INTERLEUKIN-1 REVERSIBLY INHIBITS THE SYNTHESIS OF BIGLYCAN AND DECORIN IN INTACT ARTICULAR-CARTILAGE IN CULTURE

Objective. To study the effect of interleukin-1 (IL-1) on the synthesi s of proteoglycans biglycan (DSPG-I) and decorin (DSPG-II) in intact b ovine articular cartilage. Methods. Cartilage bearing sesamoid bones f rom the metacarpophalangeal joint were cultured with 10 ng/ml IL-1 for 2 days and labelled with [S-35] sulfate. One sesamoid bone from each animal had been labelled ex vivo. The remaining 2 were cultured with I L-1 and allowed to recover in control medium before labelling. Control cultures were maintained in medium without IL-1 and labelled concurre ntly with the experimental series. The dermatan sulfate proteoglycans were purified from 4 M guanidinium chloride extracts of the cartilage by gel filtration on Sepharose CL-2B and CL-4B, on which they appeared as a single peak. Biglycan and decorin were separated by sodium dodec yl sulfide polyacrylamide gel electrophoresis in high salt. Individual lanes from the gel were cut in slices, which were dissolved and count ed for radioactivity. Results. Ex vivo, biglycan accounted for 4% and decorin for 2% of total incorporated sulfate. IL-1 reduced the synthes is of biglycan to 77% of the level of cultured controls and that of de corin to 73%. The synthesis of both proteoglycans returned to the cont rol levels when the IL-1 was removed. IL-1 (10 ng/ml, 2 days) had no s ignificant effect on total proteoglycan synthesis. Conclusion. The inh ibition of synthesis of biglycan and decorin by IL-1 might be importan t in the pathophysiology of cartilage destruction in rheumatic disease s.