THE RECOVERY OF ARTICULAR-CARTILAGE IN EXPLANT CULTURE FROM INTERLEUKIN-1-ALPHA - EFFECTS ON PROTEOGLYCAN SYNTHESIS AND DEGRADATION

The cytokine interleukin-1 (IL-1) strongly inhibits proteoglycan biosy nthesis and increases extracellular proteoglycan degradation in cartil age. In this study we investigated how quickly proteoglycan turnover r ecovered after IL-1 treatment. Porcine articular cartilage in explant culture was incubated with recombinant human (rh) IL-1 alpha, rh insul in-like growth factor (IGF)-1 or rh-transforming growth factor (TGF)-b eta 1 for 3 days. RhIL-1 alpha strongly inhibited synthesis and promot ed matrix degradation over 3 days, whereas rhIGF-1 stimulated proteogl ycan synthesis, and rhTGF-beta 1 had no significant effect on synthesi s. In the absence of serum, the recovery of proteoglycan synthesis aft er IL-1 treatment (10 ng/ml) for 3 days was extremely slow, and it rem ained 30% inhibited even after a further 8 days of recovery. Matrix de gradation of proteoglycan assessed from the rate of release of glycosa minoglycan into the culture medium recovered more quickly and was grea tly reduced within 3 days. Shorter exposure of explants to IL-1 alpha (8 h) resulted in less inhibition of synthesis, but it did not result in a more rapid rate of recovery following its removal. Treatment of c artilage with IGF-1 (20 ng/ml) or TGF-beta(10 ng/ml) during the recove ry period increased the rate of recovery of both synthesis and degrada tion. Synthesis recovered to control rates within 6 days and degradati on within 2 days. TGF-beta (10 ng/ml) was slightly more potent than IG F-1. Fetal calf serum (10% v/v) also promoted recovery in a similar wa y to the growth factors. The effect of IGF-1 in stimulating proteoglyc an synthesis in IL-1-treated cartilage was similar to its effect on co ntrol untreated cartilage, but whereas TGF-beta also stimulated proteo glycan synthesis in IL-1-treated cartilage, it did not stimulate synth esis at even up to 100 ng/ml in control tissue. The results show that the reactivation of aggrecan gene expression following IL-1 treatment is very slow even in the presence of the growth factors IGP-1 and TGF- beta, whereas the rate of matrix degradation returns to control level more quickly.