Poznyak Anastasia V, Orekhov Nikolay A, Churov Alexey V, Starodubtseva Irina Alexandrovna, Kovyanova Tatiana Ivanovna, Pecherina Tamara Borzalievna, Sukhorukov Vasily N, Orekhov Alexander N
Institute for Atherosclerosis Research, Osennyaya 4-1-207, 121609, Moscow, Russia.
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiiskaya Street, Moscow, 125315, Russia.
Curr Pharm Des. 2025 Apr 30. doi: 10.2174/0113816128354572250408165158.
This review explores the critical role of mitochondria in the immunometabolic processes underlying rheumatoid arthritis (RA) and osteoarthritis (OA). It examines the interplay between immune cells, metabolic demands, and tissue environments, emphasizing the impact of bioenergetics on immune responses and disease progression. Mitochondrial dysfunction in chondrocytes and immune cells contributes to OA and RA through mechanisms such as oxidative stress, disrupted calcium homeostasis, and inflammasome activation. In OA, mitochondrial dysfunction in chondrocytes results in impaired energy production, elevated reactive oxygen species (ROS), and calcium imbalance, leading to cartilage degradation and inflammation. The review highlights how disturbances in the mitochondrial respiratory chain and apoptotic pathways drive joint tissue damage. In contrast, RA shows how mitochondrial dysfunction influences chronic inflammation and synovial hyperplasia. The role of mitochondrial DNA (mtDNA) as a damage-associated molecular pattern (DAMP) is emphasized, illustrating how oxidized mtDNA activates inflammatory pathways, triggers immune responses, and contributes to joint destruction. Additionally, mitochondrial genetic variations may exacerbate inflammation and oxidative stress in RA. The review also discusses the effects of various RA treatments-conventional synthetic anti-rheumatic drugs, biological agents, and targeted synthetic DMARDs-on mitochondrial function. Insights into how these therapies modulate mitochondrial pathways and oxidative stress in immune and joint cells highlight new potential treatment strategies. This review enhances our understanding of OA and RA pathophysiology by elucidating the connections between mitochondria, immune responses, and rheumatic diseases, paving the way for innovative therapies targeting mitochondrial dysfunction.
本综述探讨了线粒体在类风湿关节炎（RA）和骨关节炎（OA）潜在免疫代谢过程中的关键作用。它研究了免疫细胞、代谢需求和组织环境之间的相互作用，强调了生物能量学对免疫反应和疾病进展的影响。软骨细胞和免疫细胞中的线粒体功能障碍通过氧化应激、钙稳态破坏和炎性小体激活等机制导致OA和RA。在OA中，软骨细胞的线粒体功能障碍导致能量产生受损、活性氧（ROS）升高和钙失衡，从而导致软骨降解和炎症。该综述强调了线粒体呼吸链和凋亡途径的紊乱如何驱动关节组织损伤。相比之下，RA展示了线粒体功能障碍如何影响慢性炎症和滑膜增生。强调了线粒体DNA（mtDNA）作为一种损伤相关分子模式（DAMP）的作用，说明了氧化的mtDNA如何激活炎症途径、触发免疫反应并导致关节破坏。此外，线粒体基因变异可能会加剧RA中的炎症和氧化应激。该综述还讨论了各种RA治疗方法——传统合成抗风湿药物、生物制剂和靶向合成DMARDs——对线粒体功能的影响。对这些疗法如何调节免疫和关节细胞中线粒体途径和氧化应激的见解突出了新的潜在治疗策略。本综述通过阐明线粒体、免疫反应和风湿性疾病之间的联系，增强了我们对OA和RA病理生理学的理解，为针对线粒体功能障碍的创新疗法铺平了道路。
