2023 Volume 66 Issue 1 Pages 47-58
Purpose: Metformin (MT) has become the first-line drug for the treatment of type 2 diabetes mellitus, and studies on its effects on periodontitis have recently begun to attract attention. In this study, we aimed to clarify whether local MT administration to the gingiva is effective in preventing periodontitis.
Methods: Ten male C57BL/6J mice aged 60-70 weeks (Aged group) and ten male C57BL/6J mice aged 10 weeks (Young group) were subjected to the experiment, and were divided into two groups: an experimental group that was topically administered 1% MT solution, and a control group that was topically administered PBS. Seven days after the last administration, the mice were sacrificed and maxillary bone and peripheral venous blood samples were collected. Micro-CT images were taken of the maxillary bone, and the histological images were observed by HE staining of the tissue sections. The collected blood was analyzed for cytokines in serum. The palatal gingiva was collected from two mice in each of the Aged experimental group and the Aged control group, and the expression of wound healing-related genes from the gingiva was quantitatively analyzed. Twelve aged mice were divided into experimental and control groups as in experiment 1, and their maxillary right second molars were ligated with silk threads, and the maxillary bones were harvested after 4 days of ligation. The amount of alveolar bone resorption from micro-CT images, the number of inflammatory cells, and the number of TRAP-positive cells were measured from histological images of the maxillary bones. The Tukey test was used as a post-hoc test after analysis of variance (ANOVA) , and the significance level was set at 5%.
Results: There was no change in the amount of alveolar bone in the Aged and Young groups compared to the experimental and control groups. Histological images of the Aged experimental group showed that the junctional epithelium around the site of administration was maintained. The expression of wound-related genes was decreased in the Aged-MT group, while the expression of healing-related genes was higher in the aged-MT group. There was no significant difference in the serum cytokine levels. In Experiment 2, alveolar bone resorption in the PBS-ligated group was significantly higher than in the MT-non-ligated and PBS-non-ligated groups. The number of inflammatory cells in the MT- and MT-non-ligated groups was significantly lower than in the PBS-ligated group. The number of TRAP-positive cells was significantly higher in the PBS-ligated group than in the PBS-non-ligated, MT-ligated, and MT-non-ligated groups.
Conclusion: Local administration of MT to the gingiva of aged mice maintained the amount of collagen fibers in the gingival connective tissue and suppressed inflammation in the gingival tissue. Local administration of MT before ligation suppresses inflammation and bone resorption during the development of experimental periodontitis. These results suggest that local MT administration in the gingiva may effectively prevent the onset of periodontitis.
