The role of mitochondrial reactive oxygen species in cartilage matrix destruction
The role of mitochondrial reactive oxygen species in cartilage matrix destruction
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DOI：
10.1007/s11010-014-2187-z
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发表时间：
2014-08
影响因子：
4.3
通讯作者：
Kendra N. Reed;G. Wilson;A. Pearsall;V. Grishko
中科院分区：
文献类型：
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作者：
Kendra N. Reed;G. Wilson;A. Pearsall;V. Grishko
基质金属蛋白酶（MMPs）的上调是骨关节炎进展的标志;沿着活性氧（ROS）可能在此过程中发挥作用。此外，线粒体DNA损伤和功能障碍也存在于骨关节炎软骨细胞中。然而，目前还没有研究报道线粒体ROS、线粒体DNA损伤和MMP表达之间的直接关系。因此，本研究的目的是评估是否线粒体DNA损伤和脑源性氧化应激调节基质破坏通过MMP蛋白水平的上调。MitoSox red用于观察线粒体ROS的产生，而定量Southern印迹技术用于分析线粒体DNA损伤。此外，Western印迹分析用于确定MMP蛋白水平。本研究的结果表明，甲萘醌增加了脑组织产生的ROS，并增加了线粒体DNA损伤。细胞产生的ROS的增加导致MMP水平的增加。当加入线粒体ROS清除剂时，MMP水平随后降低。这些研究表明，线粒体的完整性是通过改变MMP水平来维持软骨基质所必需的。这为线粒体在软骨细胞功能中的作用及其在治疗方法中的潜在重要性提供了新的重要见解。
Upregulation of matrix metalloproteinases (MMPs) is a hallmark of osteoarthritis progression; along with the role reactive oxygen species (ROS) may play in this process. Moreover, mitochondrial DNA damage and dysfunction are also present in osteoarthritic chondrocytes. However, there are no studies published investigating the direct relationship between mitochondrial ROS, mitochondrial DNA damage, and MMP expression. Therefore, the purpose of the present study was to evaluate whether mitochondrial DNA damage and mitochondrial-originated oxidative stress modulates matrix destruction through the upregulation of MMP protein levels. MitoSox red was utilized to observe mitochondrial ROS production while a Quantitative Southern blot technique was conducted to analyze mitochondrial DNA damage. Additionally, Western blot analysis was used to determine MMP protein levels. The results of the present study show that menadione augmented mitochondrial-generated ROS and increased mitochondrial DNA damage. This increase in mitochondrial-generated ROS led to an increase in MMP levels. When a mitochondrial ROS scavenger was added, there was a subsequent reduction in MMP levels. These studies reveal that mitochondrial integrity is essential for maintaining the cartilage matrix by altering MMP levels. This provides new and important insights into the role of mitochondria in chondrocyte function and its potential importance in therapeutic approaches.