CHONDROCYTE TUMOR-NECROSIS-FACTOR RECEPTORS AND FOCAL LOSS OF CARTILAGE IN OSTEOARTHRITIS

Objective: Osteoarthritis (OA) is characterized by focal loss of carti lage. Here we show for the first time that tumor necrosis factor (TNF) alpha can act on cartilage but only at specific sites where chondrocy te TNF alpha-receptor (R) expression is high. Design: Cartilage explan ts from specified sites in the knee joints of both OA patients and non -arthritic (NA) subjects were cultured with and without TNF alpha for 14 days and cumulative glycosaminoglycan (GAG) release into the supern atant measured. p55 and p75 TNF-R expression was measured by flow cyto metry on chondrocytes isolated from the same sites. Results: Cartilage explants from different sites in knee joints from both OA patients an d NA subjects varied in their susceptibility to TNF alpha. Overall, th e proportion of samples that responded to TNF alpha was higher in cart ilage taken from OA joints than cartilage from NA subjects. Variations in p55 and p75 TNF-R expression were found between chondrocytes from different sites. p55, but not p75 TNF-R, expression on chondrocytes wa s closely related to the susceptibility of explants from the same site to TNF alpha-induced GAG loss. Conclusion: It is considered that foca l loss of cartilage will occur at sites where chondrocyte p55 TNF-R ex pression is high, if sufficient TNF alpha is present, and that these r esults identify a mechanism by which cytokine-mediated focal loss of c artilage may occur.