Injurious Loading of Articular Cartilage Compromises Chondrocyte Respiratory Function.
Injurious Loading of Articular Cartilage Compromises Chondrocyte Respiratory Function.
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DOI：
10.1002/art.39460
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Martin JA
中科院分区：
文献类型：
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作者：
Coleman MC;Ramakrishnan PS;Brouillette MJ;Martin JA
确定反复超负荷的健康软骨是否会以与骨关节炎发病机制类似的方式破坏线粒体功能。我们将牛骨软骨外植体上的正常关节软骨暴露于 1 天或连续 7 天的循环轴向压缩（0.25 或 1.0 MPa，0.5 Hz，3 小时），并评估对软骨细胞活力、ATP 浓度、活性氧 (ROS) 产生、氧化应激指标、呼吸和线粒体膜电位的影响。 0.25 MPa 和 1.0 MPa 的循环压缩都不会导致广泛的软骨细胞死亡、宏观组织损伤或应力应变行为的明显变化。负载一天后，0.25 MPa 和 1.0 MPa 组之间的呼吸活动差异很小；然而，在 7 个负载天后，相对于 0.25 MPa 组，1.0 MPa 组的呼吸活动和 ATP 水平受到抑制，用 10 mM N-乙酰半胱氨酸预处理可以防止这种影响。这些变化伴随着质子泄漏的增加和线粒体膜电位的降低，以及二氢乙锭染色和谷胱甘肽氧化表明的ROS形成的增加。反复超负荷会导致软骨细胞氧化依赖性线粒体功能障碍。这种线粒体功能障碍可能会破坏软骨细胞对机械刺激的合成代谢反应，以不同的方式导致骨关节炎各个阶段的软骨不稳定。
Determine whether repeatedly overloading healthy cartilage disrupts mitochondrial function in a manner similar to that associated with osteoarthritis pathogenesis. We exposed normal articular cartilage on bovine osteochondral explants to 1 day or 7 consecutive days of cyclic axial compression (0.25 or 1.0 MPa, 0.5 Hz, 3 hours) and evaluated effects on chondrocyte viability, ATP concentration, reactive oxygen species (ROS) production, indicators of oxidative stress, respiration, and mitochondrial membrane potential. Neither 0.25 nor 1.0 MPa cyclic compression caused extensive chondrocyte death, macroscopic tissue damage, or overt changes in stress-strain behavior. After one day of loading, differences in respiratory activities between the 0.25 and 1.0 MPa groups were minimal; after 7 loading days, however, respiratory activity and ATP levels were suppressed in the 1.0 MPa group relative to the 0.25 MPa group, an effect prevented with pretreatment with 10 mM N-acetylcysteine. These changes were accompanied by increased proton leakage and decreases in mitochondrial membrane potential as well as by increased ROS formation indicated by dihydroethidium staining and glutathione oxidation. Repeated overloading leads to chondrocyte oxidant-dependent mitochondrial dysfunction. This mitochondrial dysfunction may contribute to destabilization of cartilage during various stages of OA in distinct ways by disrupting chondrocyte anabolic responses to mechanical stimuli.