Role of ascorbic acid in the regulation of epigenetic processes induced by Porphyromonas gingivalis in endothelial-committed oral stem cells

Jacopo Pizzicannella,Valentina Gatta,Guya Diletta Marconi,Francesca Diomede,Luigia Fonticoli,Thangavelu Soundara Rajan,Simone Guarnieri,Fani Konstantinidou,Oriana Trubiani,Ylenia Della Rocca

doi:10.1007/s00418-021-02014-8

Abstract

Periodontitis is a common inflammatory disease that affects the teeth-supporting tissue and causes bone and tooth loss. Moreover, in a worldwide population, periodontal disease is often associated with cardiovascular diseases. Emerging studies have reported that one of the major pathogens related to periodontitis is Porphyromonas gingivalis (P. gingivalis), which triggers the inflammatory intracellular cascade. Here, we hypothesized a possible protective effect of ascorbic acid (AA) in the restoration of the physiological molecular pathway after exposure to lipopolysaccharide derived from P. gingivalis (LPS-G). In particular, human gingiva-derived mesenchymal stem cells (hGMSCs) and endothelial-differentiated hGMSCs (e-hGMSCs) exposed to LPS-G showed upregulation of p300 and downregulation of DNA methyltransferase 1 (DNMT1), proteins associated with DNA methylation and histone acetylation. The co-treatment of AA and LPS-G showed a physiological expression of p300 and DNMT1 in hGMSCs and e-hGMSCs. Moreover, the inflammatory process triggered by LPS-G was demonstrated by evaluation of reactive oxygen species (ROS) and their intracellular localization. AA exposure re-established the physiological ROS levels. Despite the limitations of in vitro study, these findings collectively expand our knowledge regarding the molecular pathways involved in periodontal disease, and suggest the involvement of epigenetic modifications in the development of periodontitis.

Highlights

Periodontal disease is widespread, potentially affecting up to 90% of the world’s population
Results human gingiva-derived mesenchymal stem cells (hGMSCs) characterization hGMSCs were characterized following the established criteria of the International Society for Cellular Therapy to define their multipotent mesenchymal profile. hGMSCs able to differentiate into osteogenic and adipogenic lineages were maintained under proper culture conditions for 21 and 28 days, respectively
reverse transcription polymerase chain reaction (RT-PCR) data showed an increase in the mRNA expression of RUNX-2 and alkaline phosphatase (ALP) in osteogenic committed cells, and fatty acid binding protein 4 (FABP4) and peroxisome proliferator-activated receptor γ (PPARγ) in the adipogenic differentiated samples when compared to the basal cells (Fig. 1d, e)

Summary

Introduction

Periodontal disease is widespread, potentially affecting up to 90% of the world’s population. Periodontal diseases, including gingivitis and periodontitis, possess an essential bacterial multifactorial etiology, with the interaction of genetic and environmental factors (Pihlstrom et al 2005). Periodontitis is induced by microbial biofilm and caused by host-mediated inflammation, which leads to collateral tissue damage and clinical attachment loss (Hajishengallis et al 2012). The oral microbiota is composed of more than 700 different species of microorganisms (Aas et al 2005). Socransky defined the “red complex,” which includes Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as the major pathogens responsible for periodontitis progression (Socransky et al 1998). P. gingivalis can interfere with host immune responses and alter the symbiosis between the local oral bacteria,

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