Resveratrol Attenuates Lipopolysaccharides (LPS)-Induced Inhibition of Osteoblast Differentiation in MC3T3-E1 Cells.
Resveratrol Attenuates Lipopolysaccharides (LPS)-Induced Inhibition of Osteoblast Differentiation in MC3T3-E1 Cells.
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白藜芦醇可减弱脂多糖 (LPS) 诱导的 MC3T3-E1 细胞成骨细胞分化抑制。
DOI：
10.12659/msm.905703
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发表时间：
2018-04-06
期刊：
影响因子：
--
通讯作者：
Chen A
中科院分区：
文献类型：
--
作者：
Ma J;Wang Z;Zhao J;Miao W;Ye T;Chen A
脂多糖抑制成骨细胞分化在骨髓炎的发病机制中起重要作用。因此，寻找影响脂多糖介导的成骨细胞分化的药物可能是开发骨髓炎治疗方法的关键。本研究旨在探讨红酒中的天然多酚白藜芦醇对脂多糖抑制成骨细胞分化的作用及其机制。采用MMT法测定细胞活力。测定线粒体ATP水平、膜电位和超氧化物生成，以评估LPS和白藜芦醇对成骨细胞样MC3T3-E1细胞线粒体功能的影响。采用酶联免疫吸附法和RT-PCR检测经LPS和白藜芦醇处理的成骨细胞中ALP、OCN、OPN、RUNX2等成骨相关基因。Western blot检测细胞Sirt1和PCG-1α水平，探讨白藜芦醇处理对lps刺激的MC3T3-E1成骨细胞的影响。结果显示，LPS可引起MC3T3-E1细胞线粒体功能障碍，且呈剂量依赖性，白藜芦醇可减轻线粒体功能障碍。此外，在成骨分化培养基中培养的MC3T3-E1细胞中，LPS显著降低了ALP、OCN、OPN和RUNX2的表达，表明LPS抑制了MC3T3-E1细胞的成骨分化。而白藜芦醇能明显缓解LPS对成骨细胞分化的抑制作用。此外，白藜芦醇增加了LPS处理MC3T3-E1细胞中Sirt1和PGC-1α的表达。综上所述，这些结果表明，白藜芦醇通过改善（至少部分）线粒体功能，减轻了LPS对成骨细胞分化的抑制。
LPS-inhibited osteoblastic differentiation plays an important role in the pathogenesis of osteomyelitis. Thus, searching for drugs that affect LPS-mediated osteoblastic differentiation may be crucial in developing therapies for osteomyelitis. The purpose of this study was to investigate the role and mechanisms of resveratrol, a natural polyphenol present in red wine, on LPS-inhibited osteoblastic differentiation. Cell viability was measured by MMT assay. Mitochondrial ATP levels, membrane potential, and superoxide production were measured to evaluate the effects of LPS and resveratrol on mitochondrial functions in osteoblast-like MC3T3-E1 cells. Osteoblast-related genes, including ALP, OCN, OPN, and RUNX2, were measured by ELISA analysis and RT-PCR in differentiated osteoblast cells treated with LPS and resveratrol. Cellular Sirt1 and PCG-1α levels were measured by Western blot to probe the impact of resveratrol treatment in LPS-stimulated MC3T3-E1 osteoblasts. The results showed that LPS caused significant mitochondrial dysfunctions of MC3T3-E1 cells in a dose-dependent manner, which were attenuated by resveratrol. Furthermore, LPS markedly decreased the expression of ALP, OCN, OPN, and RUNX2 in MC3T3-E1 cells cultivated in osteoblast differentiation medium, suggesting that LPS inhibited the osteoblastic differentiation of MC3T3-E1 cells. However, resveratrol obviously alleviated the suppressive impact of LPS on osteoblast differentiation. In addition, resveratrol increased expression of Sirt1 and PGC-1α in MC3T3-E1 cells treated with LPS. Taken together, these results show that resveratrol alleviated the suppression of LPS on osteoblast differentiation by improving, at least in part, mitochondrial function.
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