Inhibition of cartilage breakdown by hydrocortisone in a tissue culture model of rheumatoid arthritis

Abstract

Bovine nasal cartilage discs cocultured with human rheumatoid synovial membrane or synovial-membrane-conditioned media release proteoglycan largely as a result of cartilage breakdown. We assessed the effects of hydrocortisone on proteoglycan distribution between cartilage and culture medium, and on cartilage breakdown expressed as the release of either proteoglycan or 35S-products from prelabelled discs. The presence of synovial membrane inhibited the capacity for net proteoglycan synthesis, preventing its accumulation in cartilage; this was little affected by hydrocortisone. The major response to pharmacological concentrations of hydrocortisone was suppression of both spontaneous and synovial-membrane-induced cartilage breakdown. The autolysis of synovial protein that normally occurred during culture was similarly prevented by comparable doses of corticosteroid. Changes in chromatographic distribution of the 35S-labelled degradation products released from cartilage conformed with a corticosteroid-induced inhibition of endogenous lysosomal or related proteinase activity. Additionally, inhibition of the early events in synovial membrane that are responsible for chondrocyte-mediated breakdown of cartilage may contribute significantly to the overall corticosteroid effect.