Tumor necrosis factor alpha can contribute to focal loss of cartilage in osteoarthritis

Citation
Ci. Westacott et al., Tumor necrosis factor alpha can contribute to focal loss of cartilage in osteoarthritis, OSTEO CART, 8(3), 2000, pp. 213-221
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Rheumatology,"da verificare
Journal title
OSTEOARTHRITIS AND CARTILAGE
ISSN journal
1063-4584 → ACNP
Volume
8
Issue
3
Year of publication
2000
Pages
213 - 221
Database
ISI
SICI code
1063-4584(200005)8:3<213:TNFACC>2.0.ZU;2-5
Abstract
Objective: To evaluate the potential for tumor necrosis factor alpha (TNF a lpha)-induced focal loss of cartilage in osteoarthritic (OA) knee joints. Design: Fresh cartilage from specified regions of OA joints was immunostain ed for TNF-receptor (R) bearing chondrocytes. Cartilage explants from the s ame regions were cultured with or without small amounts of TNF alpha and cu mulative GAG release into supernatants measured. Concentrations of TNF alph a, p55 and p75 soluble (s) TNF-R in supernatants from cultured OA and non-a rthritic (NA) synovium were measured by ELISA. Results: TNF-R bearing chondrocytes were identified in OA cartilage; more s pecimens contained p55 TNF-R- than p75 TNF-R-bearing chondrocytes and diffe rences in TNF-R distribution were apparent in cartilage from different regi ons of the same knees. TNF alpha at 5, 1, 0.5 and 0.25 ng/ml (but not 0.1 n g/ml) significantly increased glycosaminoglycans (GAG) release from cartila ge 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 cartila ge in vivo. TNF alpha at concentrations produced by OA synovium in vitro, c an degrade cartilage matrix. In most OA supernatants sTNF-R concentrations were insufficient to abrogate the effects of TNF alpha. Thus conditions exi st in some OA knees for TNF alpha to contribute to focal loss of cartilage. (C) 2000 OsteoArthritis Research Society international.