DNA methylation profile of genes related to immune response in generalized periodontitis

Azevedo, Andréa Mara Oliveira; Rocha, Luiz Paulo Carvalho; Amormino, Simone Angélica de Faria; Gomes, Carolina Cavaliéri; Dutra, Walderez Ornelas; Gomez, Ricardo Santiago; Costa, José Eustáquio da; Moreira, Paula Rocha

doi:10.1111/jre.12726

Cited by 14 publications

(12 citation statements)

References 41 publications

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“…A prominent role in this context is attributed to epigenetic events, which induce changes in gene expression patterns without altering the DNA sequence [ 3 ]. These include DNA methylation, histone modification, chromatin remodelling and microRNA (miRNA) interference [ 4 , 5 ]. Epigenetic mechanisms play an important role in chronic inflammatory conditions, as observed in several diseases including cardiovascular disease, Alzheimer’s disease, rheumatoid arthritis and periodontal disease.…”

Section: Introductionmentioning

confidence: 99%

The Emerging Role of microRNA in Periodontitis: Pathophysiology, Clinical Potential and Future Molecular Perspectives

Santonocito

Polizzi

Palazzo

et al. 2021

IJMS

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During the last few decades, it has been established that messenger ribonucleic acid (mRNA) transcription does not inevitably lead to protein translation, but there are numerous processes involved in post-transcriptional regulation, which is a continuously developing field of research. MicroRNAs (miRNAs) are a group of small non-coding RNAs, which negatively regulate protein expression and are implicated in several physiological and pathological mechanisms. Aberrant expression of miRNAs triggers dysregulation of multiple cellular processes involved in innate and adaptive immune responses. For many years, it was thought that miRNAs acted only within the cell in which they were synthesised, but, recently, they have been found outside cells bound to lipids and proteins, or enclosed in extracellular vesicles, namely exosomes. They can circulate throughout the body, transferring information between cells and altering gene expression in the recipient cells, as they can fuse with and be internalised by the recipient cells. Numerous studies on miRNAs have been conducted in order to identify possible biomarkers that can be used in the diagnosis of periodontal disease. However, as therapeutic agents, single miRNAs can target several genes and influence multiple regulatory networks. The aim of this review was to examine the molecular role of miRNAs and exosomes in the pathophysiology of periodontal disease and to evaluate possible clinical and future implications for a personalised therapeutical approach.

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Section: Introductionmentioning

confidence: 99%

The Emerging Role of microRNA in Periodontitis: Pathophysiology, Clinical Potential and Future Molecular Perspectives

Santonocito

Polizzi

Palazzo

et al. 2021

IJMS

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“…15,16 In humans, research into epigenomic differences between patients with periodontal disease and periodontally healthy participants is limited and has focused mainly on candidate genes and epigenetic comparisons in gingival tissue. 17,18 Although the study of the epigenomic changes related to inflammatory process located at the periodontal tissue is very important to understand local inflammation in periodontitis, the tissue from a gingival biopsy with severe clinical inflammation and leukocyte infiltration would not be directly comparable with non-inflamed tissues in a periodontally healthy control subject, considering that the need of accounting for cellular heterogeneity in epigenetic studies has been largely demonstrated. 19,20 This problem can be approached via cell separation techniques; for example, Andia et al, using laser microdissection, separated epithelial and connective cell types in periodontal tissue making it possible to study DNA methylation differences in LINE1, SOCS1, and SOCS3.…”

Section: Introductionmentioning

confidence: 99%

ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome‐wide DNA methylation pilot study

Hernández

Hernández-Castañeda

Pieschacón

et al. 2021

J of Periodontal Research

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Objective: To investigate the differences in the epigenomic patterns of DNA methylation in peripheral leukocytes between patients with periodontitis and gingivally healthy controls evaluating its functional meaning by functional enrichment analysis. Background:The DNA methylation profiling of peripheral leukocytes as immunerelated tissue potentially relevant as a source of biomarkers between periodontitis patients and gingivally healthy subjects has not been investigated.Methods: A DNA methylation epigenome-wide study of peripheral leukocytes was conducted using the Illumina MethylationEPIC platform in sixteen subjects, eight diagnosed with periodontitis patients and eight age-matched and sex-matched periodontally healthy controls. A trained periodontist performed the clinical evaluation.Global DNA methylation was estimated using methylation-sensitive high-resolution melting in LINE1. Routine cell count cytometry and metabolic laboratory tests were also performed. The analysis of differentially methylated positions (DMPs) and differentially methylated regions (DMRs) was made using R/Bioconductor environment considering leukocyte populations assessed in both routine cell counts and using the FlowSorted.Blood.EPIC package. Finally, a DMP and DMR intersection analysis was performed. Functional enrichment analysis was carried out with the differentially methylated genes found in DMP.Results: DMP analysis identified 81 differentially hypermethylated genes and 21 differentially hypomethylated genes. Importantly, the intersection analysis showed that zinc finger protein 718 (ZNF718) and homeobox A4 (HOXA4) were differentially hypermethylated and zinc finger protein 57 (ZFP57) was differentially hypomethylated in periodontitis. The functional enrichment analysis found clearly immune-related ontologies such as "detection of bacterium" and "antigen processing and presentation." Conclusion:The results of this study propose three new periodontitis-related genes: ZNF718, HOXA4, and ZFP57 but also evidence the suitability and relevance of studying leukocytes' DNA methylome for biological interpretation of systemic immunerelated epigenetic patterns in periodontitis. | 711 HERNÁNDEZ Et al.

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“…There is now convincing evidence that epigenetic mechanisms such as DNA methylation are involved in the pathogenesis of periodontitis [9]. For example, it has been reported that tissue affected by periodontitis and normal periodontal tissue show differences in the methylation status of promoters for inflammation-related genes such as those encoding interleukin (IL)-8, tumor necrosis factor-alpha (TNFα) and toll-like receptor-2 (TLR2) [10][11][12][13]. Furthermore, increased methylation of the TLR2 promoter has been reported in a mouse model of periodontitis caused by infection with Porphyromonas gingivalis [7].…”

Section: Introductionmentioning

confidence: 99%

Decitabine Inhibits Bone Resorption in Periodontitis by Upregulating Anti-Inflammatory Cytokines and Suppressing Osteoclastogenesis

et al. 2021

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DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2′-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.

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DNA methylation profile of genes related to immune response in generalized periodontitis

Cited by 14 publications

References 41 publications

The Emerging Role of microRNA in Periodontitis: Pathophysiology, Clinical Potential and Future Molecular Perspectives

The Emerging Role of microRNA in Periodontitis: Pathophysiology, Clinical Potential and Future Molecular Perspectives

ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome‐wide DNA methylation pilot study

Decitabine Inhibits Bone Resorption in Periodontitis by Upregulating Anti-Inflammatory Cytokines and Suppressing Osteoclastogenesis

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