Synergism between muramyl dipeptide and lipopolysaccharide in the inhibition of glycosaminoglycan synthesis in cultured rat costal chondrocytes

The effect of synthetic muramyl dipeptide on glycosaminoglycan synthesis in cultured rat costal chondrocytes was examined. Muramyl dipeptide alone had no effect on the glycosaminoglycan synthesis of rat chondrocytes, whereas Escherichia coli lipopolysaccharide and interleukin 1α inhibited glycosaminoglycan synthesis in a dose dependent manner. Muramyl dipeptide, when added to chondrocyte cultures in the presence of lipopolysaccharide, enhanced the lipopolysaccharide induced inhibition of glycosaminoglycan synthesis in a dose dependent manner. Adjuvant active analogues of muramyl dipeptide, but not adjuvant inactive analogues, also enhanced the lipopolysaccharide induced inhibition of glycosaminoglycan synthesis. In combination with muramyl dipeptide, to inhibit glycosaminoglycan synthesis, lipopolysaccharide could be replaced with the synthetic lipid A, an active principle of lipopolysaccharide. These results show that the muramyl dipeptide portion of bacterial peptidoglycan enhances the susceptibility of rat chondrocytes to the lipid A portion of bacterial lipopolysaccharide, and therefore the interaction between chondrocytes and bacterial cell wall components might be involved in damaging the cartilage in inflammatory joint diseases.