Runx2-Mediated bcl-2 Gene Expression Contributes to Nitric Oxide Protection Against Hydrogen Peroxide-induced Osteoblast Apoptosis
Runx2-Mediated bcl-2 Gene Expression Contributes to Nitric Oxide Protection Against Hydrogen Peroxide-induced Osteoblast Apoptosis
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DOI：
10.1002/jcb.22338
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发表时间：
2009-12-01
影响因子：
4
通讯作者：
Chen, Ruei-Ming
中科院分区：
文献类型：
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作者：
Ho, Wei-Pin;Chan, Wing-Pong;Chen, Ruei-Ming
一氧化氮（NO）可调节成骨细胞的活性。本研究旨在探讨硝普钠（SNP）预处理对过氧化氢诱导成骨细胞损伤的保护作用及其可能机制。人骨肉瘤MG 63细胞暴露于过氧化氢显著增加细胞的氧化应激，但降低ALP活性和细胞活力，诱导细胞凋亡。用0.3 mM SNP预处理显著降低过氧化氢诱导的细胞损伤。用过氧化氢处理人MG 63细胞抑制Bcl-2 mRNA和蛋白质的产生，但用0.3 mM SNP预处理显著改善了这种抑制。随后，过氧化氢降低线粒体膜电位，但增加细胞色素c和caspase-3活性的水平。用0.3 mM SNP预处理显著降低了这种改变。暴露于过氧化氢降低Runx 2 mRNA和蛋白质的合成。然而，0.3mM SNP预处理显著降低了抑制作用。Runx 2基因的RNA干扰抑制了人MG 63细胞Bcl-2 mRNA的表达。0.3 mM SNP预处理对过氧化氢诱导的ALP活性、caspase-3活性、凋亡细胞和细胞活力的改变的保护作用也在Runx 2小干扰RNA给药后减轻。因此，本研究表明，预处理与0.3 mM SNP可以保护人MG 63细胞从过氧化氢诱导的凋亡损伤可能通过Runx 2参与的bcl-2基因表达的调节。J.细胞。108：1084-1093，2009. (C)2009 Wiley-Liss，Inc.
Nitric oxide (NO) can regulate osteoblast activities. This study was aimed to evaluate the protective effects of pretreatment with sodium nitroprusside (SNP) as a source of NO on hydrogen peroxide-induced osteoblast insults and its possible mechanisms. Exposure of human osteosarcoma MG63 cells to hydrogen peroxide significantly increased cellular oxidative stress, but decreased ALP activity and cell viability, inducing cell apoptosis. Pretreatment with 0.3 mM SNP significantly lowered hydrogen peroxide-induced cell insults. Treatment of human MG63 cells with hydrogen peroxide inhibited Bcl-2 mRNA and protein production, but pretreatment with 0.3 mM SNP significantly ameliorated such inhibition. Sequentially, hydrogen peroxide decreased the mitochondrial membrane potential, but increased the levels of cytochrome c and caspase-3 activity. Pretreatment with 0.3 mM SNP significantly lowered such alterations. Exposure to hydrogen peroxide decreased Runx2 mRNA and protein syntheses. However, pretreatment with 0.3 mM SNP significantly lowered the suppressive effects. Runx2 knockdown using RNA interference inhibited Bcl-2 mRNA production in human MG63 cells. Protection of pretreatment with 0.3 mM SNP against hydrogen peroxide-induced alterations in ALP activity, caspase-3 activity, apoptotic cells, and cell viability were also alleviated after administration of Runx2 small interference RNA. Thus, this study shows that pretreatment with 0.3 mM SNP can protect human MG63 cells from hydrogen peroxide-induced apoptotic insults possibly via Runx2-involved regulation of bcl-2 gene expression. J. Cell. Biochem. 108: 1084-1093, 2009. (C) 2009 Wiley-Liss, Inc.