Extracellular matrix remodeling in the pathogenesis and therapeutic strategies of rheumatoid arthritis

The pathological process of rheumatoid arthritis is not only driven by immune inflammation but is more profoundly shaped by abnormal remodeling of the extracellular matrix. This study systematically reviews the core manifestations of abnormal extracellular matrix remodeling in RA: matrix sclerosis, excessive degradation mediated by matrix metalloproteinase/a disintegrin and metalloproteinase with thrombospondin motifs, and degradation fragments as damage-associated molecular patterns activating the TLR4/RAGE pathway, thereby forming a self-perpetuating vicious cycle of "sclerosis-degradation-inflammation amplification-resclerosis," significantly exacerbating inflammatory reactions and joint damage. It proposes a dual framework of "mechanism loop-clinical loop," emphasizing the integration of the biomarkers C1M, C3M, COMP, HA, and other ECM-degradation fragments for dynamic disease monitoring, progression prediction, and precise efficacy evaluation. By combining biomarker panels with imaging data, it is expected to optimize the stratification of high-risk populations and individualized treatment adjustments, which may enhance the precision of diagnostic and therapeutic strategies and provide a new direction for RA to progress from inflammation control to structural protection.