Diabetes induces disorders in macrophage immunometabolism, leading to increased destruction of periodontal tissue. Identifying key factors to restore metabolic alterations and promote resolution of inflammation remains an unmet objective. In the present study, the effect of macrophage efferocytosis on inflammatory regression and tissue repair was assessed using a diabetic periodontitis (DPD) model. The mitochondrial function of macrophages cultured under different conditions was assessed in vitro, and macrophage efferocytosis function and polarization phenotypes were examined. Osteogenic differentiation and migration capacity were examined using periodontal ligament stem cells (PDLSCs) co-cultured with macrophages to assess the effect on tissue repair. We demonstrated that the high-glucose inflammatory microenvironment exacerbated the pro-inflammatory metabolic profile of macrophages and disrupted mitochondrial dynamics. Rats with DPD exhibited heightened periodontal tissue damage during the ligation period, characterized by increased neutrophil infiltration and apoptotic cells. Following ligature removal, the transition to the repair phase was inhibited. Impaired efferocytosis in macrophages led to reduced expression of anti-inflammatory cytokines. Inhibiting excessive mitochondrial division mitigated macrophage damage, ultimately improving the osteogenic differentiation and migration of PDLSCs. This research suggested the critical role of mitochondria in the resolution of inflammation in diabetic periodontitis through regulating macrophage efferocytosis and interaction with PDLSCs.
Liu et al. (Mon,) studied this question.