D-mannose alleviated alveolar bone loss in mice with experimental periodontitis via regulating the anti-inflammatory effect of amino acids.

BACKGROUND: Periodontitis is a chronic infectious disease caused by dysbiosis of oral microbiota, ultimately leading to periodontal alveolar bone loss. The oral subgingival microbiome, a key role in periodontitis pathogenesis, could alter the composition of gut microbiomes resulting in intestinal microbiota disorder. D-mannose plays an important role in glucose metabolism; whether it is beneficial to prevention and treatment of periodontitis and the regulation of oral and intestinal microbiota changes is still unknown. METHODS: To explore the effect of D-mannose, we established experimental periodontitis models in mice and then treated with supplementation of D-mannose in drinking water or gavage to examine the extent of periodontal bone loss using methylene blue staining. Moreover, the oral and fecal samples of mice were collected for 16S rRNA deep sequencing to analyze the changes of oral and gut microbiota after 14 days. Furthermore, amino acid content assays were used to test the concentration of amino acid of gingival tissues and intestinal tissues. RESULTS: We found that D-mannose could alleviate periodontal bone loss whether in the manner of drinking water or gavage. 16S rRNA results revealed that the abundance of Firmicutes changed significantly in oral samples, while Firmicutes and Akkermansia muciniphila were dominated in gut microbiota. In addition, we demonstrated that D-mannose inhibited inflammation and alleviated alveolar bone loss in periodontitis via regulating amino acid metabolism of oral and gut microbiomes. CONCLUSION: Our findings provided insight into the mechanism underlying the abilities of D-mannose in improving periodontitis treatment, suggesting that D-mannose has potential application in the dental clinic.

miR-4651 inhibits cell proliferation of gingival mesenchymal stem cells by inhibiting HMGA2 under nifedipine treatment.

Drug-induced gingival overgrowth (DIGO) is recognized as a side effect of nifedipine (NIF); however, the underlying molecular mechanisms remain unknown. In this study, we found that overexpressed miR-4651 inhibits cell proliferation and induces G0/G1-phase arrest in gingival mesenchymal stem cells (GMSCs) with or without NIF treatment. Furthermore, sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis, bioinformatics analysis, and dual-luciferase report assay results confirmed that high-mobility group AT-hook 2 (HMGA2) is the downstream target gene of miR-4651. Overexpression of HMGA2 enhanced GMSC proliferation and accelerated the cell cycle with or without NIF treatment. The present study demonstrates that miR-4651 inhibits the proliferation of GMSCs and arrests the cell cycle at the G0/G1 phase by upregulating cyclin D and CDK2 while downregulating cyclin E through inhibition of HMGA2 under NIF stimulation. These findings reveal a novel mechanism regulating DIGO progression and suggest the potential of miR-4651 and HMGA2 as therapeutic targets.