Objective: Osteoarthritis (OA) is a degenerative rheumatic disease that is associated with extracellular matrix degradation and chondrocyte apoptosis in the articular cartilage. The role of mitochondria in degenerative diseases is widely recognized. We undertook this study to evaluate mitochondrial function in normal and OA chondrocytes and to examine age‐related changes in mitochondria.Methods: Mitochondrial function was evaluated by analyzing respiratory chain enzyme complexes and citrate synthase (CS) activities as well as changes in mitochondrial membrane potential (ΔΨm). The activities of mitochondrial respiratory chain complexes (complex I: rotenone‐sensitive NADH–coenzyme Q₁ reductase; complex II: succinate dehydrogenase; complex III: antimycin‐sensitive ubiquinol cytochrome c reductase; and complex IV: cytochrome c oxidase) and CS were measured in human articular chondrocytes isolated from OA and normal cartilage. ΔΨm was measured by JC‐1 using flow cytometry. Statistical analysis was performed using the Mann‐Whitney U test and Student's t‐test as well as several models of multiple linear regression.Results: OA articular chondrocytes had reduced activities of complexes II and III compared with cells from normal cartilage. However, the mitochondrial mass was increased in OA. Cultures of OA chondrocytes contained a higher proportion of cells with de‐energized mitochondria. We found no relationship between mitochondrial function and donor age either in normal or in OA chondrocytes.Conclusion: These findings suggest the involvement of mitochondrial function in the pathophysiology of OA. Cartilage degradation by OA and cartilage aging may be two different processes.

Objective: Alterations in mitochondria play a key role in the pathogenesis of osteoarthritis (OA). The role of inflammation in the progression of OA has also acquired important new dimensions. This study was undertaken to evaluate the potential role of mitochondrial dysfunction in increasing the inflammatory response of normal human chondrocytes to cytokines.Methods: Mitochondrial dysfunction was induced by commonly used inhibitors. Interleukin‐1β (IL‐1β) and tumor necrosis factor α (TNFα) were used as inflammatory mediators. IL‐8 and cyclooxygenase 2 (COX‐2) protein and messenger RNA (mRNA) expression and prostaglandin E₂ (PGE₂) levels were assessed. The chemotactic activity of neutrophils was assayed. Additionally, inhibitors of reactive oxygen species (ROS) and NF‐κB were used to identify possible inflammatory response pathways induced by mitochondrial dysfunction, and the effects of the natural antioxidant resveratrol were tested.Results: Pretreatment with antimycin A or oligomycin (inhibitors of mitochondrial respiratory chain complexes III and V, respectively) triggered a strong potentiation of IL‐1β–induced IL‐8 mRNA and protein expression (mean ± SEM at 18 hours 5,932 ± 1,995 pg/50,000 cells for IL‐1β alone versus 16,241 ± 5,843 pg/50,000 cells for antimycin A plus IL‐1β and 20,087 ± 5,407 pg/50,000 cells for oligomycin plus IL‐1β; P < 0.05). Similar results were observed with TNFα or when expression of the inflammatory mediator COX‐2 or PGE₂ production was assessed. Mitochondrial dysfunction increased the chemotactic activity induced by cytokines, and ROS and NF‐κB inhibitors decreased the production of IL‐8. Resveratrol significantly reduced the inflammatory response.Conclusion: Our findings indicate that mitochondrial dysfunction could amplify the responsiveness to cytokine‐induced chondrocyte inflammation through ROS production and NF‐κB activation. This pathway might lead to the impairment of cartilage and joint function in OA.