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Porphyromonas gingivalis outer membrane vesicles promote apoptosis via msRNA-regulated DNA methylation in periodontitis

ABSTRACT: The outer membrane vesicles (OMVs) produced by Porphyromonas gingivalis (P. gingivalis) contain a variety of bioactive molecules that may be involved in the progression of periodontitis. However, the participation of P. gingivalis OMVs in the development of periodontitis has not been elucidated. Here we isolated P. gingivalis OMVs and confirmed their participation in periodontitis both in vivo and in vitro. Microcomputed Tomography (micro-CT) and histological analysis showed that under the stimulation of P. gingivalis OMVs, the alveolar bone of rats was significantly resorbed in vivo. We found that P. gingivalis OMVs were taken up by hPDLCs (human Periodontal Ligament Cells, hPDLCs) in vitro, then subsequently resulting in apoptosis and inflammatory cytokines releasing which was accomplished by the microRNA-size small RNAs (msRNAs) sRNA45033 in the P. gingivalis OMVs. Through bioinformatics analysis and screening of target genes, Chromobox 5 (CBX5) was identified as the downstream target of screened-out small RNA s45033. Using dual-luciferase reporter assay, overexpression, and knockdown methods, s45033 was confirmed to target CBX5 to regulate hPDLCs apoptosis. In addition, Cleavage Under Targets and Tagmentation (Cut&Tag) analysis confirmed the mechanism that CBX5 regulates apoptosis through the methylation of p53 DNA. Collectively, these findings indicate that the role of P. gingivalis OMVs is immunologically relevant and related to bacterial virulence in the development of periodontitis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE218606 | GEO | 2022/11/30

REPOSITORIES: GEO

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