Tan Siyuan, Sun Yujun, Li Shixun, Wu Haoyu, Ding Yue
Department of Orthopedic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Bone Res. 2025 Sep 1;13(1):77. doi: 10.1038/s41413-025-00460-x.
Osteoarthritis (OA) is a degenerative joint disease associated with age, prominently marked by articular cartilage degradation. In OA cartilage, the pathological manifestations show elevated chondrocyte hypertrophy and apoptosis. The mitochondrion serves as key energy supporter in eukaryotic cells and is tightly linked to a myriad of diseases including OA. As age advances, mitochondrial function declines progressively, which leads to an imbalance in chondrocyte energy homeostasis, partially initiating the process of cartilage degeneration. Elevated oxidative stress, impaired mitophagy and mitochondrial dynamics jointly contribute to chondrocyte pathology, with mitochondrial DNA haplogroups, particularly haplogroup J, influencing OA progression. Therapeutic approaches directed at mitochondria have demonstrated remarkable efficacy in treating various diseases, with triphenylphosphonium (TPP) emerging as the most widely utilized molecule. Other strategies encompass Dequalinium (DQA), the Szeto-Schiller (SS) tetrapeptide family, the KLA peptide, and mitochondrial-penetrating peptides (MPP), etc. These molecules share common properties of lipophilicity and positive charge. Through various technological modifications, they are conjugated to nanocarriers, enabling targeted drug delivery to mitochondria. Therapeutic interventions targeting mitochondria offer a hopeful direction for OA treatment. In the future, mitochondria-targeted therapy is anticipated to improve the well-being of life for the majority of OA patients. This review summarizes the link between chondrocyte mitochondrial dysfunction and OA, as well as discusses promising mitochondria-targeted therapies and potential therapeutic compounds.
骨关节炎（OA）是一种与年龄相关的退行性关节疾病，其显著特征是关节软骨退化。在OA软骨中，病理表现为软骨细胞肥大和凋亡增加。线粒体是真核细胞中的关键能量支持者，与包括OA在内的多种疾病密切相关。随着年龄的增长，线粒体功能逐渐下降，导致软骨细胞能量稳态失衡，部分引发软骨退变过程。氧化应激增加、线粒体自噬受损和线粒体动力学共同导致软骨细胞病变，线粒体DNA单倍群，特别是单倍群J，影响OA的进展。针对线粒体的治疗方法在治疗各种疾病方面已显示出显著疗效，三苯基膦（TPP）成为应用最广泛的分子。其他策略包括地喹氯铵（DQA）、泽托-席勒（SS）四肽家族、KLA肽和线粒体穿透肽（MPP）等。这些分子具有亲脂性和正电荷的共同特性。通过各种技术修饰，它们与纳米载体偶联，实现线粒体靶向药物递送。针对线粒体的治疗干预为OA治疗提供了一个有希望的方向。未来，线粒体靶向治疗有望改善大多数OA患者的生活质量。本综述总结了软骨细胞线粒体功能障碍与OA之间的联系，并讨论了有前景的线粒体靶向治疗和潜在的治疗化合物。
