Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan; Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Clinical Laboratory, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
Arch Biochem Biophys. 2014 Jan 15;542:39-45. doi: 10.1016/j.abb.2013.12.002. Epub 2013 Dec 11.
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 F2α (PGF2α) on osteoprotegerin (OPG) synthesis and of resveratrol on the OPG synthesis in osteoblast-like MC3T3-E1 cells. PGF2α 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 PGF2α. Resveratrol also significantly reduced the PGF2α-stimulated OPG release and the mRNA levels of OPG. Similarly, treatment with SRT1720, an activator of SIRT1, also suppressed the PGF2α-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 PGF2α. These findings strongly suggest that resveratrol suppresses PGF2α-stimulated OPG synthesis by inhibiting the MAP kinase pathways in osteoblasts, and that the effect is mediated via SIRT1 activation.
白藜芦醇是一种在葡萄皮和红酒中大量存在的天然多酚，对人体健康具有多种有益特性。在本研究中，我们研究了前列腺素 F2α（PGF2α）对骨保护素（OPG）合成的影响以及白藜芦醇对成骨样 MC3T3-E1 细胞中 OPG 合成的影响的机制。PGF2α 刺激 OPG 蛋白的释放和 OPG mRNA 的表达。用 PD98059、SB203580 和 SP600125 处理，MEK1/2、p38 丝裂原活化蛋白激酶和应激激活蛋白激酶/c-Jun N 末端激酶（SAPK/JNK）的特异性抑制剂，均抑制 PGF2α 诱导的 OPG 释放。白藜芦醇也显著降低 PGF2α 刺激的 OPG 释放和 OPG mRNA 水平。同样，SIRT1 的激活剂 SRT1720 处理也抑制 PGF2α 刺激的 OPG 释放。白藜芦醇和 SRT1720 均可减弱 PGF2α 诱导的 p44/p42 MAP 激酶、MEK1/2、Raf-1、p38 MAP 激酶和 SAPK/JNK 的磷酸化。这些发现强烈表明，白藜芦醇通过抑制成骨细胞中的 MAP 激酶途径来抑制 PGF2α 刺激的 OPG 合成，并且该作用是通过 SIRT1 激活介导的。
