Ma Yiyang, Pang Yidan, Cao Ruomu, Zheng Zhikai, Zheng Kaiwen, Tian Yucheng, Peng Xiaoyuan, Liu Delin, Du Dajiang, Du Lin, Zhong Zhigang, Yao Lufeng, Zhang Changqing, Gao Junjie
Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
iScience. 2024 Jul 27;27(9):110597. doi: 10.1016/j.isci.2024.110597. eCollection 2024 Sep 20.
Articular cartilage degeneration may lead to osteoarthritis (OA) during the aging process, but its underlying mechanism remains unknown. Here, we found that chondrocytes exhibited an energy metabolism shift from glycolysis to oxidative phosphorylation (OXPHOS) during aging. Parkin regulates various cellular metabolic processes. Reprogrammed cartilage metabolism by Parkin ablation decreased OXPHOS and increased glycolysis, with ameliorated aging-related OA. Metabolomics analysis indicated that lauroyl-L-carnitine (LLC) was decreased in aged cartilage, but increased in Parkin-deficient cartilage. , LLC improved the cartilage matrix synthesis of aged chondrocytes. , intra-articular injection of LLC in mice with anterior cruciate ligament transaction (ACLT) ameliorated OA progression. These results suggest that metabolic changes are regulated by Parkin-impaired cartilage during aging, and targeting this metabolomic changes by supplementation with LLC is a promising treatment strategy for ameliorating OA.
关节软骨退变在衰老过程中可能导致骨关节炎（OA），但其潜在机制仍不清楚。在此，我们发现软骨细胞在衰老过程中表现出能量代谢从糖酵解向氧化磷酸化（OXPHOS）的转变。帕金蛋白调节各种细胞代谢过程。通过敲除帕金蛋白重新编程的软骨代谢降低了氧化磷酸化并增加了糖酵解，改善了与衰老相关的骨关节炎。代谢组学分析表明，月桂酰-L-肉碱（LLC）在老化软骨中减少，但在帕金蛋白缺陷的软骨中增加。LLC改善了老化软骨细胞的软骨基质合成。关节内注射LLC可改善前交叉韧带横断（ACLT）小鼠的骨关节炎进展。这些结果表明，衰老过程中代谢变化受帕金蛋白损伤的软骨调节，通过补充LLC靶向这种代谢组学变化是改善骨关节炎的一种有前景的治疗策略。
