Bionanoparticle - Tageted Inhibition Of Drp1 Reduces Bone Resorption In Periodontitis

To clarify whether Drp1 mediates mitochondrial homeostatic imbalance involved in regulating osteoclast differentiation and its specific mechanism in the periodontal inflammatory microenvironment. And to design effective strategies to target depletion of osteoclasts in the periodontitis microenvironment. Using immunofluorescence co-localization analysis, siRNA combined with Ad-Dnm1l to regulate Dnm1l and analyze the effect of Drp1 on the differentiation of pOCs. And combined with untargeted metabolomics to detect differential metabolites and enrich metabolic pathways to explore the effect of Drp1 on pOCs metabolism. Synthesize spatiotemporally selective biomimetic nanoparticles of pOCs and probe the homologous targeting ability; analyze their mitochondrial protective effects by Trap staining and qPCR. Construct an experimental periodontitis model and evaluate the periodontal bone resorption; detect the depletion of osteoclasts in the periodontal tissues by immunological staining. Mitochondrial dynamics imbalance occurs in pOCs under the inflammatory microenvironment, with increased expression of Drp1, which increases their mitochondrial division, triggers mitochondrial metabolic reprogramming, causes aggregation of the metabolite succinic acid, and activates the downstream inflammatory signaling pathway, promoting the differentiation of pOCs to mOCs. Biomimetic nanoparticles with spatio-temporal selectivity of pOCs alleviate periodontitis bone resorption by targeting recognition of pOCs, exerting mitochondrial protection of pOCs, and depleting osteoclasts. The present study elucidates the abnormal mitochondrial morphology and functional manifestation and its specific mechanism in pOCs cells under inflammatory microenvironment and targeted depletion of osteoclasts, which may provide a new strategy for precision treatment of periodontitis.