Cartilage destruction by matrix degradation products

The progressive destruction of articular cartilage is one of the hallmarks of osteoarthritis and rheumatoid arthritis. Cartilage degradation is attributed to different classes of catabolic factors, including proinflammatory cytokines, aggrecanases, matrix metalloproteinases, and nitric oxide. Recently, matrix degradation products generated by excessive proteolysis in arthritis have been found to mediate cartilage destruction. These proteolytic fragments activate chondrocytes and synovial fibroblasts via specific cell surface receptors that can stimulate catabolic intracellular signaling pathways, leading to the induction of such catalysts. This review describes the catabolic activities of matrix degradation products, especially fibronectin fragments, and discusses the pathologic implication in cartilage destruction in osteoarthritis and rheumatoid arthritis. Increased levels of these degradation products, found in diseased joints, may stimulate cartilage breakdown by mechanisms of the kind demonstrated in the review.