DOI
https://doi.org/10.25772/NDSA-JH75
Author ORCID Identifier
https://orcid.org/0000-0001-7705-3467
Defense Date
2023
Document Type
Thesis
Degree Name
Master of Science in Dentistry
Department
Dentistry
First Advisor
Zhao Lin
Abstract
Background: Emerging data has indicated the significant role of epigenetic control in inflammation. Acetylation of lysine residues on histones is a major epigenetic modification of chromatin, which is required for cytokine gene expression and regulated in inflammatory diseases. It has been shown that periodontal bacteria induce histone acetylation in oral epithelial cells and experimental periodontitis in rodents. In this study, we investigated the acetylation level of histone 3 (H3) in gingival tissue from healthy and periodontitis patients. We hypothesize that cytokine over-production in periodontitis is associated with the hyper acetylation of histones. Methods: Periodontitis and healthy subjects who need periodontal surgeries (pocket reduction for periodontitis patients or crown lengthening for healthy individuals) were enrolled under IRB approval. Gingival tissues from diseased and/or healthy sites were harvested during surgeries. Immunohistochemistry (IHC) staining was used to evaluate the expression of acetylated H3(K4+K9+K14+K18+K23+K27). The inflammatory status of tissues were assessed by immune cell infiltration level under Hematoxylin and eosin (H&E) staining. Subgingival plaques were collected and 16s rRNA sequencing was used to profile the microbiome. Results: 39 subjects were recruited for this study. 24 patients were included in the diseased group and 15 in the healthy group. Through IHC, H3 acetylation was detected in the nucleus of gingival epithelial cells, fibroblasts, endothelial cells and infiltration immune cells. In the connective tissues, a higher percentage score was seen in periodontitis samples although it was not statistically significant (P=0.0521). There was no difference in the intensity score and total IHC score. Analyses based on tissue inflammatory status showed that the percentage score of acetylated H3 in inflamed tissues was dramatically higher than that in non-inflamed tissues, as well as well as the total IHC score. From 16s rRNA sequencing, 9 species differently presented between periodontitis and healthy pockets. Conclusion: Within the limitations of this study, a higher level of histone 3 acetylation was present in the inflamed gingival tissues compared to non-inflamed tissues. Our study suggested that histone acetylation may be a potential pharmacological target for treating periodontitis.
Rights
© Sarang Saadat
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-3-2023