Extracellular Vesicles From Young Brain–Mediated Delivery of PRDX3 Ameliorates Alveolar Bone Loss in Periodontitis

AIM: To elucidate the influence and mechanism of extracellular vesicles (EVs) derived from brain tissue with ageing regulating alveolar bone resorption in periodontitis. MATERIALS AND METHODS: EVs secreted by young brain tissue (YBEVs) were assessed in a periodontitis model. Further, macrophages were treated with YBEVs or lipopolysaccharide in vitro. RNA sequencing and proteomic analysis were performed to explore how YBEVs influenced inflammatory macrophages, and the expression of peroxiredoxin 3 (PRDX3) as well as of NF-κB pathway-related factors was detected by Western blotting. PRDX3 modulators were employed to explore the NF-κB pathway's impact on inflammatory macrophage in vitro and in vivo. RESULTS: YBEVs suppressed the inflammatory response in macrophages in vitro and reduced inflammation and bone resorption in vivo. Multi-omics analyses, including cellular transcriptomics, vesicular cargo transcriptomics and single-cell profiling of brain tissue, together with in vitro and in vivo experiments, suggested that YBEVs modulated the immune response and the NF-κB signalling pathway implicating PRDX3 as a key effector. CONCLUSION: By delivering PRDX3 and inhibiting the activation of the NF-κB pathway, YBEVs inhibit inflammatory macrophages and decrease alveolar bone loss. This study provides new insight into the association between the brain and age-related periodontitis.