Oral diseases · 2024
Porphyromonas gingivalis OMVs promoting endothelial dysfunction via the STING pathway in periodontitis.
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Chen Zhenwei, Cao Ye, Jiang Wenxiu, Yan Zixin, Cai Guanhui, Ye Junjie, Wang Hua, Liu Luwei
Аннотация
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.
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.
Предметные рубрики MeSH
Porphyromonas gingivalisHumansMembrane ProteinsEndothelial CellsSignal TransductionAnimalsOsteogenesisAlveolar Bone LossProtein Serine-Threonine KinasesChronic PeriodontitisMaleMiceExtracellular VesiclesCell MovementCoculture TechniquesCore Binding Factor Alpha 1 SubunitCell DifferentiationOsteoblastsFemaleNucleotidyltransferasesSTING ProteinCyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase