Role of epigenetics in periodontal disease

• Grant number: 16/21471-0
• Support Opportunities: Scholarships abroad - Research
• Start date: November 01, 2016
• End date: October 31, 2017
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Daniela Bazan Palioto Bulle
• Grantee: Daniela Bazan Palioto Bulle
• Host Investigator: Denis F. Kinane
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Pennsylvania, United States

Abstract

In vitro: The study involves characterization of innate immune changes to P. gingivalis infection in primary human gingival epithelial cells using high throughput RNA-seq analysis and characterization of CpG methylation by methylation dependent immunoprecipitation and DNA sequencing (MeDIP) to determine the role of DNA methylation. An investigation of histone modification will be carried out to understand the mechanism and function of inflammation induced epigenetic alteration that may induce dysregulation in immune responsive genes that are critical in periodontal homeostasis. The experiment will utilize ChIP-Seq analysis to determine the histone modifications (H3K4m3, H3K27m3, H3K27ac and H3K9m3) on HiSeq 2500 Illumina platform, low throughput gene regulation antibody microarray and targeted conventional ChIP on epithelial cells to confirm ChIP-Seq data on histone modifications. Along with ChiP-seq, we will also perform conventional ChiP on specific gene locus to confirm the extent of histone modifications. In vivo: This project will use in vivo rodent model as a proof of concept to establish link between epigenetic changes and inflammatory periodontal bone loss. Oral gavage will induce "chronic" oral inflammation which we believe is suited for epigenetic study in Periodontal disease. We will also perform experiments to reverse de novo methylation changes, if any, by treating the animals with FDA approved drug, Decitabine. After the completion of infection, we will biopsy gingiva from sham- and P. gingivalis treated mice as well as the decitabine treated group and subject it to Laser Capture Micro-dissection to isolate epithelial cells for analysis using customized qPCR methylation arrays related to TLR signaling along with low through put gene expression qPCR arrays. In parallel, the maxilla will be measured for bone loss and immunohistochemistry will be performed on fixed and decalcified maxilla.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PALIOTO, DANIELA B.; FINOTI, LIVIA S.; KINANE, DENIS F.; BENAKANAKERE, MANJUNATHA. Epigenetic and inflammatory events in experimental periodontitis following systemic microbial challenge. JOURNAL OF CLINICAL PERIODONTOLOGY, v. 46, n. 8, p. 819-829, AUG 2019. (16/21471-0)