Resveratrol prevents RANKL-induced osteoclast differentiation of murine osteoclast progenitor RAW 264.7 cells through inhibition of ROS production
Resveratrol prevents RANKL-induced osteoclast differentiation of murine osteoclast progenitor RAW 264.7 cells through inhibition of ROS production
复制标题
DOI：
10.1016/j.bbrc.2010.09.053
复制
发表时间：
2010-10-22
影响因子：
3.1
通讯作者：
Li, Yan
中科院分区：
文献类型：
--
作者：
He, Xu;Andersson, Goran;Li, Yan
白藜芦醇的骨保护作用已在几种骨质疏松模型中得到证实，但其潜在机制尚不清楚。在本研究中，我们评估了白藜芦醇对小鼠破骨细胞祖细胞RAW 264.7细胞的分化和凋亡的影响。我们发现，在无毒浓度的白藜芦醇剂量依赖性地抑制RANKL诱导的破骨细胞分化和诱导凋亡。白藜芦醇已被证明是Sirt 1（一种NAD（+）依赖性蛋白脱乙酰酶）的激活剂，并已被证明模拟雌激素。然而，我们发现，尽管Sirt 1蛋白在RAW264.7细胞中大量表达，但特异性Sirt 1抑制剂EX-527不能减弱白藜芦醇介导的破骨细胞生成抑制。高亲和力雌激素受体拮抗剂ICI-182780不能减弱白藜芦醇的作用。活性氧（ROS）在RANKL诱导的破骨细胞分化中的核心作用最近已被阐明。我们发现，白藜芦醇抑制RANKL诱导的活性氧产生的浓度依赖性的方式。我们推测白藜芦醇对破骨细胞生成的直接抑制作用是通过抑制ROS的产生来介导的。(C)2010年爱思唯尔公司All rights reserved.
The bone protective effects of resveratrol have been demonstrated in several osteoporosis models while the underlying mechanism is largely unclear. In the present study, we evaluated the effects of resveratrol on differentiation and apoptosis of murine osteoclast progenitor RAW 264.7 cells. We found that resveratrol at non-toxic concentrations dose-dependently inhibited RANKL-induced osteoclast differentiation and induced apoptosis. Resveratrol has been shown to be an activator of Sirt1, a NAD(+) dependent protein deacetylase, and has been demonstrated to mimic estrogen. However, we found that although Sirt1 protein was abundantly expressed in RAW264.7 cells, the specific Sirt1 inhibitor EX-527 could not attenuate the inhibition of osteoclastogenesis mediated by resveratrol. Also, the effects of resveratrol could not be attenuated by ICI-182780, a high affinity estrogen receptor antagonist. The central role of reactive oxygen species (ROS) in RANKL-induced osteoclast differentiation has recently been clarified. We found that resveratrol suppressed RANKL-induced ROS generation in a concentration dependent manner. We postulate that the direct inhibitory effects of resveratrol on osteoclastogenesis are mediated via inhibition of ROS generation. (C) 2010 Elsevier Inc. All rights reserved.