To determine whether the up-regulation of chondrocyte tumor necrosis factor receptor (TNF-R) expression in osteoarthritis (OA) is due to molecules released within the OA knee joint.
Non-arthritic (NA) human articular chondrocytes were incubated with normal serum, OA synovial fluid, or supernatants from either cultured NA or OA synovium, and TNF-R expression measured by flow cytometry.
OA synovial fluid, but not normal serum, significantly up-regulated the proportion of chondrocytes expressing p55 TNF-R as well as the number of p55 TNF-R/chondrocyte. Similarly, supernatants from OA, but not NA, synovia significantly up-regulated chondrocyte p55 TNF-R expression. Chondrocyte p75 TNF-R expression was also significantly increased by some of the OA supernatants but not others, and overall no significant increase was seen. OA synovium supernatants contained higher concentrations of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) than NA synovium supernatants and neutralizing antibodies to these cytokines either partially or totally abrogated the ability of the OA supernatants to increase chondrocyte p55 TNF-R expression. Finally, various concentrations of recombinant human (rh)IL-1 beta and rhIL-6 up-regulated chondrocyte p55 TNF-R expression.
These results suggest that IL-1 and IL-6 produced by OA synovium contribute to the progression of the disease by rendering chondrocytes more susceptible to stimulation by catabolic cytokines.