Wu Yubin, Hou Mingzhuang, Deng Yaoge, Xia Xiaowei, Liu Yang, Yu Jianfeng, Yu Chenqi, Yang Huilin, Zhang Yijian, Zhu Xuesong
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215000, China.
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215000, China.
Redox Biol. 2025 Apr;81:103535. doi: 10.1016/j.redox.2025.103535. Epub 2025 Feb 7.
Conventional pharmacotherapy exhibits limited efficacy in halting cartilage degeneration, whereas exercise interventions have demonstrated promising protective effects against osteoarthritis (OA), albeit with unclear underlying mechanisms. This study investigated the beneficial effects of swimming in mitigating local joint damage through the enhancement of systemic antioxidant capacity. We found that overexpression of superoxide dismutase 3 (SOD3) could promote the elimination of extracellular reactive oxygen species (ROS) and preserve the cartilage extracellular matrix (C-ECM). Conversely, genetic deletion of SOD3 accelerated the loss of C-ECM and contributed to OA due to an imbalance in extracellular oxidative stress. Further investigation revealed that SOD3 could interact with CCAAT/enhancer binding protein β (C/EBPβ), leading to the inhibition of apolipoprotein E (APOE) transcription and subsequent APOE-induced cholesterol transport. Ultimately, we developed targeted extracellular vesicles (EVs) with high cartilage affinity for efficient and precise delivery of SOD3. Overall, this study elucidated the potential of exercise for degenerative joint disorders through SOD3-mediated extracellular antioxidation and cholesterol redistribution.
传统药物疗法在阻止软骨退变方面疗效有限，而运动干预已显示出对骨关节炎（OA）有前景的保护作用，尽管其潜在机制尚不清楚。本研究通过增强全身抗氧化能力，探讨游泳在减轻局部关节损伤方面的有益作用。我们发现超氧化物歧化酶3（SOD3）的过表达可促进细胞外活性氧（ROS）的清除并保留软骨细胞外基质（C-ECM）。相反，SOD3的基因缺失会加速C-ECM的丢失，并因细胞外氧化应激失衡而导致OA。进一步研究表明，SOD3可与CCAAT/增强子结合蛋白β（C/EBPβ）相互作用，导致载脂蛋白E（APOE）转录受抑制以及随后APOE诱导的胆固醇转运受抑制。最终，我们开发了具有高软骨亲和力的靶向细胞外囊泡（EVs），用于高效精确地递送SOD3。总体而言，本研究通过SOD3介导的细胞外抗氧化和胆固醇再分布，阐明了运动对退行性关节疾病的潜在作用。
