Periodontitis: Genomic instability implications and associated risk factors

Borba, Tatiana Thier de; Molz, Patrí­cia; Schlickmann, Diene da Silva; Santos, Caroline dos; Oliveira, Caio Fernando de; Prá, Daniel; Neto, Léo Kreather; Franke, Silvia Isabel Rech

doi:10.1016/j.mrgentox.2019.01.005

Cited by 15 publications

(19 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such changes promote increased cell invasion, proliferation, and seeding of metastatic tumor cells. Periodontitis severity is associated with increased DNA damage in the buccal mucosa, reflected by increased nuclear bud formation and chromosomal instability ( Borba et al., 2019 ). The role of periodontal disease in potentiation of OSCC was suggested in a murine model of OSCC induced by 4-nitroquinoline-1-oxide carcinogen, in which the size and number of cancerous lesions were increased upon co-infection with orally introduced periodontal pathogens, as opposed to germ-free mice that received carcinogen treatment alone ( Stashenko et al., 2019 ).…”

Section: It’s a Two-way Street: The Roles Of Oral Health In Systemic Health And Vice Versamentioning

confidence: 99%

Periodontal Disease: The Good, The Bad, and The Unknown

Sedghi

Bacino

Kapila

2021

Front. Cell. Infect. Microbiol.

189

View full text Add to dashboard Cite

Periodontal disease is classically characterized by progressive destruction of the soft and hard tissues of the periodontal complex, mediated by an interplay between dysbiotic microbial communities and aberrant immune responses within gingival and periodontal tissues. Putative periodontal pathogens are enriched as the resident oral microbiota becomes dysbiotic and inflammatory responses evoke tissue destruction, thus inducing an unremitting positive feedback loop of proteolysis, inflammation, and enrichment for periodontal pathogens. Keystone microbial pathogens and sustained gingival inflammation are critical to periodontal disease progression. However, recent studies have revealed the importance of previously unidentified microbes involved in disease progression, including various viruses, phages and bacterial species. Moreover, newly identified immunological and genetic mechanisms, as well as environmental host factors, including diet and lifestyle, have been discerned in recent years as further contributory factors in periodontitis. These factors have collectively expanded the established narrative of periodontal disease progression. In line with this, new ideologies related to maintaining periodontal health and treating existing disease have been explored, such as the application of oral probiotics, to limit and attenuate disease progression. The role of systemic host pathologies, such as autoimmune disorders and diabetes, in periodontal disease pathogenesis has been well noted. Recent studies have additionally identified the reciprocated importance of periodontal disease in potentiating systemic disease states at distal sites, such as in Alzheimer’s disease, inflammatory bowel diseases, and oral cancer, further highlighting the importance of the oral cavity in systemic health. Here we review long-standing knowledge of periodontal disease progression while integrating novel research concepts that have broadened our understanding of periodontal health and disease. Further, we delve into innovative hypotheses that may evolve to address significant gaps in the foundational knowledge of periodontal disease.

show abstract

Section: It’s a Two-way Street: The Roles Of Oral Health In Systemic Health And Vice Versamentioning

confidence: 99%

Periodontal Disease: The Good, The Bad, and The Unknown

Sedghi

Bacino

Kapila

2021

Front. Cell. Infect. Microbiol.

189

View full text Add to dashboard Cite

show abstract

“…Furthermore, improvements in linker technology and conjugation chemistries and recent advances in bioorthogonal chemistry will avail complexed small molecule therapeutics in an on-demand fashion and rapidly close the gap toward human application (Devaraj 2018; Peplow 2019). Recent evidence demonstrates that periodontal disease alone causes genome instability (Borba et al 2019), and titanium particles, as they shed from periodontal implants, have been linked to genome instability as well (Coen et al 2003; Ponsford and Diekwisch 2020). Only further advances in periodontal research and precision dentistry will allow for an informed assessment of the risk-to-benefit ratios of surgical versus conservative versus drug-based periodontal therapies.…”

Section: Targeting Histone Methylation As a Strategy For The Treatmenmentioning

confidence: 99%

Histone Methylation: Achilles Heel and Powerful Mediator of Periodontal Homeostasis

et al. 2020

View full text Add to dashboard Cite

The packaging of DNA around nucleosomes exerts dynamic control over eukaryotic gene expression either by granting access to the transcriptional machinery in an open chromatin state or by silencing transcription via chromatin compaction. Histone methylation modification affects chromatin through the addition of methyl groups to lysine or arginine residues of histones H3 and H4 by means of histone methyl transferases or histone demethylases. Changes in histone methylation state modulate periodontal gene expression and have profound effects on periodontal development, health, and therapy. At the onset of periodontal development, progenitor cell populations such as dental follicle cells are characterized by an open H3K4me3 chromatin mark on RUNX2, MSX2, and DLX5 gene promoters. During further development, periodontal progenitor differentiation undergoes a global switch from the H3K4me3 active methyl mark to the H3K27me3 repressive mark. When compared with dental pulp cells, periodontal neural crest lineage differentiation is characterized by repressive H3K9me3 and H3K27me3 marks on typical dentinogenesis-related genes. Inflammatory conditions as they occur during periodontal disease result in unique histone methylation signatures in affected cell populations, including repressive H3K9me3 and H3K27me3 histone marks on extracellular matrix gene promoters and active H3K4me3 marks on interleukin, defensin, and chemokine gene promoters, facilitating a rapid inflammatory response to microbial pathogens. The inflammation-induced repression of chromatin on extracellular matrix gene promoters presents a therapeutic opportunity for the application of histone methylation inhibitors capable of inhibiting suppressive trimethylation marks. Furthermore, inhibition of chromatin coregulators through interference with key inflammatory mediators such as NF-kB by means of methyltransferase inhibitors provides another avenue to halt the exacerbation of the inflammatory response in periodontal tissues. In conclusion, histone methylation dynamics play an intricate role in the fine-tuning of chromatin states during periodontal development and harbor yet-to-be-realized potential for the treatment of periodontal disease.

show abstract

“…Genomic instability, such as microsatellite instability and chromosomal instability, is an enabling characteristic of most cancers that promotes tumor progression. A cross-sectional study showed that periodontitis could influence the DNA damage status, suggesting that oral microbiota may induce DNA damage and cause genome instability [ 99 ]. For example, A. actinomycetemcomitans infection can induce DNA double-strand breaks (DSBs) in host cells and subsequently increase the risk of tumorigenesis (Fig.…”

Section: Regulation Of Hallmarks Of Cancer By Oral Microbiotamentioning

confidence: 99%

Oral microbiota in the oral-genitourinary axis: identifying periodontitis as a potential risk of genitourinary cancers

Yuan

Fang

et al. 2021

Military Med Res

View full text Add to dashboard Cite

Periodontitis has been proposed as a novel risk factor of genitourinary cancers: although periodontitis and genitourinary cancers are two totally distinct types of disorders, epidemiological and clinical studies, have established associations between them. Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis. Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers. Therefore, oral microbiota provides the bridge between periodontitis and genitourinary cancers. We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers. We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer, and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

show abstract

Periodontitis: Genomic instability implications and associated risk factors

Cited by 15 publications

References 15 publications

Periodontal Disease: The Good, The Bad, and The Unknown

Periodontal Disease: The Good, The Bad, and The Unknown

Histone Methylation: Achilles Heel and Powerful Mediator of Periodontal Homeostasis

Oral microbiota in the oral-genitourinary axis: identifying periodontitis as a potential risk of genitourinary cancers

Contact Info

Product

Resources

About