Comparative Effects of Cyclosporin on Glycosaminoglycan Synthesis by Gingival Fibroblasts

Histological studies show that drug-induced gingival overgrowth results from an accumulation of the connective tissue component. Despite comprising a major part of gingival connective tissue, a role for glycosaminoglycans (GAGs) in the pathogenesis of gingival overgrowth has received scant attention. By analyzing the metabolism of 3H-glucosamine, we have compared GAG and hyaluronan synthesis by fibroblasts derived from normal and overgrown gingival tissue, and the effects of cyclosporin on GAG output. GAG production was cell density-dependent, fibroblasts cultured at low density synthesizing significantly increased quantities in comparison to confluent cultures. The effects of cyclosporin on GAG synthesis was also found to be both cell density- and cell strain-dependent. However, cyclosporin-stimulated GAG synthesis by 2/3 overgrown cell strains and 1/3 normal strains. These results suggest that a direct promotion of GAG synthesis by gingival fibroblasts in response to cyclosporin may play a role in the pathogenesis of gingival overgrowth.