Figure 1.

Arthritic joint changes and the pathogenic role of protease-activated receptor-2 (PAR2). (A) Schematic representation of a normal healthy joint, highlighting the various joint tissues, cell types residing within, and the expression of PAR2 in the healthy joint. (B) A schematic representation of a rheumatoid arthritis-affected joint, highlighting characteristic changes including: synovitis, degradation of the articular cartilage; bone erosion and increased inflammatory factors. PAR2 expression is also highlighted in pathogenic areas known to be influenced by PAR2 from animal studies or in vitro cell work. Including, increase in PAR2 expression in monocytes, macrophages, and fibroblast-like synoviocytes, and contributing to monocyte IL-6 production, macrophage cytokine production, autoantibody production, bone erosion, and cartilage destruction. (C) Schematic representation of an osteoarthritis (OA)-affected joint, highlighting characteristic changes including: synovitis; degradation of the articular cartilage; osteophyte formation; subchondral bone sclerosis and pannus formation. PAR2 expression is also highlighted in cells/tissues and pathogenic outcomes known to be influenced by PAR2 from animal studies or in vitro cell work. Increased levels of PAR2 have been found in OA chondrocytes, fibroblasts, and macrophages, with PAR2 known to play a role in osteophyte formation, cartilage degradation (through catabolic protease production), and inflammation.