Cartilage damage by matrix degradation products: fibronectin fragments.

Catabolic cytokines play a major role in cartilage degradation not only in rheumatoid arthritis but also in osteoarthritis. Although the major source in rheumatoid arthritis may be mononuclear cells and synovial tissue and the cause of release may be multifactorial, the source of cytokines in osteoarthritis would be mostly from chondrocytes. However, there are few explanations of how upregulation of the cytokines might occur in osteoarthritis. One possibility is that degradation products of the extracellular matrix arising from elevated protease levels, substrate, or both, might regulate cytokine activities. Fragments of the extracellular matrix protein, fibronectin, upregulate cytokine expression and induce the events of suppressed matrix synthesis and upregulation of matrix metalloproteinases, characteristic of osteoarthritis. The catabolic aspects of this system are short term, subsequently serve to enhance anabolic processes above untreated levels, and condition the tissue against additional insult. It will be necessary to determine whether in vivo these degradation products precede cytokine expression and act early and are targets for intervention or instead are a consequence of cytokine damage. Whether they regulate anabolism and catabolism, blocking of their activities may not be ideal.