Mechanisms of matrix degradation in rheumatoid arthritis.

In the inflammatory synovium production of collagenase is probably responsible for the degradation of collagen in the extracellular matrix and distortion of the architecture and function of the joints. Major collagenase-producing cells are mesenchymal cells such as fibroblasts and chondrocytes, which synthesize and secrete the enzyme influenced by the action of cytokines produced by adjacent mononuclear cells. The cytokines act primarily through cell-surface receptors, whose signal is probably then mediated by complexes of nuclear oncoproteins, to activate transcription of the procollagenase gene. The increased production of collagenase ultimately is the result of a cascade of cellular effects involving complex interactions of different ligands in a system characterized by amplification and feedback loops.