Biomechanical Loading as a Driver of Synovial Neovascularization and Microvascular Dysfunction in Knee Osteoarthritis
Abstract
Synovial inflammation and biomechanical loading are independent risk factors for knee osteoarthritis (OA). However, the relationship between inflammatory and biomechanical factors, specifically if increased biomechanical loading causes synovial inflammation in OA (mechanoinflammation), is not well understood. The purpose of this thesis was to explore the associations of knee load during walking with features of synovial inflammation in knee OA. The knee adduction moment magnitude was associated with increased synovial vascularization and perivascular edema. Synovial fluid from OA patients with high knee adduction moments promoted endothelial cell migration in vitro. Late-stage knee OA synovial fluid caused endothelial monolayer hyperpermeability in vitro regardless of the patient’s knee adduction moment magnitude. We identified placental growth factor as a synovial fluid cytokine associated with increased knee adduction moment magnitude. Our findings support the mechanoinflammatory hypothesis of knee OA and suggest that increased knee loading contributes to synovial microvascular dysfunction in knee OA.