A Vicious Circle Between Periodontitis And Clonal Hematopoiesis

Elucidating the molecular mechanisms underlying the bidirectional regulation between DNMT3A mutation-driven clonal hematopoiesis and periodontitis. This project will utilize a Dnmt3a R878H mouse model with hematopoietic system-specific mutations. Through competitive bone marrow transplantation experiments and silk ligature-induced periodontitis modeling by ligating the maxillary second molars in mice, we aim to clarify the interaction between Dnmt3a mutation-driven clonal hematopoiesis and periodontitis by examining periodontitis-related parameters, blood cells, and bone marrow cells. Methylation sequencing, RNA-Seq, and cytokine array analyses will be employed to investigate the bidirectional regulatory mechanisms between Dnmt3a mutation-driven clonal hematopoiesis and periodontitis. Furthermore, gene editing and small molecule drugs will be used to validate the critical roles of key molecules. These findings will serve as therapeutic targets for intervention, providing novel insights for the diagnosis and treatment of periodontal diseases. 1. In the periodontitis model of R878H mutant mice, there is an abnormal increase in gingival inflammatory cells and aggravated bone resorption; 2.Periodontitis promotes the increase of peripheral blood myeloid cells in the Dnmt3a mutation-driven clonal hematopoiesis model, and also increases hematopoietic stem cells in the bone marrow. Clonal hematopoiesis driven by DNMT3A R878H fuels a vicious cycle of inflammation in periodontitis.