Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China.
Mol Med Rep. 2012 Feb;5(2):483-8. doi: 10.3892/mmr.2011.641. Epub 2011 Oct 19.
Apoptosis of osteoblasts has been proposed as the common basis of osteoporosis, with oxidative stress as the major cause. This study was performed to investigate the protective effect of simvastatin (0.001-0.1 µM) on 100 µM hydrogen peroxide (H2O2)-mediated oxidative stress-induced apoptosis in human osteosarcoma (MG63) cells and the molecular mechanisms involved. Cell apoptosis was evaluated by observation of morphological changes and Annexin V-propidium iodide double staining followed by flow cytometric analysis. MTS assays were used to evaluate cell viability. To investigate the underlying molecular mechanisms, the expression of caspase-3, caspase-9 and Bcl-2 were analyzed by Western blotting. Following stimulation with H2O2 for 24 h, a high proportion of MG63 cells underwent apoptosis, while a dose-dependent inhibition of apoptosis was observed in the presence of simvastatin. A significant, dose-dependent reduction in the expression of caspase-3 and caspase-9 protein induced by H2O2 in MG63 cells was observed in response to simvastatin and the Bcl-2 levels were increased. In conclusion, simvastatin protects MG63 cells from oxidative stress-induced apoptosis through downregulation of caspase-3 and caspase-9 activation and upregulation of Bcl-2 expression, suggesting a protective effect in osteoporosis.
成骨细胞凋亡被认为是骨质疏松症的共同基础，氧化应激是主要原因。本研究旨在探讨辛伐他汀（0.001-0.1 μM）对 100 μM 过氧化氢（H2O2）介导的氧化应激诱导的人骨肉瘤（MG63）细胞凋亡的保护作用及其相关分子机制。通过观察形态变化和 Annexin V-碘化丙啶双重染色，然后进行流式细胞术分析来评估细胞凋亡。采用 MTS 法评估细胞活力。为了探讨潜在的分子机制，采用 Western blot 分析检测 caspase-3、caspase-9 和 Bcl-2 的表达。在 H2O2 刺激 24 h 后，MG63 细胞发生了高比例的凋亡，而辛伐他汀存在时则观察到凋亡的剂量依赖性抑制。辛伐他汀还能显著下调 H2O2 诱导的 MG63 细胞中 caspase-3 和 caspase-9 蛋白的表达，同时增加 Bcl-2 水平。综上所述，辛伐他汀通过下调 caspase-3 和 caspase-9 的激活以及上调 Bcl-2 的表达，保护 MG63 细胞免受氧化应激诱导的凋亡，提示其在骨质疏松症中有保护作用。
