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Epigenetics in Periodontal Disease Diagnosis, Systemic Interactions and Treatment
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Epigenetics in Periodontal Disease Diagnosis, Systemic Interactions and Treatment

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell and Gene Therapy".

Deadline for manuscript submissions: closed (15 January 2023) | Viewed by 12537

Special Issue Editors

Dr. Pingping Han

E-Mail Website
Guest Editor
1. Center for Oral-facial Regeneration, Rehabilitation and Reconstruction (COR3), The University of Queensland, Brisbane, QLD 4006, Australia
2. School of Dentistry, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD 4006, Australia
Interests: mechanotransduction; periodontal tissue engineering; extracellular vesicles; diagnostics
Prof. Dr. Saso Ivanovski

E-Mail Website
Guest Editor
Centre for Orofacial Regeneration, Reconstruction and Rehabilitation (COR3), School of Dentistry, The University of Queensland, 288 Herston Road, Herston, QLD 4006, Australia
Interests: periodontal disease treatment; biofabrication; periodontal tissue engineering; extracellular vesicles; regenerative medicine and dentistry
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Peter Mark Bartold

E-Mail Website
Guest Editor
School of Dentistry, The University of Adelaide, Adelaide, SA 5000, Australia
Interests: stem cell therapy; epigenetics drugs; periodontitis and rheumatoid arthritis; periodontal treatment; personalized and precision periodontics

Special Issue Information

Dear Colleagues,

Epigenetics is the study of reversible change in gene function through DNA/RNA methylation, histone modification, and non-coding RNAs resulting from environmental and behavioral factors. Although small non-coding RNAs are emerging as potential diagnostic and therapeutic agents for periodontal disease, little is known of the methylation and histone modification aspects of epigenetics in periodontitis and its interaction with systemic conditions.

Periodontitis is a chronic inflammatory disease associated with a dysbiotic plaque biofilm and characterized by the destruction of periodontal tissues. It shares common risk factors (environment and lifestyle) with other systemic diseases, such as cardiovascular disease, diabetes, arthritis, osteoporosis and neurodegenerative disease. The discovery of epigenetic biomarkers and therapeutics for periodontitis and periodontitis-associated diseases, control of oral microbial dysbiosis via epigenetic modulation, and epigenetic approaches for promoting periodontal regeneration remain limited. The epigenetic marks of histone, genetic material, microbial by-products, or in outer membrane and extracellular vesicles are likely to be mediated by periodontitis pathogenesis and, thus, are potential tools for diagnosis and therapy in the management of periodontal disease and its interaction with systemic diseases.

The purpose of this Special Issue is to bring together a broad scope of research and review papers in the field of epigenetics and periodontal disease, to highlight recent findings, and to develop approaches for the diagnosis and treatment of periodontitis and periodontitis-related systemic diseases.  

Dr. Pingping Han
Prof. Dr. Saso Ivanovski
Prof. Dr. Peter Mark Bartold
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Periodontitis
  • Periodontitis-associated systemic diseases (i.e., neurodegenerative disease, diabetes, osteoporosis)
  • Epigenetics
  • Extracellular vesicles and outer membrane vesicles
  • Diagnostics
  • Therapeutics
  • Periodontal tissue engineering
  • Periodontal regenerative medicine

Published Papers (4 papers)

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Research

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15 pages, 3622 KiB  
Article
Porphyromonas gingivalis-Derived Lipopolysaccharide Promotes Glioma Cell Proliferation and Migration via Activating Akt Signaling Pathways
by Zeyuan Gao, Xiuhong Weng, Donghu Yu, Zhiyong Pan, Mingjuan Zhao, Bo Cheng and Zhiqiang Li
Cells 2022, 11(24), 4088; https://doi.org/10.3390/cells11244088 - 16 Dec 2022
Cited by 2 | Viewed by 1485
Abstract
Periodontitis is significantly associated with the risk of cancers in the lung and the digestive system. Emerging evidence shows a plausible link between periodontitis and several types of brain diseases. However, the association between periodontal infection and glioma remains unclear. In the cultured [...] Read more.
Periodontitis is significantly associated with the risk of cancers in the lung and the digestive system. Emerging evidence shows a plausible link between periodontitis and several types of brain diseases. However, the association between periodontal infection and glioma remains unclear. In the cultured GL261 glioma cells, P. gingivalis lipopolysaccharide (LPS) significantly promoted cell proliferation at concentrations ranging from 10 to 1000 ng/mL. It promoted cell migration at a higher concentration (100 and 1000 ng/mL). Additionally, exposure to 100 ng/mL P. gingivalis LPS induced a significant increase in the expression of TNF-α, TGF-β, MMP2, and MMP9, as well as the phosphorylation level of Akt at Ser473. These changes induced by P. gingivalis LPS were significantly antagonized by the Akt inhibitor. Furthermore, a total of 48 patients with brain tumors were enrolled to investigate their periodontal status before receiving tumor management. Poor periodontal status [probing depth (PD) ≥ 6 mm and attachment loss (AL) >5 mm] was found in 42.9% (9/21) of patients with glioma, which was significantly higher than that in patients with benign tumors and the relevant data in the 4th National Oral Health Survey in China. The glioma patients with both AL > 5 mm and PD ≥ 6 mm had a higher ki-67 labeling index than those with AL ≤ 5 mm or PD < 6 mm. These findings support the association between periodontal infection and glioma progression. Full article
(This article belongs to the Special Issue Epigenetics in Periodontal Disease Diagnosis, Systemic Interactions and Treatment)
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20 pages, 3094 KiB  
Article
Osteogenic Commitment of Human Periodontal Ligament Cells Is Predetermined by Methylation, Chromatin Accessibility and Expression of Key Transcription Factors
by Rahyza I. F. Assis, Francesca Racca, Rogério S. Ferreira, Karina G. S. Ruiz, Rodrigo A. da Silva, Samuel J. H. Clokie, Malgorzata Wiench and Denise C. Andia
Cells 2022, 11(7), 1126; https://doi.org/10.3390/cells11071126 - 26 Mar 2022
Cited by 7 | Viewed by 2233
Abstract
Periodontal ligament stem cells (PDLCs) can be used as a valuable source in cell therapies to regenerate bone tissue. However, the potential therapeutic outcomes are unpredictable due to PDLCs’ heterogeneity regarding the capacity for osteoblast differentiation and mineral nodules production. Here, we identify [...] Read more.
Periodontal ligament stem cells (PDLCs) can be used as a valuable source in cell therapies to regenerate bone tissue. However, the potential therapeutic outcomes are unpredictable due to PDLCs’ heterogeneity regarding the capacity for osteoblast differentiation and mineral nodules production. Here, we identify epigenetic (DNA (hydroxy)methylation), chromatin (ATAC-seq) and transcriptional (RNA-seq) differences between PDLCs presenting with low (l) and high (h) osteogenic potential. The primary cell populations were investigated at basal state (cultured in DMEM) and after 10 days of osteogenic stimulation (OM). At a basal state, the expression of transcription factors (TFs) and the presence of gene regulatory regions related to osteogenesis were detected in h-PDLCs in contrast to neuronal differentiation prevalent in l-PDLCs. These differences were also observed under stimulated conditions, with genes and biological processes associated with osteoblast phenotype activated more in h-PDLCs. Importantly, even after the induction, l-PDLCs showed hypermethylation and low expression of genes related to bone development. Furthermore, the analysis of TFs motifs combined with TFs expression suggested the relevance of SP1, SP7 and DLX4 regulation in h-PDLCs, while motifs for SIX and OLIG2 TFs were uniquely enriched in l-PDLCs. Additional analysis including a second l-PDLC population indicated that the high expression of OCT4, SIX3 and PPARG TFs could be predictive of low osteogenic commitment. In summary, several biological processes related to osteoblast commitment were activated in h-PDLCs from the onset, while l-PDLCs showed delay in the activation of the osteoblastic program, restricted by the persistent methylation of gene related to bone development. These processes are pre-determined by distinguishable epigenetic and transcriptional patterns, the recognition of which could help in selection of PDLCs with pre-osteoblastic phenotype. Full article
(This article belongs to the Special Issue Epigenetics in Periodontal Disease Diagnosis, Systemic Interactions and Treatment)
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19 pages, 6109 KiB  
Article
Palmitate-Triggered COX2/PGE2-Related Hyperinflammation in Dual-Stressed PdL Fibroblasts Is Mediated by Repressive H3K27 Trimethylation
by Lisa Schuldt, Michael Reimann, Katrin von Brandenstein, Julia Steinmetz, Annika Döding, Ulrike Schulze-Späte, Collin Jacobs and Judit Symmank
Cells 2022, 11(6), 955; https://doi.org/10.3390/cells11060955 - 10 Mar 2022
Cited by 4 | Viewed by 2959
Abstract
The interrelationships between periodontal disease, obesity-related hyperlipidemia and mechanical forces and their modulating effects on the epigenetic profile of periodontal ligament (PdL) cells are assumed to be remarkably complex. The PdL serves as a connective tissue between teeth and alveolar bone and is [...] Read more.
The interrelationships between periodontal disease, obesity-related hyperlipidemia and mechanical forces and their modulating effects on the epigenetic profile of periodontal ligament (PdL) cells are assumed to be remarkably complex. The PdL serves as a connective tissue between teeth and alveolar bone and is involved in pathogen defense and the inflammatory responses to mechanical stimuli occurring during tooth movement. Altered inflammatory signaling could promote root resorption and tooth loss. Hyperinflammatory COX2/PGE2 signaling was reported for human PdL fibroblasts (HPdLFs) concomitantly stressed with Porphyromonas gingivalis lipopolysaccharides and compressive force after exposure to palmitic acid (PA). The aim of this study was to investigate the extent to which this was modulated by global and gene-specific changes in histone modifications. The expression of key epigenetic players and global H3Kac and H3K27me3 levels were quantitatively evaluated in dual-stressed HPdLFs exposed to PA, revealing a minor force-related reduction in repressive H3K27me3. UNC1999-induced H3K27me3 inhibition reversed the hyperinflammatory responses of dual-stressed PA cultures characterized by increased COX2 expression, PGE2 secretion and THP1 adhesion. The reduced expression of the gene encoding the anti-inflammatory cytokine IL-10 and the increased presence of H3K27me3 at its promoter-associated sites were reversed by inhibitor treatment. Thus, the data highlight an important epigenetic interplay between the different stimuli to which the PdL is exposed. Full article
(This article belongs to the Special Issue Epigenetics in Periodontal Disease Diagnosis, Systemic Interactions and Treatment)
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Review

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23 pages, 1408 KiB  
Review
The Relevance of DNA Methylation and Histone Modification in Periodontitis: A Scoping Review
by Andrew Liaw, Chun Liu, Sašo Ivanovski and Pingping Han
Cells 2022, 11(20), 3211; https://doi.org/10.3390/cells11203211 - 13 Oct 2022
Cited by 13 | Viewed by 5088
Abstract
Background: Periodontitis is a chronic inflammatory disease involving an interplay between bacteria, inflammation, host response genes, and environmental factors. The manifestation of epigenetic factors during periodontitis pathogenesis and periodontal inflammation is still not well understood, with limited reviews on histone modification with [...] Read more.
Background: Periodontitis is a chronic inflammatory disease involving an interplay between bacteria, inflammation, host response genes, and environmental factors. The manifestation of epigenetic factors during periodontitis pathogenesis and periodontal inflammation is still not well understood, with limited reviews on histone modification with periodontitis management. This scoping review aims to evaluate current evidence of global and specific DNA methylation and histone modification in periodontitis and discuss the gaps and implications for future research and clinical practice. Methods: A scoping literature search of three electronic databases was performed in SCOPUS, MEDLINE (PubMed) and EMBASE. As epigenetics in periodontitis is an emerging research field, a scoping review was conducted to identify the extent of studies available and describe the overall context and applicability of these results. Results: Overall, 30 studies were evaluated, and the findings confirmed that epigenetic changes in periodontitis comprise specific modifications to DNA methylation patterns and histone proteins modification, which can either dampen or promote the inflammatory response to bacterial challenge. Conclusions: The plasticity of epigenetic modifications has implications for the future development of targeted epi-drugs and diagnostic tools in periodontitis. Such advances could be invaluable for the early detection and monitoring of susceptible individuals. Full article
(This article belongs to the Special Issue Epigenetics in Periodontal Disease Diagnosis, Systemic Interactions and Treatment)
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