Osteoarthritic synovial fluid and synovium supernatants up-regulate tumor necrosis factor receptors on human articular chondrocytes.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Pathology and Microbiology, University of Bristol, U.K.
G R
GR
Webb
C I
CI
Westacott
C J
CJ
Elson
D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000503:physiopathology*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D013582:Synovial Fluid / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism; D015854:Up-Regulation
D000906:Antibodies; D007375:Interleukin-1; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor