Effects of recombinant human osteogenic protein 1 on the production of proteoglycan, prostaglandin E2, and interleukin-1 receptor antagonist by human articular chondrocytes cultured in the presence of interleukin-1β

Objective. Recombinant human osteogenic protein 1 (OP-1) is an effective stimulator of human cartilage S-35-proteoglycan synthesis. The present study was conducted to determine whether stimulation of human articular chondrocytes with OP-1 can help overcome interleukin-1 beta (IL-1 beta)-induced suppression of S-35-proteoglycan synthesis. Methods. Human articular chondrocytes in alginate beads were maintained for 3 days in the absence (control) or presence of IL-1 beta at 0.1-100 pg/ml with or without OP-l at 50 ng/ml, in medium containing 10% fetal bovine serum (FBS). Incorporation of S-35-sulfate into proteoglycans was quantified during the last 4 hours of culture and reported as counts per minute per mu g DNA, Release of interleukin-l receptor antagonist (IL-1Ra) and prostaglandin E-2 into the medium was monitored by immunoassay. Results. IL-1 beta at 10 pg/ml caused a 60% decrease in S-35-proteoglycan synthesis, This could be blocked by including 500 ng/ml IL-1Ra in the medium. The presence of 50 ng/ml OP-1 in the IL-1 beta-containing medium was effective in restoring S-35-proteoglycan synthesis to the level of that found in cultures not treated with IL-1 beta. The restorative effects of OP-1 and IL-1Ra were cumulative. The rate of release of prostaglandin E-2 and IL-1Ra into the medium was not affected by the presence of OP-1. Conclusion, Treatment of human articular chondrocytes with OP-1 cultured in the presence of FBS is effective in overcoming the down-regulation of proteoglycan synthesis induced by low doses of IL-1 beta.