heparitin-sulfate and Gingival-Hyperplasia

The overgrowth-affected gingiva of patients treated with cyclosporin A after kidney transplant was examined with ultrastructural and histochemical methods to evaluate the involvement of connective tissue. Gingival overgrowth has the same clinical signs as local edema. The ultrastructural study showed that the dimensional increase was largely due to increased production of amorphous ground substance by fibroblasts, possibly resulting from an increased release of histamine by mast cells. The histochemical data revealed that the affected tissues contained higher levels of glycosaminoglycans and that cyclosporin A induced comparably high levels of glycosaminoglycans in in vitro cultures of fibroblasts obtained from normal gingiva. The combination of ultrastructural and histochemical data, therefore, strongly suggests that the response of the connective tissue in gingival overgrowth cannot be ignored and may be the main cause of the observed pathological condition.

Topics: Alcian Blue; Capillaries; Chondroitin Sulfates; Coloring Agents; Connective Tissue; Cyclosporine; Dermatan Sulfate; Edema; Epithelium; Fibroblasts; Gingiva; Gingival Hyperplasia; Glycosaminoglycans; Heparin; Heparitin Sulfate; Histamine Release; Humans; Immunosuppressive Agents; Keratan Sulfate; Kidney Transplantation; Mast Cells; Tetrapyrroles

Although drug-induced gingival hyperplasia has been extensively studied, the pathogenesis of this disorder has not been clarified to date. Transforming growth factor beta (TGF beta) and basic fibroblast growth factor (bFGF) have been shown to be implicated in diverse fibrotic and hyperplastic diseases. Heparan sulphate proteoglycan (HSPG), which is composed of heparan sulphate glycosaminoglycan (HSGAG), has also been shown to play an important role in the pathogenesis of tissue overgrowth by enhancing the functions of bFGF. However, the possible implication of these growth factors in gingival hyperplasia has not been studied. Immunohistochemical localization of TGF beta, bFGF, their receptors and HSGAG was studied in 4 nifedipine-induced and 5 phenytoin-induced hyperplastic gingival tissues, and 5 non-hyperplastic control gingival tissues to elucidate the pathogenesis of this disease. Significant immunostaining against TGF beta, bFGF, the receptors of these two growth factors and HSGAG was observed in the lamina propria of hyperplastic gingival tissues while less immunostaining was observed in the controls. The mean numbers of immunostained cells against TGF beta, bFGF, their receptors in a square unit (0.1 x 0.1 mm) of the lamina propria, which were counted to 10 units of each hyperplastic gingival tissue, were significantly higher than those of the controls. The results suggest that the increased synthesis of TGF beta, bFGF, their receptors and HSGAG may be related to the pathogenesis of drug-induced gingival hyperplasia.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Calcium Channel Blockers; Cell Count; Coloring Agents; Female; Fibroblast Growth Factor 2; Gingiva; Gingival Hyperplasia; Heparitin Sulfate; Humans; Immunohistochemistry; Male; Nifedipine; Phenytoin; Receptors, Fibroblast Growth Factor; Receptors, Growth Factor; Receptors, Transforming Growth Factor beta; Transforming Growth Factor beta