Tumor necrosis factor alpha can contribute to focal loss of cartilage in osteoarthritis.
Autor: | Westacott CI; Department of Pathology and Microbiology, University of Bristol, Bristol, U.K. carole.westacott@bristol.ac.uk, Barakat AF, Wood L, Perry MJ, Neison P, Bisbinas I, Armstrong L, Millar AB, Elson CJ |
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Jazyk: | angličtina |
Zdroj: | Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2000 May; Vol. 8 (3), pp. 213-21. |
DOI: | 10.1053/joca.1999.0292 |
Abstrakt: | Unlabelled: OBJECTIVE; To evaluate the potential for tumor necrosis factor alpha (TNFalpha)-induced focal loss of cartilage in osteoarthritic (OA) knee joints. Design: Fresh cartilage from specified regions of OA joints was immunostained for TNF-receptor (R) bearing chondrocytes. Cartilage explants from the same regions were cultured with or without small amounts of TNFalpha and cumulative GAG release into supernatants measured. Concentrations of TNFalpha, p55 and p75 soluble (s) TNF-R in supernatants from cultured OA and non-arthritic (NA) synovium were measured by ELISA. Results: TNF-R bearing chondrocytes were identified in OA cartilage; more specimens contained p55 TNF-R- than p75 TNF-R-bearing chondrocytes and differences in TNF-R distribution were apparent in cartilage from different regions of the same knees. TNFalpha at 5, 1, 0.5 and 0.25 ng/ml (but not 0.1 ng/ml) significantly increased glycosaminoglycans (GAG) release from cartilage explants in a dose-dependent manner. Variation in susceptibility to TNFalpha was observed in explants from different sites. TNFalpha and p75 sTNF-R, but not p55 sTNF-R, concentrations were significantly higher in OA, as compared with NA, supernatants. A significant correlation between TNFalpha and p75 sTNF-R measurements was apparent only in NA supernatants. Conclusions: Variations in chondrocyte TNF-R expression occur in OA cartilage in vivo. TNFalpha at concentrations produced by OA synovium in vitro, can degrade cartilage matrix. In most OA supernatants sTNF-R concentrations were insufficient to abrogate the effects of TNFalpha. Thus conditions exist in some OA knees for TNFalpha to contribute to focal loss of cartilage. |
Databáze: | MEDLINE |
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