Porphyromonas gingivalis lipopolysaccharide stimulation in human periodontal ligament stem cells: role of epigenetic modifications to the inflammation

Abstract

Periodontitis is a chronic oral inflammatory disease produced by bacteria. Gingival retraction and bone and connective tissues resorption are the hallmarks of this disease. Chronic periodontitis may contribute to the risk of onset or progression of neuroinflammatory pathological conditions, such as Alzheimer’s disease. The main goal of the present study was to investigate if the role of epigenetic modulations is involved in periodontitis using human periodontal ligament stem cells (hPDLSCs) as an in vitro model system. hPDLSCs were treated with lipopolysaccharide of Porphyromonas gingivalis and the expression of proteins associated with DNA methylation and histone acetylation, such as DNMT1 and p300, respectively, and inflammatory transcription factor NF-kB, were examined. Immunofluorescence, Western blot and next generation sequencing results demonstrated that P. gingivalis lipopolysaccharide significantly reduced DNA methylase DNMT1, while it markedly upregulated the level of histone acetyltransferase p300 and NF-kB in hPDLSCs. Our results showed that P. gingivalis lipopolysaccharide markedly regulate the genes involved in epigenetic mechanism, which may result in inflammation induction. We propose that P. gingivalis lipopolysaccharide-treated hPDLSCs could be a potential in vitro model system to study epigenetics modulations associated with periodontitis, which might be helpful to identify novel biomarkers linked to this oral inflammatory disease.

Possible role of Porphyromonas gingivalis in orodigestive cancers

“…Epigenetic modification includes chemical changes in DNA and associated proteins. This can lead to remodeling of the chromatin and activation/inactivation of gene transcription [85]. Such changes can contribute to cancer and autoimmune and inflammatory diseases including periodontitis.…”

“…Indeed, aberrant DNA methylation has been found in gingival tissue [87,88]. Recently, it was shown that P. gingivalis LPS markedly regulates genes involved in epigenetic mechanisms [85].…”

Is there a link between genetic defects in the complement cascade andPorphyromonas gingivalisin Alzheimer’s disease?

“…Epigenetic modifications lead to chemical changes in DNA and associated proteins which cause remodeling of the chromatin and activation or inactivation of gene transcription. These changes can contribute to development and maintenance of cancer, autoimmune and inflammatory diseases, including periodontitis [103,104].…”

Effect of scaling and root planing on level of immunoglobulin E and immunoglobulin G4in children with gingivitis and house-dust mite allergy: A pilot randomised controlled trial

“…45 Previous studies demonstrated the pathogenic role of Pg dental biofilm to stimulate LPS-driven inflammatory responses, 46 and therefore, lack of dental plaque and calculus in supra-gingival surface, sub-gingival surface and human epithelial cell rests of Malassez accounted for the lack of response to LPS to induce sensitisation of atopic inflammatory responses. 47,48 Moreover, given the unique LPS-induced atopic inflammatory responses, we can control atopic inflammatory responses by removing dental biofilm. This reduces the subject body's load of LPS-triggered mast cells derived from periodontal inflammation.…”