Research Progress on the Relationship between Joint Immune Microenvironment and Osteoarthritis Progression

Abstract

Osteoarthritis (OA) has conventionally been considered a degenerative mechanical condition; but an increasing number of studies support an alternative perception of this disease as one characterized by impaired immune homeostasis in the joint environment. The purpose of this review is to analyze the mechanisms of how the synovium, cartilage, subchondral bone, and infrapatellar fat pad operate as one interconnected immune system where 60-70% of all synovial immune cells represent resident macrophages. There are four fundamental elements of this condition’s pathogenesis: M1/M2 imbalance that leads to the progressive reduction in the number of M2 cells; Th17/Treg dysregulation promoting MMP-3 and MMP-13 up-regulation; cytokine networks, which include IL-1β and TNF-α and trigger degradation of the cartilage matrix; and activation of the inflammasome due to release of DAMPs that creates a perpetual inflammation cycle. Metabolic disorders, cellular senescence, mechanical overload (Piezo1 signaling), and the disruption of the gut-joint connection represent additional regulatory factors contributing to the above-mentioned processes.