Outer membrane vesicles of Porphyromonas gingivalis impede bone regeneration by inducing ferroptosis via the Hippo-YAP signaling pathway

作者：Xinghong Luo, Yanzhen Wang, Tingting Ning, Qian Lei, Hao Cui, Xianghui Zou, Yan Chen, Shuoling Chen, Xinyao Zhang, Shenglong Tan, Dandan Ma · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03457-0 · 被引用次数：16 · 研究领域：Ferroptosis and cancer prognosis、Oral microbiology and periodontitis research、Cancer-related molecular mechanisms research

BACKGROUND: Although increasing evidence confirms that oral microbiota imbalance is a critical factor inhibiting bone regeneration, the specific mechanisms have remained unexplored. This study aims to use periodontitis as a model of oral microbiota imbalance to investigate the specific mechanisms that inhibit bone regeneration in extraction sockets. METHODS: Cone Beam Computed Tomography (CBCT) data of extraction sockets were collected from patients with and without periodontitis to confirm the influence of the periodontitis microenvironment on bone regeneration in extraction sockets. Furthermore, GW4869-pretreated Porphyromonas gingivalis (Pg) and normal Pg were used to build a periodontitis model, and then the bone regeneration in extraction sockets under these conditions was detected by H&E staining, Masson's staining and micro-CT analysis. In vitro, the effect of Pg-derived OMVs on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was examined. RNA sequencing, FerroOrange, malondialdehyde assay, transmission electron microscopy, qRT‒PCR, and western blotting analysis were performed. RESULTS: CBCT analysis showed that periodontitis significantly inhibited new bone formation in the extraction sockets in patients. Micro-CT and Histological analysis revealed that inhibiting OMVs released from Pg alleviated the inhibition of bone regeneration in extraction sockets under Pg imbalance. Moreover, Pg-derived OMVs treatment deteriorated bone regeneration in e...