IMMUNOLOCALIZATION STUDIES ON 6 MATRIX METALLOPROTEINASES AND THEIR INHIBITORS, TIMP-1 AND TIMP-2, IN SYNOVIA FROM PATIENTS WITH OSTEOARTHRITIS AND RHEUMATOID-ARTHRITIS

Objective-To assess the likely importance of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the arthritic process. Methods -Synovial samples from seven joints with rheumatoid arthritis and thre e osteoarthritic joints were analysed by indirect immunofluorescence m icroscopy. Using specific human antisera, we documented the frequencie s and distributions of collagenase, stromelysins 1 and 2, matrilysin, gelatinases A and B, TIMP-1, and TIMP-2. Results-Stromelysin 1 was fou nd in all synovia, bound to extracellular matrix, within cells, or bot h, indicating stromelysin synthesis. Matrilysin was present in only on e active inflammatory synovium, and focal synthesis of collagenase and gelatinase A was seen in four synovia. Stromelysin and TIMP-2 were no t observed, but TIMP-1 synthesis was seen in five synovia, and in two active synovia the distribution of TIMP-1 positive cells was more wide spread than that of MMPs. Conclusions-The presence of stromelysin 1 al l synovia clearly implicates enzyme Collagenase, gelatinase A and matr ilysin may also have a role in rheumatoid arthritis, but are not signi ficant in osteoarthritis. However, marked regional variations were fou nd in the synthesis of these MMPs, indicating not only that these dise ases are episodic but that control of enzyme synthesis is focal. Only TIMP-1 may be considered an inhibitory factor.