Porphyromonas gingivalis Outer Membrane Vesicles Promote Gingival Fibroblasts Senescence via IL21R-AS1.

AIMS: Periodontitis, a chronic inflammatory disease, is associated with accelerated cellular senescence. This study aims to explore how Porphyromonas gingivalis (P. gingivalis) outer membrane vesicles (OMVs) induce senescence and senescence-associated secretory phenotype (SASP) in human gingival fibroblasts (HGFs), focusing on the role of lncRNAs in promoting periodontitis progression.

METHODS

In vivo, gingival senescence was assessed via immunohistochemistry while bone loss was evaluated using micro-CT, HE and TRAP staining. In vitro, HGFs senescence was validated using CCK-8, SA-β-gal staining, western blot and immunofluorescence assays. IL21R-AS1 was transfected with targeted siRNAs and overexpression plasmids to verify its function. Dual-luciferase reporter assays and rescue experiments were conducted to elucidate the competing endogenous RNA (ceRNA) mechanism of IL21R-AS1. Upstream transcription factors of IL21R-AS1 were validated by CUT&Tag-qPCR and western blot.

RESULTS

P. gingivalis OMVs induced gingival tissue senescence and alveolar bone loss in vivo. In vitro, P. gingivalis OMVs promoted HGFs senescence and SASP via IL21R-AS1. IL21R-AS1 acted as a ceRNA by sponging miR-500a-3p, thereby enhancing the regulation of FBXW7. Moreover, P. gingivalis OMVs activated TLR4 and increased PAX5 expression, leading to elevated IL21R-AS1 levels.

CONCLUSIONS

P. gingivalis OMVs promote HGFs senescence SASP by the upregulation of IL21R-AS1, which acts as a ceRNA, mediating the miR-500a-3p/FBXW7 axis and contributes to the progression of periodontitis. These findings offer novel insights into the molecular mechanisms of OMVs-induced senescence and periodontitis.