Epigenetic findings in periodontitis in UK twins: a cross sectional study
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PROVIDER: PRJNA497900 | ENA |
REPOSITORIES: ENA
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Project description:Genetic and environmental risk factors contribute to periodontal disease, but the underlying susceptibility pathways are not fully understood. Epigenetic mechanisms are malleable regulators of gene function that can change in response to genetic and environmental stimuli, thereby providing a potential mechanism mediating risk effects in periodontitis. The aim of this study is to identify epigenetic changes across tissues that are associated with periodontal disease.
2018-11-25 | GSE121633 | GEO
Project description:BACKGROUND:Genetic and environmental risk factors contribute to periodontal disease, but the underlying susceptibility pathways are not fully understood. Epigenetic mechanisms are malleable regulators of gene function that can change in response to genetic and environmental stimuli, thereby providing a potential mechanism for mediating risk effects in periodontitis. The aim of this study is to identify epigenetic changes across tissues that are associated with periodontal disease. METHODS:Self-reported gingival bleeding and history of gum disease, or tooth mobility, were used as indicators of periodontal disease. DNA methylation profiles were generated using the Infinium HumanMethylation450 BeadChip in whole blood, buccal, and adipose tissue samples from predominantly older female twins (mean age 58) from the TwinsUK cohort. Epigenome-wide association scans (EWAS) of gingival bleeding and tooth mobility were conducted in whole blood in 528 and 492 twins, respectively. Subsequently, targeted candidate gene analysis at 28 genomic regions was carried out testing for phenotype-methylation associations in 41 (tooth mobility) and 43 (gingival bleeding) buccal, and 501 (tooth mobility) and 556 (gingival bleeding) adipose DNA samples. RESULTS:Epigenome-wide analyses in blood identified one CpG-site (cg21245277 in ZNF804A) associated with gingival bleeding (FDR?=?0.03, nominal p value?=?7.17e-8) and 58 sites associated with tooth mobility (FDR?<?0.05) with the top signals in IQCE and XKR6. Epigenetic variation at 28 candidate regions (247 CpG-sites) for chronic periodontitis showed an enrichment for association with periodontal traits, and signals in eight genes (VDR, IL6ST, TMCO6, IL1RN, CD44, IL1B, WHAMM, and CXCL1) were significant in both traits. The methylation-phenotype association signals validated in buccal samples, and a subset (25%) also validated in adipose tissue. CONCLUSIONS:Epigenome-wide analyses in adult female twins identified specific DNA methylation changes linked to self-reported periodontal disease. Future work will explore the environmental basis and functional impact of these results to infer potential for strategic personalized treatments and prevention of chronic periodontitis.
| S-EPMC6375219 | biostudies-literature
Project description:Treatment of periodontitis in people with diabetes remains challenging. Diabetes-enhanced oxidative stress is a primary cause of aggravation of periodontitis. The present study aimed to investigate the therapeutic potential of thioredoxin-1 (TRX1), an essential endogenous antioxidant protein, in the management of periodontitis with diabetes, as well as its role in modulating osteogenic differentiation. Our findings indicated that the production of reactive oxygen species (ROS) was elevated, while the expression of TRX1 was significantly reduced in the periodontal tissues of periodontitis mice with diabetes. Furthermore, knockdown of TRX1 in periodontal ligament stem cells (PDLSCs) resulted in the inhibition of osteogenic differentiation through disrupting Wnt/β-catenin signal pathway. However, this inhibition was restored upon administration of recombinant human TRX1 (rhTRX1). Importantly, rhTRX1 treatment decreased ROS generation, activated Wnt/β-catenin signal pathway and considerably promoted the alveolar bone repair of periodontitis mice with diabetes. These findings highlighted the crucial protective role of TRX1 in periodontitis with diabetes and suggested that it may serve as a potential therapeutic target for refractory periodontitis associated with oxidative stress.
2023-09-06 | GSE235930 | GEO
Project description:Gene expression was quantified in LCL, skin and fat derived from a subset of Twins UK (N=156 LCL, N=160 skin, N=166 fat) using Illuminas whole genome expression array (HumanHT-12 version 3). Cis eQTL analysis was performed in each tissue, following by multiple analyses assessing the tissue-specificity of regulatory variation.
2011-02-03 | E-MTAB-522 | biostudies-arrayexpress
Project description:mRNA microarray profiling was performed on healthy gingival biopsies from nonhuman primates (NHPs) (between 3 and 23 years old, and periodontitis gingival biopsies from NHPs (12-22 years old)
2014-10-15 | E-MTAB-1977 | biostudies-arrayexpress
Project description:Neutrophil recruitment and activation are hallmarks of the prevalent inflammatory disease, periodontitis. However, the mechanisms by which neutrophils contribute to in inflammatory bone destruction remain unclear. Herein, we document that neutrophil extracellular traps (NETs) have a direct role in mediating inflammatory pathology. In an established animal model of periodontitis, we demonstrate that genetic or pharmacologic inhibition of NETs formation, or removal of NETs by DNase-Ⅰ, alleviates inflammatory bone loss in vivo. Investigating the mechanisms by which NETs drive periodontal inflammation, we find that extracellular histones have a direct role in disease progression. Consistent with findings in animal models, histones bearing classic NET-associated post-translational modifications are correlated with disease severity and are significantly elevated in local lesions and systemic circulation of patients with periodontitis. Our work reveals NETs-associated components as pathogenic mediators, potential biomarkers, and therapeutic targets for periodontitis.
2023-05-23 | GSE228021 | GEO
Project description:To identify gene expression profiles in those periodontitis-associated fibroblasts (PAFs) versus normal gingival fibroblasts to determine their molecular repertoire, and exploit it for therapeutic intervention. We collected RNA from 4 paired PAF and non PAF from patients with periodontitis
2015-03-11 | E-GEOD-66771 | biostudies-arrayexpress
Project description:This study evaluated the transcriptome of healthy gingival tissue in patients with a history of generalized aggressive periodontitis (GAgP) and chronic periodontitis (CP) and in subjects with no history of periodontitis (H), using microarray analysis.
2017-03-29 | GSE79705 | GEO