heparitin-sulfate and Gingival-Overgrowth

Glycosaminoglycans are thought to accumulate in formative lesions like drug-induced gingival overgrowth. Recent evidences, however, suggest that the amounts of glycosaminoglycans are comparable in overgrown and healthy gingiva. Besides, alterations in the size distribution of glycosaminoglycan molecules isolated from phenytoin-induced overgrown samples have also been suggested. Therefore, we sought to determine possible differences in molecular size distribution of gingival glycosaminoglycans in other types of drug-induced overgrowths. Purified gingival glycosaminoglycans from healthy and cyclosporin- and nifedipine-induced overgrown gingival tissues were analyzed by agarose gel electrophoresis and their molecular-size distribution was evaluated by both gel filtration chromatography and polyacrylamide gel electrophoresis. Our results on the gingival glycosaminoglycan composition showed presence of chondroitin sulfate, dermatan sulfate, heparan sulfate and hyaluronic acid in all types of gingival tissues examined. In addition, hyaluronic acid was predominantly of a large size eluting near to the void volume of a Superose-6 column, while the sulfated glycosaminoglycans were mainly composed of low molecular size glycosaminoglycans. Our results show no differences in the molecular-size distribution of hyaluronic acid and sulfated glycosaminoglycans among healthy and drug-induced overgrown gingival tissues.

Topics: Adolescent; Adult; Calcium Channel Blockers; Chondroitin Sulfates; Chromatography, Gel; Cyclosporine; Dermatan Sulfate; Electrophoresis, Agar Gel; Electrophoresis, Polyacrylamide Gel; Gingiva; Gingival Overgrowth; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Immunosuppressive Agents; Middle Aged; Molecular Structure; Molecular Weight; Nifedipine; Sepharose

Glycosaminoglycans in normal and cyclosporin-induced gingival overgrowth were extracted by papain digestion and purified by Mono Q-FPLC chromatography. The purified glycosaminoglycans were analyzed by agarose gel electrophoresis and by the pattern of degradation products formed by chondroitin lyases on HPLC chromatography. Our results on the glycosaminoglycan composition showed presence of chondroitin 4- and 6-sulfate, dermatan sulfate, heparan sulfate and hyaluronic acid in both normal gingiva and cyclosporin-induced gingival overgrowth. The total and relative amounts of glycosaminoglycans were similar between normal and overgrown gingiva. This suggests that the glycosaminoglycan composition is not changed in cyclosporin-induced gingival overgrowth. Our present biochemical results conflict with histochemical and biosynthetic data previously reported by other groups. Those studies suggested that the affected tissues contained higher levels of glycosaminoglycans and that cyclosporin induced comparably high levels of these compounds in in vitro cultures of gingival fibroblasts. Therefore, these discrepant results suggest that a cyclosporin-induced increase on gingival glycosaminoglycans still remains an open question. The implications of these conflicting results are discussed.

Topics: Adult; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Cyclosporine; Dermatan Sulfate; Electrophoresis, Agar Gel; Extracellular Matrix Proteins; Gingival Overgrowth; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Immunosuppressive Agents; Middle Aged