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Quantitation of Metalloproteinase Gene Expression in Rheumatoid and Psoriatic Arthritis Synovial Tissue Distal and Proximal to the Cartilage-Pannus Junction
DAVID KANE, LISELOTTE E. JENSEN, SHARON GREHAN, ALEXANDER S. WHITEHEAD, BARRY BRESNIHAN, and OLIVER FITZGERALD
ABSTRACT.
Methods. Synovial biopsies were obtained from CPJ and non-CPJ sites under direct vision at arthroscopy of an inflamed knee in patients with PsA (n = 12) and RA (n = 12) who were not under disease modifying antirheumatic drug treatment. A competitive, quantitative RT-PCR technique was established for synovial RNA using a polycompetitor construct containing mRNA-specific primer sites for collagenase (MMP-1), stromelysin (MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1), and GAPDH. cDNA products were separated and quantified by ethidium bromide stained gel electrophoresis and mRNA values were normalized relative to GAPDH expression. Results. MMP-1, MMP-3, and TIMP-1 mRNA were upregulated in RA and PsA synovium with a prodestructive (MMP-1 + MMP-3)/TIMP-1 balance in both diseases. Similar levels of MMP mRNA expression were observed in PsA and RA despite the presence of less radiological erosion in the PsA group. No difference was observed in the degree of upregulation of MMP-1, MMP-3, or TIMP-1 mRNA in paired biopsies from CPJ and non-CPJ sites in either PsA (n = 8) or RA (n = 10). The ratio of TIMP-1 expression in CPJ compared to non-CPJ biopsies was higher in patients with nonerosive disease (10.1 ± 27.8) than in erosive patients (0.75 ± 0.27; p = 0.07). Conclusion. PsA and RA have similar levels of MMP-1, MMP-3, and TIMP-1 mRNA expression in synovium. There is no evidence of increased metalloproteinase mRNA expression at the CPJ in RA or PsA. The different patterns of radiological progression seen in RA and PsA were not explained by differences in synovial mRNA expression of MMP-1, MMP-3, or TIMP-1. (J Rheumatol 2004; 31:1274-80) Key Indexing Terms:
METALLOPROTEINASE
From the Department of Rheumatology, St. Vincent's University Hospital, Dublin, Ireland; the Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA; and the Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA. D. Kane, PhD, MRCPI; B. Bresnihan, MD, FRCPI, FRCP; O. FitzGerald, MD, FRCPI, FRCP, St. Vincent's University Hospital; L.E. Jensen, PhD; A.S. Whitehead, DPhil, University of Pennsylvania School of Medicine; S. Grehan, PhD, Gladstone Institute of Cardiovascular Disease. Address reprint requests to Prof. O. FitzGerald, Department of Rheumatology, St. Vincent's University Hospital, Dublin 4, Ireland. E-mail: ofitzger@iol.ie Submitted April 29, 2003; revision accepted January 12, 2004. |