Advances in research of neutrophil extracellular trap formation in osteoarticular diseases

Figure 4 Schematic representation of the role of neutrophil elastase in synovial cartilage integrity in rheumatoid arthritis. 1: Neutrophils in rheumatoid synovium exhibit dysregulated NETosis; 2: Neutrophil-derived elastase within neutrophil extracellular traps degrades cartilage matrix, producing immunogenic fragments; 3: Membrane-bound peptidyl arginine deiminase 2 is liberated from fibroblast-like synoviocytes (FLSs) through elastase-mediated cleavage; 4: The liberated peptidyl arginine deiminases 2 catalyzes citrullination of cartilage fragments, which are subsequently internalized by FLSs; 5: FLSs present these citrullinated peptides to autoreactive CD4⁺ T cells; 6: Triggering B cell differentiation and production of autoantibodies targeting citrullinated proteoglycans; 7: The resulting immune complexes stimulate macrophage activation and secretion of proinflammatory mediators; 8: These cytokines further prime neutrophils for elastase release, establishing a self-amplifying inflammatory cascade that perpetuates cartilage destruction. Created by Figdraw, ID: TAASU77e88. NETs: Neutrophil extracellular traps; IL: Interleukin; TNF: Tumor necrosis factor; MMP: Matrix metalloproteinase.