THE LEVELS OF COLLAGENASE, TISSUE INHIBITOR OF METALLOPROTEINASES-1 (TIMP-1), COLLAGENASE-TIMP-1 COMPLEXES AND GLYCOSAMINOGLYCAN (GAG) IN SEQUENTIAL SAMPLES OF SYNOVIAL-FLUID ASPIRATED FROM PATIENTS WITH OSTEOARTHRITIS

Objective. Collagen turnover in connective tissues is thought to be co ntrolled by the balance between the levels of interstitial collagenase and tissue inhibitor of metalloproteinases (TIMP-1). The aim of this study was to measure the level of total collagenase (MMP-1), TIMP-1, c ollagenase similar to TIMP-1 complex and glycosaminoglycan (GAG) in se quential samples of osteoarthritic knee synovial fluid from well docum ented patients to determine if these parameters changed with time and correlated with clinical indices. Methods. Twenty-one patients were re cruited and randomly allocated to receive tiaprofenic acid, indomethac in or naproxen. Total collagenase, TIMP-1, collagenase similar to TIMP -1 complex and GAG were measured in 80 osteoarthritic synovial fluids taken over a period of six months. Results. The majority of fluids con tained a molar excess of TIMP-1 over collagenase, although in seven fl uids collagenase was present in excess; six of these samples were from a single patient. GAG levels were relatively unchanged over the six m onths studied. Conclusion. The levels of collagenase and TIMP-1 varied between patients and over time in individual patients. No collagenase similar to TIMP-1 complex was found in any fluid. There was no signif icant difference in the median levels of collagenase, TIMP-1 or GAG in the different treatment groups. High levels of collagenase were found in one patient with a crystal related disease. These immunoassays giv e valuable information on the levels of collagenase and TIMP-1 in indi vidual patients with time and may help to determine the mechanisms con trolling the turnover of cartilage collagen in different arthritides.