Porphyromonas gingivalis OMVs promoting endothelial dysfunction via the STING pathway in periodontitis

Abstract Objective This study aimed to assess the effects of Porphyromonas gingivalis outer membrane vesicles ( Pg ‐OMVs) in chronic periodontitis and explore the underlying mechanism involved. Methods In vitro, Pg‐OMVs were incubated with Ea.hy926 (vessel endothelial cells, ECs) to evaluate their effects on endothelial functions and to investigate the underlying mechanism. The effects of endothelial dysfunction on MG63 osteoblast‐like cells were verified using an indirect co‐culture method. For in vivo studies, micro‐CT was conducted to identify alveolar bone mass. Immunofluorescence staining was conducted to confirm the levels of stimulator of interferon genes (STING) in the blood vessel and the number of Runx2 + cells around the alveolar bone. Results Pg ‐OMVs were endocytosed by ECs, leading to endothelial dysfunction. The cGAS‐STING‐TBK1 pathway was activated in ECs, which subsequently inhibited MG63 migration and early osteogenesis differentiation. In vivo, Pg ‐OMVs promoted alveolar bone resorption, increased STING levels in the blood vessel, and decreased Runx2 + cells around the alveolar bone. Conclusions Pg ‐OMVs caused endothelial dysfunction and activated the cGAS‐STING‐TBK1 signal cascade in ECs, thereby impairing ECs‐mediated osteogenesis. Furthermore, Pg ‐OMVs aggregated alveolar bone loss and altered the blood vessel‐mediated osteogenesis with elevated STING.