Inhibition of Dynamin-Related Protein 1-Dependent Mitochondrial Fission Ameliorates Apical Periodontitis by Attenuating NLRP3 Inflammasome-Mediated M1 Macrophage Polarisation

作者：Yao Yang, Min Li, Lifei Pan, Yifei Tang, Yuting Wang, Xiaoyue Guan, Tiezhou Hou, Siyu Hou · 发表于：International Dental Journal · 年份：2025 · DOI：10.1016/j.identj.2025.100853 · 被引用次数：11 · 研究领域：Oral microbiology and periodontitis research、Endodontics and Root Canal Treatments、Inflammasome and immune disorders

INTRODUCTION AND AIMS: The aim of this study was to determine if Dynamin-related protein 1 (Drp1) -dependent mitochondrial fission is involved in the pathological process of apical periodontitis and elucidate the underlying mechanisms. METHODS: Immunohistochemistry, immunofluorescence, and western blotting assessed CD86 expression, NLRP3/Caspase1/IL-1β activation, and mitochondrial dynamics-related proteins in human periapical macrophages. In vitro apical periodontitis (AP) models used macrophages stimulated with P. gingivalis LPS (Pg-LPS), pretreated with/without Drp1 inhibitor Mdivi-1 or NLRP3 inhibitor MCC950. CD86, NLRP3/Caspase1/IL-1β, mitochondrial dynamics proteins, TNF, and IL-6 were quantified via western blot, RT-qPCR, or immunofluorescence. ROS (DCFH-DA), ATP (commercial kit), mitochondrial membrane potential (JC-1), and morphology (TEM, MitoTracker/immunofluorescence) were analysed. Multimodal approaches explored Drp1-mediated mitochondrial fission and NLRP3 inflammasome-dependent M1 polarisation. Mdivi-1-treated AP models were established to dissect Drp1's role in pathogenesis. RESULTS: , rescued mitochondrial dysfunction, and further suppressed the activation of NLRP3/Caspase1/IL1β and the expression of CD86. In vivo experiments showed that Mdivi-1 treatment could significantly alleviate the inflammatory bone erosion at the apex in a murine AP model by inhibiting macrophage polarisation and the NLRP3 inflammatory pathway. CONCLUSION: Drp1-mediated excessive mito...