Plasminogen activators and their inhibitors in synovial fluids from normal, osteoarthritis, and rheumatoid arthritis knees.

C Belcher, F Fawthrop, R Bunning, M Doherty

Rheumatology Unit, City Hospital, Nottingham, United Kingdom.

OBJECTIVES: To establish baseline concentrations of plasminogen activators and their inhibitors in normal knee synovial fluids, and to compare them with well characterised osteoarthritis (OA) and rheumatoid arthritis (RA) knee fluids. METHODS: A total of 26 normal subjects, 71 patients with OA, and 17 patients with RA underwent knee aspiration. Patients with OA were subclassified according to presence of nodal generalised OA (NGOA) and synovial fluid calcium pyrophosphate crystals. Clinical assessment of inflammation (graded 0-6) was undertaken in OA and RA patients. Plasminogen activator (PA), plasminogen activator inhibitor (PAI), and urokinase-type PA receptor (uPAR) antigen concentrations were determined by enzyme linked immunosorbent assay. The species of PAs present were determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. RESULTS: Concentrations of all antigens (uPA, tissue-type PA (tPA), uPAR, and PAI-1), were significantly greater in RA than OA; those in OA were significantly greater than normal. The concentrations showed no direct association with clinically assessed inflammation of the knee. In normal fluids, no associations with age were observed. Antigen concentrations (uPA, tPA, and uPAR) in NGOA differed from those in other subclasses of OA, but the species of PA present did not appear to vary between disease groups. The predominant PA appeared to have identity with uPA. CONCLUSION: Because of the greater concentrations of these antigens in OA compared with normal fluids, OA cannot be used as a surrogate normal control in studies of the PA/PAI system. Alteration of the PA/PAI system was confirmed in RA and OA knee fluids, with greater changes evident in RA. The finding of different concentrations of PA antigens in NGOA compared with other OA fluids further supports a different pathogenic mechanism in this subset.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Jo, M., Takimoto, S., Montel, V., Gonias, S. L. (2009). The Urokinase Receptor Promotes Cancer Metastasis Independently of Urokinase-Type Plasminogen Activator in Mice. Am. J. Pathol. 175: 190-200 [Abstract] [Full Text]  
• Li, J., Ny, A., Leonardsson, G., Nandakumar, K. S., Holmdahl, R., Ny, T. (2005). The Plasminogen Activator/Plasmin System Is Essential for Development of the Joint Inflammatory Phase of Collagen Type II-Induced Arthritis. Am. J. Pathol. 166: 783-792 [Abstract] [Full Text]  
• Slot, O., Brünner, N., Locht, H., Oxholm, P., Stephens, R. W (1999). Soluble urokinase plasminogen activator receptor in plasma of patients with inflammatory rheumatic disorders: increased concentrations in rheumatoid arthritis. Ann Rheum Dis 58: 488-492 [Abstract] [Full Text]  
• BUSSO, N., SO, A. (1997). Urokinase in rheumatoid arthritis: causal or coincidental?. Ann Rheum Dis 56: 705-706 [Full Text]  
• CREAMER, P (1997). Intra-articular corticosteroid injections in osteoarthritis: do they work and if so, how?. Ann Rheum Dis 56: 634-635 [Full Text]  
• Busso, N., Péclat, V., So, A., Sappino, A.-P. (1997). Plasminogen activation in synovial tissues: differences between normal, osteoarthritis, and rheumatoid arthritis joints. Ann Rheum Dis 56: 550-557 [Abstract] [Full Text]  
• Belcher, C., Yaqub, R., Fawthrop, F., Bayliss, M., Doherty, M. (1997). Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in arthritic and normal knees. Ann Rheum Dis 56: 299-307 [Abstract] [Full Text]