骨关节炎是临床上常见的慢性退行性疾病，软骨损伤的修复问题一直是研究热点。近年来，关于代谢物衣康酸的抗炎信号通路研究迅速占领国际最前沿。然而其在骨关节炎软骨损伤修复中的作用尚无研究。我们前期实验发现，衣康酸的衍生物4-辛基衣康酸（4-octyl itaconate，OI）可以降低脂多糖诱导的炎性损伤的软骨细胞内炎性因子的水平，并促进间充质干细胞向软骨细胞分化，提示我们OI很可能在修复炎性损伤的软骨中具有重要作用。本课题拟利用小鼠软骨细胞、间充质干细胞、小鼠炎症模型以及Nrf2基因敲除小鼠，在分子、细胞和动物水平开展系统的研究，以揭示OI在炎性损伤的软骨细胞中的抗炎作用，以及OI诱导间充质干细胞向软骨分化再生的作用，并阐明OI激活Nrf2信号通路在修复软骨损伤中的机制。相信本课题的研究成果，对解释软骨损伤修复机制具有重要的理论和临床价值，有潜力开发成新的治疗骨关节炎和诱导软骨再生的药物。

Osteoarthritis is a clinically common chronic degenerative disease. The repair of cartilage damage has always been a research hotspot. Recently, the research of anti-inflammatory signaling pathway of metabolite itaconate has quickly become forefront. However, its role in the repair of cartilage injury in osteoarthritis has not been studied. Previously, we proved that derivatives of itaconate 4-octyl itaconate (OI) could decrease the expression of inflammatory factors in lipopolysaccharide stimulated chondrocytes and promote the differentiation of mesenchymal stem cells into chondrocytes, suggesting that OI is likely to play an important role in repairing inflammatory cartilage. This research aims to systematically elucidate the role of OI in inhibiting inflammation in chondrocyte and inducing chondrogenic differentiation in mesenchymal stem cell, and further reveal the mechanism of Nrf2 signaling pathway in OI repairing injured cartilage, at the molecular, cellular and animal levels using mouse chondrocytes, mesenchymal stem cells, mouse inflammation models and Nrf2 knockout mice. This study will have important theoretical and clinical value for explaining the mechanism of cartilage injury repair, and have the potential to develop a new drug for anti-osteoarthritis and inducing cartilage regeneration.