Quantitation of metalloproteinase gene expression in rheumatoid and psoriatic arthritis synovial tissue distal and proximal to the cartilage-pannus junction

OBJECTIVE: The distinct and different patterns of radiological damage in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) may be a product of the relative balance of proteolytic enzyme and inhibitor gene expression in synovial tissue. This study compared metalloproteinase gene expression in synovium located proximal to the cartilage-pannus junction (CPJ) and distal to the CPJ (non-CPJ) in patients with PsA and RA. 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.