resveratrol ; PGF2伪 ; Osteoprotegerin ; Osteoblast
• 刊名：Archives of Biochemistry and Biophysics
• 出版年：15 January, 2014
• 年：2014
• 卷：542
• 期：Complete
• 页码：39-45
• 全文大小：996 K

文摘

Resveratrol, a natural polyphenol abundantly found in grape skins and red wine, possesses various beneficial properties for human health. In the present study, we investigated the mechanism underlying the effects of prostaglandin F_2伪 (PGF_2伪) on osteoprotegerin (OPG) synthesis and of resveratrol on the OPG synthesis in osteoblast-like MC3T3-E1 cells. PGF_2伪 stimulated both the release of the OPG protein and the expression of OPG mRNA. Treatment with PD98059, SB203580 and SP600125, specific inhibitors of MEK1/2, p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) all suppressed the OPG release induced by PGF_2伪. Resveratrol also significantly reduced the PGF_2伪-stimulated OPG release and the mRNA levels of OPG. Similarly, treatment with SRT1720, an activator of SIRT1, also suppressed the PGF_2伪-stimulated OPG release. Resveratrol and SRT1720 both attenuated the phosphorylation of p44/p42 MAP kinase, MEK1/2, Raf-1, p38 MAP kinase and SAPK/JNK induced by PGF_2伪. These findings strongly suggest that resveratrol suppresses PGF_2伪-stimulated OPG synthesis by inhibiting the MAP kinase pathways in osteoblasts, and that the effect is mediated via SIRT1 activation.