|Budget Amount *help
¥3,100,000 (Direct Cost : ¥3,100,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1997 : ¥2,000,000 (Direct Cost : ¥2,000,000)
The prominent side effect of Cyclosporin A (CsA) and nifedipine is the induction of fibrous gingival overgrowth. The purpose of this study was to investigate the these drugs on type 1 collagen metabolism in the gingivae of 20-day-old rats feed with a powdered diet containing or lacking (control) drugs. Immunohistochemical analysis revealed that type I collagen were more prevalent in connective tissue of CsA- and nifedipine-treated gingivae than in those controls on day 55. Total RNAs from mandibular molar gingiva were isolated on days 0, 3, 8, 15, 30 and 55. Quantitative analysis of mRNA by reverse transcriptase polymerase chain reactin (RT-PCR), in CsA-treated rats, revealed a gradual decrease in expression of type I collagen and collagenase mRNAs, showing 0.4% and 18.0% on day55 compared with those on day 0, respectively. In the control groups, type I collagen and collagenase mRNAs also decreased to 19.7% and 63.0% respectively, indicating that the expression of both these products was significantly decreased in the CsA-treated group compared with controls. And in nifedipine-treated rat group, the expression of both these products was also significantly similarly decreased. Collagen phagocytosis of fibroblasts isolated from the gingiva on day 8 and 30 were measured by flow cytometry using collagen-coated latex beads. Fibroblasts isolated from CsA-treated gingiva contained 5.5% and 9.0% phagocytic cells on day 8 and 30, respectively. Whereas fibroblasts from controls contained 53.8% and 35.5% on day 8 and 30, respectively. And fibroblasts isolated from nifedipine-treated gingiva on day 30 contained 12.6% phagocytic cells. There were thus marked reductions in the proportion of phagocytic cells in connective tissue from CsA-or nifedipine-treated gingivae. Together these results indicate that drug-induced gingival overgrowth may be induced by decreased degradation of type I collagen.