Journal
OSTEOARTHRITIS AND CARTILAGE
Volume 8, Issue 3, Pages 213-221Publisher
W B SAUNDERS CO LTD
DOI: 10.1053/joca.1999.0292
Keywords
osteoarthritis; cartilage; tumor necrosis factor-alpha (TNF alpha); soluble tumor necrosis factor-receptors (sTNF-R)
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Objective: To evaluate the potential for tumor necrosis factor alpha (TNF alpha)-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 TNF alpha and cumulative GAG release into supernatants measured. Concentrations of TNF alpha, 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. TNF alpha 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 TNF alpha was observed in explants from different sites. TNF alpha and p75 sTNF-R, but not p55 sTNF-R, concentrations were significantly higher in OA, as compared with NA, supernatants. A significant correlation between TNF alpha and p75 sTNF-R measurements was apparent only in NA supernatants. Conclusions: Variations in chondrocyte TNF-R expression occur in OA cartilage in vivo. TNF alpha 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 TNF alpha. Thus conditions exist in some OA knees for TNF alpha to contribute to focal loss of cartilage. (C) 2000 OsteoArthritis Research Society international.
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