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1.  In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis and rats with adjuvant and streptococcal cell wall arthritis. 
Cyclooxygenase (COX), or prostaglandin (PG) H synthase, plays a role in inflammatory diseases, but very limited data exist on the regulation of COX in vivo. We, therefore, studied the in vivo expression of COX in synovia from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), as well as joints of rats with streptococcal cell wall (SCW) and adjuvant arthritis. Extensive and intense intracellular COX immunostaining, which correlated with the extent and intensity of mononuclear cell infiltration, was observed in cells throughout RA synovia. Significantly less or equivocal staining was noted in OA and normal human synovia. Similarly, COX immunostaining was equivocal in the joints of normal and arthritis-resistant F344/N rats. In contrast, high level expression developed rapidly in euthymic female Lewis (LEW/N) rats throughout the hindlimb joints and overlying tissues including skin, preceding or paralleling clinically apparent experimental arthritis. COX was expressed in the joints of athymic LEW.rnu/rnu rats 2-4 d after injection of SCW or adjuvant but was not sustained. Physiological doses of antiinflammatory glucocorticoids, but not progesterone, suppressed both arthritis and COX expression in LEW/N rats. These observations suggest that, in vivo, (a) COX expression is upregulated in inflammatory joint diseases, (b) the level of expression is genetically controlled and is a biochemical correlate of disease severity, (c) sustained high level up-regulation is T cell dependent, and (d) expression is down-regulated by antiinflammatory glucocorticoids.
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PMCID: PMC442824  PMID: 1729286
2.  Transin/stromelysin expression in the synovium of rats with experimental erosive arthritis. In situ localization and kinetics of expression of the transformation-associated metalloproteinase in euthymic and athymic Lewis rats. 
Journal of Clinical Investigation  1989;84(6):1731-1740.
Transin is a neutral metalloproteinase initially isolated from malignantly transformed rat fibroblasts and subsequently shown to be homologous to human stromelysin. We performed Northern blot analysis on synovial tissue specimens from Lewis rats with proliferative and invasive streptococcal cell wall (SCW) arthritis. Transin mRNA was present in abundance, as was the mRNA of the c-myc oncogene, which is associated with cellular proliferation. Immunohistochemical staining of synovia from rats with chronic SCW arthritis showed high-level transin expression in the cells of the lining layer and underlying stroma, as well as in chondrocytes and osteoclasts in subchondral bone. Intense nuclear staining for the Myc oncoprotein was also detected with a cross-reactive antibody to v-Myc. Transin stained similarly in the early, rapid-onset, thymus-independent, acute phase of SCW arthritis. In the T cell-dependent adjuvant arthritis, transin expression was noted by day 4, 6 d before the influx of mononuclear cells and the onset of clinical disease. Athymic rats did not express transin. We concluded that transin is a marker of proliferative, invasive arthritis in rats and appears early in the course of disease development, but requires a competent immune system to sustain its expression in these model arthropathies.
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PMCID: PMC304049  PMID: 2687329

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