Synovial Macrophage Mitochondrial Dysfunction in Knee Osteoarthritis
Abstract
In knee osteoarthritis (OA), chronic synovial inflammation (synovitis) plays a key role in disease pathogenesis and is associated with patient symptom severity. However, it is not known how inflammation affects synovial macrophage function and whether mitochondrial impairment in synovial macrophages contributes to synovitis and pain. The purpose of this thesis was to examine the impact of the OA joint environment on macrophage mitochondria and to explore associations between synovial macrophage mitochondrial function and disease activity in knee OA. Synovial-derived macrophages from late-stage knee OA patients with severe pain and inflammation exhibited transcriptomic and morphological features indicative of mitochondrial stress. Healthy blood-derived macrophages exposed to synovial fluids from OA patients showed oxidative stress responses and altered mitochondrial morphology/activity, regardless of disease severity. Treatment with mitochondria-protective drugs mitigated oxidative damage in OA-exposed macrophages. Our findings highlight the importance of mitochondrial function in the synovium and suggest that mitochondrial dysfunction in synovial macrophages may perpetuate pain and inflammation in OA.