Osteoarthritis (OA) is a complex joint disease that currently has no cure. OA involves metabolic disorders in chondrocytes and an imbalance between autophagy and apoptosis. As a common risk factor for OA, obesity induces changes in the fatty acid composition of synovial fluid, thereby disturbing chondrocyte homeostasis. However, whether unsaturated fatty acids affect the development of OA by regulating chondrocyte autophagy remains unclear. This study aimed to determine the effects of oleic and linoleic acids on chondrocyte autophagy and related mechanisms. Based on the mass spectrometry results, the levels of multiple unsaturated fatty acids, including oleic and linoleic acids, in the synovial fluid of patients with OA and obesity were significantly higher than those in patients with OA only. Moreover, we found that FOXO1 and SIRT1 were downregulated after oleic and linoleic acids treatment of chondrocytes, which inhibited chondrocyte autophagy. Importantly, the upregulation of SIRT1 and FOXO1 expression not only increased the level of autophagy but also improved the expression of chondrocyte extracellular matrix proteins. Furthermore, upregulated SIRT1 and FOXO1 expression alleviated the destruction of the articular cartilage in an OA rat model. Our results suggest that SIRT1/FOXO1 signaling can alleviate oleic acid- and linoleic acid-induced cartilage degradation both and and that the SIRT1/FOXO1 pathway may serve as an effective treatment target for inhibiting OA progression.

中文翻译：

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油酸和亚油酸通过下调 SIRT1/FOXO1 信号传导抑制自噬，从而促进软骨细胞凋亡

骨关节炎（OA）是一种复杂的关节疾病，目前尚无法治愈。OA涉及软骨细胞的代谢紊乱以及自噬和凋亡之间的不平衡。作为骨关节炎的常见危险因素，肥胖会引起滑液脂肪酸组成的变化，从而扰乱软骨细胞的稳态。然而，不饱和脂肪酸是否通过调节软骨细胞自噬影响OA的发生仍不清楚。本研究旨在确定油酸和亚油酸对软骨细胞自噬的影响及相关机制。根据质谱分析结果，OA合并肥胖患者滑液中多种不饱和脂肪酸（包括油酸和亚油酸）的水平显着高于单纯OA患者。此外，我们发现油酸和亚油酸处理软骨细胞后，FOXO1和SIRT1表达下调，从而抑制软骨细胞自噬。重要的是，SIRT1和FOXO1表达的上调不仅增加了自噬水平，而且还提高了软骨细胞胞外基质蛋白的表达。此外，上调 SIRT1 和 FOXO1 表达可减轻 OA 大鼠模型中关节软骨的破坏。我们的结果表明，SIRT1/FOXO1 信号传导可以减轻油酸和亚油酸诱导的软骨退化，并且 SIRT1/FOXO1 通路可能作为抑制 OA 进展的有效治疗靶点。