Figure 3.

Summary of the major molecular and cellular changes that occur in the synovial joint during inflammation in OA. Summary of the major synovial, chondral and subchondral changes observed in OA. This schematic also highlights the actions of various white blood cells and inflammatory mediators in OA. Chondral changes include cartilage fragmentation (fibrillation), cartilage degradation and loss of collagen type II and glycosaminoglycans, chondrocyte apoptosis (hypocellularity) and matrix mineralization. Synovial membrane changes in OA include inflammation, synovial hypertrophy, recruitment and activation of T cells, macrophages and fibroblasts, production of matrix metalloproteinases (MMPs) and reactive oxygen species (ROS). Synovial fluid alterations in OA include accumulation of MMPs and ROS, release of IL-1β, TNF-α and other proinflammatory cytokines (IL-6, IL-8), release of inflammatory pain mediators such as prostaglandin E₂ (PGE₂), formation of degradative products and microcrystals. Subchondral alterations in OA include subchondral sclerosis (i.e., eburnation), osteoblast mediated subchondral bone formation, proteolysis (degradation) of IGF-I and IGF-I binding proteins, increased production of some growth factors and cytokines including: transforming growth factor β, TGF-β, PGE₂; interleukin 6, IL-6 and IGF-I.