Osteoarthritis (OA) is the most common form of arthritis worldwide with no effective treatment. Ageing is the primary risk factor for OA. We sought to investigate if there is a distinct and functional convergence of ageing-related mechanisms SIRT1 and autophagy in chondrocytes. Our results show that, levels of SIRT1 are decreased in human normal aged and OA cartilage compared with young cartilage. Moreover, silencing SIRT1 in chondrocytes lead to decreased expression of chondrogenic markers but did not alter the expression of catabolic proteases. In contrast, activation of SIRT1 increased autophagy in chondrocytes by the deacetylation of lysine residues on crucial autophagy proteins (Beclin1, ATG5, ATG7, LC3). This activation was shown to be mTOR/ULK1 independent. Our results indicate that maintenance of autophagy in chondrocytes by SIRT1 is essential for preserving cartilage integrity throughout life and therefore is a target for drug intervention to protect against OA.

骨关节炎（OA）是全世界最常见的关节炎形式，目前尚无有效的治疗方法。衰老是 OA 的主要危险因素。我们试图研究软骨细胞中衰老相关机制 SIRT1 和自噬是否存在明显的功能性趋同。我们的结果表明，与年轻软骨相比，人类正常老年人和 OA 软骨中 SIRT1 的水平降低。此外，沉默软骨细胞中的 SIRT1 会导致软骨形成标记物的表达减少，但不会改变分解代谢蛋白酶的表达。相反，SIRT1 的激活通过关键自噬蛋白（Beclin1、ATG5、ATG7、LC3）上赖氨酸残基的脱乙酰化来增加软骨细胞的自噬。该激活被证明与 mTOR/ULK1 无关。我们的结果表明，SIRT1 维持软骨细胞自噬对于维持终生软骨完整性至关重要，因此是预防 OA 的药物干预的目标。