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.