Effects of Hyaluronic Acid on Mitochondrial Function and Mitochondria-driven Apoptosis following Oxidative Stress in Human Chondrocytes
Effects of Hyaluronic Acid on Mitochondrial Function and Mitochondria-driven Apoptosis following Oxidative Stress in Human Chondrocytes
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DOI：
10.1074/jbc.m804178200
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发表时间：
2009-04-03
影响因子：
4.8
通讯作者：
Pearsall, Albert W.
中科院分区：
文献类型：
--
作者：
Grishko, Valentina;Xu, Min;Pearsall, Albert W.
透明质酸广泛用于治疗骨关节炎，并具有显着的软骨保护作用。其软骨保护作用的确切机制尚未完全阐明。人类关节软骨细胞主动产生活性氧和氮，能够导致细胞功能障碍和死亡。越来越多的证据表明，线粒体功能障碍和线粒体 DNA 损伤在与氧自由基生成过多相关的疾病中发挥着因果作用。我们假设透明质酸对氧化应激软骨细胞的软骨保护作用是由于线粒体功能的保存和线粒体驱动的细胞凋亡的改善。当原代人类软骨细胞培养物暴露于活性氧或氮物质发生器时，线粒体 DNA 损伤以及线粒体功能障碍和线粒体驱动的细胞凋亡就会累积。此外，经过细胞因子处理的原代人软骨细胞显示线粒体 DNA 损伤水平增加。用透明质酸预处理软骨细胞可减少线粒体 DNA 损伤，增强线粒体 DNA 修复能力和细胞活力，保持 ATP 水平并改善细胞凋亡。这些研究的结果表明，氧化损伤条件下软骨细胞存活率的提高和线粒体功能的改善可能是透明质酸在骨关节炎中作用的重要治疗机制。
Hyaluronic acid is widely used in the treatment of osteoarthritis and exerts significant chondroprotective effects. The exact mechanisms of its chondroprotective action are not yet fully elucidated. Human articular chondrocytes actively produce reactive oxygen and nitrogen species capable of causing cellular dysfunction and death. A growing body of evidence indicates that mitochondrial dysfunction and mitochondrial DNA damage play a causal role in disorders linked to excessive generation of oxygen free radicals. We hypothesized that the chondroprotective effects of hyaluronic acid on oxidatively stressed chondrocytes are due to preservation of mitochondrial function and amelioration of mitochondria-driven apoptosis. When primary human chondrocyte cultures were exposed to reactive oxygen or nitrogen species generators, mitochondrial DNA damage along with mitochondrial dysfunction and mitochondria-driven apoptosis accumulated as a consequence. In addition, cytokine-treated primary human chondrocytes showed increased levels of mitochondrial DNA damage. Pretreatment of chondrocytes with hyaluronic acid caused a decrease of mitochondrial DNA damage, enhanced mitochondrial DNA repair capacity and cell viability, preservation of ATP levels, and amelioration of apoptosis. The results of these studies demonstrate that enhanced chondrocyte survival and improved mitochondrial function under conditions of oxidative injury are probably important therapeutic mechanisms for the actions of hyaluronic acid in osteoarthritis.