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image of Connection Between Mitochondria and Rheumatoid Arthritis and Osteoarthritis: Personalized Treatment Strategies

Abstract

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.

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2025-04-30
2025-09-10

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Connection Between Mitochondria and Rheumatoid Arthritis and Osteoarthritis: Personalized Treatment Strategies
Bentham Science Publishers ; https://doi.org/10.2174/0113816128354572250408165158
/content/journals/cpd/10.2174/0113816128354572250408165158
/content/journals/cpd/10.2174/0113816128354572250408165158
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  • Article Type:     Review Article
Keywords: immune response ; Osteoarthritis ; rheumatic diseases ; autoimmunity ; inflammation ; rheumatoid arthritis

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