Purpose: An underlying cause of osteoarthritis (OA) is the inability of chondrocytes to maintain homeostasis in response to changing stress conditions. The purpose of this article was to review and experimentally evaluate oxidative stress resistance and resilience concepts in cartilage using glutathione redox homeostasis as an example. This framework may help identify novel approaches for promoting chondrocyte homeostasis during aging and obesity.Materials and Methods: Changes in glutathione content and redox ratio were evaluated in three models of chondrocyte stress: (1) age- and tissue-specific changes in joint tissues of 10 and 30-month old F344BN rats, including ex vivo patella culture experiments to evaluate N-acetylcysteine dependent resistance to interleukin-1beta; (2) effect of different durations and patterns of cyclic compressive loading in bovine cartilage on glutathione stress resistance and resilience pathways; (3) time-dependent changes in GSH:GSSG in primary chondrocytes from wild-type and Sirt3 deficient mice challenged with the pro-oxidant menadione.Results: Glutathione was more abundant in cartilage than meniscus or infrapatellar fat pad, although cartilage was also more susceptible to age-related glutathione oxidation. Glutathione redox homeostasis was sensitive to the duration of compressive loading such that load-induced oxidation required unloaded periods to recover and increase total antioxidant capacity. Exposure to a pro-oxidant stress enhanced stress resistance by increasing glutathione content and GSH:GSSG ratio, especially in Sirt3 deficient cells. However, the rate of recovery, a marker of resilience, was delayed without Sirt3.Conclusions: OA-related models of cartilage stress reveal multiple mechanisms by which glutathione provides oxidative stress resistance and resilience.

中文翻译：

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谷胱甘肽作为衰老和骨关节炎期间软骨氧化应激抵抗力和弹性的介质。

目的：骨关节炎 (OA) 的一个根本原因是软骨细胞无法响应不断变化的压力条件来维持体内平衡。本文的目的是以谷胱甘肽氧化还原稳态为例，回顾和实验评估软骨中的抗氧化应激和弹性概念。该框架可能有助于确定在衰老和肥胖期间促进软骨细胞稳态的新方法。 10 和 30 个月大的 F344BN 大鼠，包括离体髌骨培养实验，以评估 N-乙酰半胱氨酸对白细胞介素-1β 的依赖性；(2) 牛软骨中不同持续时间和循环压缩载荷模式对谷胱甘肽抗逆性和弹性途径的影响；(3) 用促氧化甲萘醌攻击的野生型和 Sirt3 缺陷小鼠的原代软骨细胞中 GSH:GSSG 的时间依赖性变化。对年龄相关的谷胱甘肽氧化敏感。谷胱甘肽氧化还原稳态对压缩负荷的持续时间很敏感，因此负荷诱导的氧化需要卸载期来恢复和增加总抗氧化能力。暴露于促氧化应激通过增加谷胱甘肽含量和 GSH:GSSG 比率来增强抗压性，尤其是在缺乏 Sirt3 的细胞中。然而，恢复的速度，