Impaired Efferocytosis in Knee Osteoarthritis
Abstract
Non-resolving synovial inflammation is present in both human and animal models and plays a key role in the pathogenesis of knee osteoarthritis (OA). However, it is not known how inflammation affects synovial macrophage function and if this contributes to the loss of tissue homeostasis. The purpose of this thesis was to understand the role of efferocytosis in knee OA. There is an increased apoptotic cell burden within the synovium of patients with late-stage knee OA. Synovial-derived macrophages from these patients exhibited impaired efferocytosis. Healthy blood-derived macrophages exposed to synovial fluid from patients with knee OA recapitulated the defective efferocytosis. Impaired efferocytosis in a rat model of post-traumatic knee OA was associated with increased pain-related behaviours, joint damage, and synovial apoptotic cell burden. Our findings support the key functions of the synovium and emphasizes the importance of targeting synovial health in OA to improve outcomes.