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

Abstract

Objective To evaluate the potential for tumor necrosis factor alpha (TNFα)-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 TNFα and cumulative GAG release into supernatants measured. Concentrations of TNFα, 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. TNFα at 5, 1, 0.5 and 0.25ng/ml (but not 0.1ng/ml) significantly increased glycosaminoglycans (GAG) release from cartilage explants in a dose-dependent manner. Variation in susceptibility to TNFα was observed in explants from different sites. TNFα and p75 sTNF-R, but not p55 sTNF-R, concentrations were significantly higher in OA, as compared with NA, supernatants. A significant correlation between TNFα and p75 sTNF-R measurements was apparent only in NA supernatants.Conclusions Variations in chondrocyte TNF-R expression occur in OA cartilage in vivo. TNFα 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 TNFα. Thus conditions exist in some OA knees for TNFα to contribute to focal loss of cartilage.