P. gingivalis OMVs Attenuate the Osteogenesis of PDLSCs by Activating PERK Signaling.

Abstract

OBJECTIVE: The Porphyromonas gingivalis outer membrane vesicles (P. gingivalis OMVs) carry toxins that contribute to the onset and progression of periodontitis. These OMVs have been implicated in host cell invasion and damage. This study aimed to determine the role and potential mechanisms of P. gingivalis OMVs on periodontal inflammation. METHODS: A model of PDLSCs induced by P. gingivalis OMVs was developed, and changes in their biological functions were examined. We established a rat periodontitis model to confirm whether P. gingivalis OMV promotes the periodontal inflammatory phenotype. Additionally, the potential mechanisms by which P. gingivalis OMVs impair the osteogenic differentiation capacity of PDLSCs were investigated. RESULTS: P. gingivalis OMVs inhibited the proliferation, promoted apoptosis and suppressed the osteogenesis of PDLSCs, while promoting periodontal inflammatory phenotype in vivo. Furthermore, mechanistic studies revealed that pretreatment of PDLSCs with 4-phenylbutyric acid (4-PBA) prevented the P. gingivalis OMVs-induced activation of the PERK pathway and restored the osteogenesis of PDLSCs. CONCLUSIONS: We demonstrate that P. gingivalis OMV exacerbates the periodontitis phenotype and inhibits the regenerative function of PDLSCs, potentially through mechanisms involving endoplasmic reticulum dysfunction.