Epigenetic findings in periodontitis in UK twins: a cross sectional study
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE121633 | GEO | 2018/11/25
REPOSITORIES: GEO
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Project description:Epigenetic findings in periodontitis in UK twins: a cross sectional study
| PRJNA497900 | ENA
Project description:BackgroundGenetic 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.MethodsSelf-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.ResultsEpigenome-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.ConclusionsEpigenome-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:Objective Ulcerative colitis (UC) is a risk factor of periodontitis. This study aimed to investigate whether hematopoietic stem and progenitor cells (HSPCs) and their myeloid progeny exacerbate periodontal inflammation in UC. Design Ligature-induced periodontitis (LIP) was established in dextran sulfate sodium (DSS)-induced colitis (DIC) C57BL/6 mice. The bone resorption, intestinal and periodontal inflammation were evaluated by micro-CT and histological analyses. Inflammatory cytokines and lipopolysaccharide (LPS) in serum and gut microbiota were assessed by multiplexed flow cytometric assay, ELISA and 16S rRNA sequencing, respectively. Flow cytometry was performed to analyze HSPCs differentiation, and to sort hematopoietic stem cells for transcriptomic analysis. Berberine treatment of DIC was employed to investigate whether dampening of DIC would alleviate periodontitis. Results DIC mice exhibited disrupted intestinal barrier with dysbiotic gut microbiota, corroborating the elevated serum level of LPS and IL-1. Compared to DIC-free/LIP mice, DIC/LIP mice showed aggravated alveolar bone resorption, with enrichment of neutrophils extracellular traps (NETs) in periodontal tissues. DIC promoted myelopoiesis of HSPCs by up-regulating myeloid differentiation pathway. Intragastric administration of berberine dampened DIC and rescued the myeloid skewing of HSPCs, consequently alleviating periodontal destruction. Intriguingly, LIP induction after DIC remission still exhibited aggravated periodontal destruction and myeloid skewing of HSPCs, indicating a UC-trained immunity against periodontal infection. Conclusion Increased gut permeability and microbial dysbiosis in UC elevate the serum level of LPS and IL-1, inducing myeloid skewing of HSPCs with an immune memory. Generation of inflammatory potential myeloid cells causes NETs accumulation and aggravates periodontal destruction in the UC-related periodontitis.
2023-12-10 | GSE249582 | GEO
Project description:Periodontitis (PD) as a chronic inflammatory disease instigated by periodontal pathogenic bacteria and mediated by the host immune response, resulting in the destruction of supporting periodontal tissue and tooth loss in adults. Constructing an injectable delivery system that allows for sustained drug release within periodontal pockets to continuously eliminate pathogenic bacteria, reduce periodontal inflammation, and promote periodontal tissue regeneration is an effective strategy for periodontitis treatment. Here, we explore the therapeutic potential and underlying mechanisms of curcumin-loaded Pickering emulsion (PE-CUR) in periodontitis treatment. The Pickering emulsion formulation offers an effective delivery system, enhancing curcumin's bioavailability and therapeutic efficacy. In vitro studies, we demonstrate that the PE-CUR exhibit excellent biocompatibility and anti-inflammatory property by elimination of reactive oxygen species (ROS). In addition, PE-CUR significantly eliminate key periodontal pathogens, including Porphyromonas gingivalis (P. gingivalis) and Staphylococcus aureus (S. aureus). In a rat model of periodontitis, PE-CUR significantly attenuates periodontal tissue inflammation and alveolar bone loss, indicating a protective effect against periodontal tissue destruction. Mechanistically, PE-CUR promotes the expression of anti-inflammatory factors and inhibits the release of pro-inflammatory factors by regulating macrophage polarization from M1 to M2 and modulating the MAPK and PI3K-AKT signaling pathway. Furthermore, PE-CUR decreases the formation of osteoclasts as well as stimulates the activation and differentiation of osteoblasts successively, thereby ameliorating the periodontal inflammation and promoting the alveolar bone regeneration. Overall, our findings elucidate the therapeutic mechanisms of PE-CUR in periodontitis, suggesting its potential as a promising treatment strategy warranting further clinical investigation.
2024-08-16 | GSE274645 | GEO
Project description:Hypoxia has a significant impact on periodontal homeostasis and is a contributing factor to periodontal pathogenicity. This study aimed to investigate the role and mechanism of hypoxia in periodontitis.
2024-04-28 | GSE262663 | GEO
Project description:We performed single-cell RNA-sequencing analysis on mouse periodontal lesions to analyze the detailed mechanism underlying immune–bone cell interactions in periodontitis.
2024-03-06 | GSE254766 | GEO
Project description:Background/purpose Periodontal diseases exacerbate hepatic inflammation and diseases like non-alcoholic fatty liver disease via circulating pathogenic factors from periodontal tissue. Long-term pre-symptomatic state eventually leads to the development of such hepatic diseases. However, it is uncertain if periodontitis contributes in the onset of hepatic pre-symptomatic state. Herein, we conducted a hepatic whole transcription analysis of periodontitis-affected mice and healthy mice to understand the early functional changes in the hepatic system in periodontitis-affected mice. Materials and methods Silk ligatures were tied around mice second maxillary molars for 14 days to develop periodontitis. RNA-seq samples were collected from periodontal tissues and liver tissues of mice with periodontitis and healthy mice. Lipidomic analysis of hepatic omega-3 fatty acids in periodontitis-affected and healthy mice was conducted. The anti-inflammatory effects of omega-3 fatty acids and their metabolites were elucidated using hepatocytes HepG2 cells. Results In the liver of mice with periodontitis, genes coding for cytochrome P450 such as Cyp4a12a and Cyp4a12b were identified as significantly down-regulated genes. Lipidomic analyses identified that epoxidation and subsequent hydrolysis of hepatic omega-3 fatty acids were inhibited in periodontitis-affected mice. Eicosapentaenoic acid metabolites, epoxy eicosatetraenoic acid and dihydroxyeicosatetraenoic acid, inhibited inflammatory responses of HepG2 cells. Conclusion These results suggest that, in the liver of periodontitis-affected mice, due to the reduced activity of omega-3 fatty acid epoxidation, pre-symptomatic state with pro-inflammatory status develop. Therefore, early intervention of periodontitis might contribute to the prevention of the onset of hepatic diseases.
2024-05-03 | GSE264546 | GEO
Project description:Inflammatory periodontal disease (periodontitis) is widespread in dogs. This study aimed to evaluate site-specific changes in the canine gingival crevicular fluid (GCF) proteome during the longitudinal progression from very mild gingivitis to mild periodontitis. Periodontitis diagnosis in dogs requires anaesthesia, our ultimate aim was to develop a periodontitis diagnostic that could be applied to samples taken from conscious dogs. The objective of this work was to identify potential biomarkers of periodontal disease progression in the GCF of dogs.
2016-03-21 | PXD003337 | Pride
Project description:Periodontitis is a chronic inflammatory disease resulting from a dysbiosis of the dental biofilm and a dysregulated host response in susceptible individuals. It is characterized by periodontal attachment destruction, bone resorption, and eventual tooth loss. Salivary biomarkers have been sought to predict and prevent periodontitis. This comparative study analyzed the salivary proteome of 30 individuals with chronic periodontitis (CP) and 10 with periodontal health (PH), and correlated specific proteins with clinical parameters of disease by using mass spectrometry. Stimulated whole saliva was obtained and pooled for 5 healthy controls and 15 CP patients, precipitated with TCA, digested enzymatically with trypsin and analyzed by an LTQ Orbitrap Velos equipped with a nanoelectrospray ion source. A wide range of salivary proteins of various functions was significantly reduced in CP individuals, whereas salivary acidic proline-rich phosphoprotein, submaxillary gland androgen-regulated protein, histatin, fatty acid-binding protein, thioredoxin, and cystatin were predominant in diseased patients and correlated significantly with signs of periodontal attachment loss and inflammation. Specific salivary proteins were associated with PH and CP. These differences in salivary proteome profiles may contribute to the identification of disease indicators or signatures and the improvement of periodontal diagnosis.
2020-05-20 | PXD015024 | Pride
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