Elevated baseline levels of COMP and MIA might reflect increased joint matrix turnover and/or damage due to prior extreme physical training. During the run, COMP was increasing possibly due to the severe physical strain on joint structures, associated with the early inflammation. After the run, MIA and CRP increased within 24 h, suggesting a correlation with later inflammatory processes. Thus, our data suggest that COMP and MIA are markers for distinct aspects of joint metabolism and/or damage in both disease and sport.
Interstitial FGF-2 protein and mRNA expression correlate with interstitial scarring. FGF-2 is a strong mitogen for cortical kidney fibroblasts and may promote autocrine fibroblast growth. Expression of FGF-2 correlates with interstitial and tubular proliferation in vivo.
Objective. Sentrin, a novel antiapoptotic molecule, has been shown to interact with the signalcompetent form of Fas/APO-1 and tumor necrosis factor receptor I (TNFRI), and thereby, to protect cells against anti-Fas/APO-1-and TNF-induced cell death. Since reduced apoptosis in the synovial lining is supposed to contribute to synovial hyperplasia in rheumatoid arthritis (RA), we searched for the expression of sentrin-1 messenger RNA (mRNA) in synovium from patients with RA.Methods. The expression of sentrin-1 mRNA was examined by in situ hybridization on snap-frozen sections of normal and RA synovial tissues as well as on paraffin-embedded RA synovial specimens, including the interface of cartilage-bone and invading synovium. Immunohistochemical double labeling after in situ hybridization was performed to further characterize sentrin-1 mRNA-expressing cells. In addition, quantitative analysis of sentrin-1 mRNA expression in RA synovial fibroblasts (RASF), osteoarthritis synovial fibroblasts (OASF), and normal fibroblasts was performed by quantitative real-time polymerase chain reaction. Expression levels were standardized to the expression of GAPDH. The in vivo maintenance of sentrin expression in RASF aggressively invading human cartilage was explored in the SCID mouse model of RA.Results. A marked expression of sentrin-1 mRNA could be seen in all RA synovial specimens, predominantly in SF of the lining layer and at sites of invasion of RA synovium into cartilage. In normal synovial tissues, no sentrin-1 mRNA was detectable. RASF showed a maximum 32.5-fold (mean ؎ SD 14.9 ؎ 11.6) increase of sentrin-1 mRNA expression compared with normal fibroblasts and a maximum 31.4-fold (mean ؎ SD 14.3 ؎ 10.9) increase compared with OASF. When coimplanted with normal human cartilage in the SCID mouse model, invading RASF maintained their sentrin-1 mRNA expression for at least 60 days in vivo.
Conclusion. Similar to tissue-derived RA synovial fibroblasts, RA synovial fluid adherent cells, which contain "floating" anchorage-independent fibroblastlike cells, mediate cartilage destruction independent of the hyperplastic synovial tissue.
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