Periodontitis is a chronic multifactorial inflammatory disease associated with microbial dysbiosis and characterized by progressive destruction of the periodontal tissues. Such chronic infectious ...inflammatory disease is recognized as a major public health problem worldwide with measurable impact in systemic health. It has become evident that the periodontal disease phenotypes are not only determined by the microbiome effect, but the extent of the tissue response is also driven by the host genome and epigenome patterns responding to various environmental exposures. More recently there is mounting evidence indicating that epigenetic reprogramming in response to combined intrinsic and environmental exposures, might be particularly relevant due its plasticity and potential application towards precision health. The complex epigenetic crosstalk is reflected in the prognosis and progress of periodontal diseases and may also lead to a favorable landscape for cancer development. This review discusses epigenomics modifications focusing on the role of DNA methylation and pathways linking microbial infection and inflammatory pathways, which are also associated with carcinogenesis. There is a more clear vision whereas 'omics' technologies applied to unveil relevant epigenetic factors could play a significant role in the treatment of periodontal disease in a personalized mode, evidencing that public health approach should coexist with precision individualized treatment.
Zhang S, Crivello A, Offenbacher S, Moretti A, Paquette DW, Barros SP. Interferon‐gamma promoter hypomethylation and increased expression in chronic periodontitis. J Clin Periodontol current year ...2010; 37: 953–961. doi: 10.1111/j.1600‐051X.2010.01616.x.
Aim: The goal of this investigation was to determine whether epigenetic modifications in the IFNG promoter are associated with an increase of IFNG transcription in different stages of periodontal diseases.
Materials and Methods: DNA was extracted from gingival biopsy samples collected from 47 total sites from 47 different subjects: 23 periodontally healthy sites, 12 experimentally induced gingivitis sites and 12 chronic periodontitis sites. Levels of DNA methylation within the IFNG promoter containing six CpG dinucleotides were determined using pyrosequencing technology. Interferon gamma mRNA expression was analysed by quantitative polymerase chain reactions using isolated RNA from part of the biological samples mentioned above.
Results: The methylation level of all six analysed CpG sites within the IFNG promoter region in the periodontitis biopsies {52% interquartile range, IQR (43.8%, 63%)} was significantly lower than periodontally healthy samples {62% IQR (51.3%, 74%), p=0.007} and gingivitis biopsies {63% IQR (55%, 74%), p=0.02}. The transcriptional level of IFNG in periodontitis biopsies was 1.96‐fold and significantly higher than tissues with periodontal health (p=0.04). Although the mRNA level from experimental gingivitis samples exhibited an 8.5‐fold increase as compared with periodontally healthy samples, no significant methylation difference was observed in experimental gingivitis sample.
Conclusions: A hypomethylation profile within IFNG promoter region is related to an increase of IFNG transcription present in the chronic periodontitis biopsies, while such an increase of IFNG in experimentally induced gingivitis seems independent of promoter methylation alteration.
Responses to biotic stress in plants lead to dramatic reprogramming of gene expression, favoring stress responses at the expense of normal cellular functions. Transcription factors are master ...regulators of gene expression at the transcriptional level, and controlling the activity of these factors alters the transcriptome of the plant, leading to metabolic and phenotypic changes in response to stress. The functional analysis of interactions between transcription factors and other proteins is very important for elucidating the role of these transcriptional regulators in different signaling cascades. In this review, we present an overview of protein-protein interactions for the six major families of transcription factors involved in plant defense: basic leucine zipper containing domain proteins (bZIP), amino-acid sequence WRKYGQK (WRKY), myelocytomatosis related proteins (MYC), myeloblastosis related proteins (MYB), APETALA2/ ETHYLENE-RESPONSIVE ELEMENT BINDING FACTORS (AP2/EREBP) and no apical meristem (NAM), Arabidopsis transcription activation factor (ATAF), and cup-shaped cotyledon (CUC) (NAC). We describe the interaction partners of these transcription factors as molecular responses during pathogen attack and the key components of signal transduction pathways that take place during plant defense responses. These interactions determine the activation or repression of response pathways and are crucial to understanding the regulatory networks that modulate plant defense responses.
Background: Few studies have examined the potential effects of periodontal treatment during pregnancy on pregnancy outcomes, periodontal status, and inflammatory biomarkers.
Methods: A randomized, ...delayed‐treatment, controlled pilot trial was conducted to evaluate the effects of second‐trimester scaling and root planing and the use of a sonic toothbrush on the rate of preterm delivery (<37 weeks gestation). Secondary outcome measures included changes in periodontal status, levels of eight oral pathogens, levels of gingival crevicular fluid (GCF) interleukin‐1β (IL‐1β), prostaglandin E2 (PGE2), 8‐isoprostane (8‐iso), and IL‐6, and serum levels of IL‐6, soluble intercellular adhesion molecule 1 (sICAM1), 8‐isoprostane, soluble glycoprotein 130 (sGP130), IL‐6 soluble receptor (IL‐6sr), and C‐reactive protein (CRP). Logistic regression models were used to test for effects of treatment on preterm delivery. Secondary outcomes were analyzed by analysis of covariance adjusting for subject baseline values.
Results: Periodontal intervention resulted in a significantly decreased incidence odds ratio (OR) for preterm delivery (OR = 0.26; 9‐% confidence interval = 0.08 to 0.85), adjusting for baseline periodontal status which was unbalanced after randomization. Pregnancy without periodontal treatment was associated with significant increases in probing depths, plaque scores, GCF IL‐1β, and GCF IL‐6 levels. Intervention resulted in significant improvements in clinical status (attachment level, probing depth, plaque, gingivitis, and bleeding on probing scores) and significant decreases in levels of Prevotella nigrescens and Prevotella intermedia, serum IL‐6sr, and GCF IL‐1β.
Conclusions: Results from this pilot study (67 subjects) provide further evidence supporting the potential benefits of periodontal treatment on pregnancy outcomes. Treatment was safe, improved periodontal health, and prevented periodontal disease progression. Preliminary data show a 3.8‐fold reduction in the rate of preterm delivery, a decrease in periodontal pathogen load, and a decrease in both GCF IL‐1β and serum markers of IL‐6 response. However, further studies will be needed to substantiate these early findings.
Increasing evidence suggests that maternal gingivitis and periodontitis may be a risk factor for preterm birth and other adverse pregnancy outcomes.
To clarify the possible mechanisms behind the ...association between periodontal disease and preterm delivery, the authors reviewed studies of the effect of infection with periodontal pathogens in animal models on pregnancy outcomes including fetal growth, placental structural abnormalities and neonatal health. After the first report, in 1996, of a potential association between maternal periodontal disease and delivery of a preterm/low-birth-weight infant in humans, many case control and prospective studies were published. This review summarizes these, as well as early studies involving periodontal intervention to reduce risk.
Although there are some conflicting findings and potential problems regarding uncontrolled underlying risk factors, most of the clinical studies indicate a positive correlation between periodontal disease and preterm birth. Recent studies also have shown that there are microbiologic and immunological findings that strongly support the association. The studies indicate that periodontal infection can lead to placental-fetal exposure and, when coupled with a fetal inflammatory response, can lead to preterm delivery. Data from animal studies raise the possibility that maternal periodontal infections also may have adverse long-term effects on the infant's development.
Education for patients and health care providers regarding the biological plausibility of the association and the potential risks is indicated, but there is insufficient evidence at this time for health care policy recommendations to provide maternal periodontal treatments for the purpose of reducing the risk of adverse pregnancy outcomes.
Type 2 Diabetes Mellitus (T2DM) and Periodontitis (P) are prevalent multifactorial disorders worldwide, sharing a bidirectional relationship influenced by the genetic susceptibility of the host ...immune system. We investigated whether SNPs in the Interleukin 8 (IL8, alias CXCL8) gene could be associated with T2DM and Periodontitis.
Genomic DNA was obtained from 874 Brazilian individuals divided into: Healthy group (n = 307), Periodontitis group (n = 334), and individuals affected by both T2DM and Periodontitis (T2DM_P) group (n = 233). The SNPs −251(T>A) rs4073, +396(T>G) rs2227307 and +781(C>T) rs2227306 were genotyped by TaqMan®. Multiple logistic regressions were used to determine the degree of association between polymorphisms (and haplotypes) with periodontitis and T2DM adjusted for known confounders.
The additive model revealed that the heterozygous AT(-251), GT(+396) and CT(+781) genotypes showed a lower risk for the diseased phenotypes, and carriers of the TTC/TTC haplotype were significantly susceptible to T2DM and Periodontitis concomitantly, as well to isolated Periodontitis (mainly the severe form).
We concluded, for the first time, that these functional CXCL8 SNPs, and the homozygous TTC haplotype are relevant genetic factors for T2DM and Periodontitis as comorbidities, as well as for severe Periodontitis susceptibility in Brazilian population.
•Heterozygous rs4073, rs2227307 and rs2227306 show a protective effect for diseased phenotypes.•The TTC/TTC haplotype in the Interleukin 8 gene indicates susceptibility to Periodontitis.•The TTC/TTC haplotype in the Interleukin 8 gene increases the risk of T2DM and Periodontitis.
Salivary Biomarkers in a Biofilm Overgrowth Model Morelli, Thiago; Stella, Michael; Barros, Silvana P. ...
Journal of periodontology (1970),
December 2014, 2014-Dec, 2014-12-00, 20141201, Letnik:
85, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Background: The purpose of this study is to determine whether baseline salivary inflammatory biomarkers could discriminate between different clinical levels of disease and/or detect clinical changes ...over a 3‐week stent‐induced biofilm overgrowth (SIBO) period.
Methods: A total of 168 participants were enrolled in a 21‐day experimental gingivitis investigation and grouped according to clinical measures of periodontal status of health and diseased individuals representing each of five biofilm gingival interface (BGI) periodontal groups: 1) health, all probing depth (PD) <3 mm and bleeding on probing (BOP) <10%; 2) gingivitis, all PD <3 mm and BOP ≥10%; 3) periodontitis (P)1, ≥1 site with PD >3 mm and BOP ≤10%; 4) P2, ≥1 site with PD >3 mm and BOP >10% but ≤50%; and 5) P3, ≥1 site with PD >3 mm and BOP >50%. Stents were used to prevent plaque removal during brushing over one maxillary and one mandibular posterior dental sextant for 21 days. Clinical periodontal parameters and unstimulated saliva were collected at screening, baseline, and each week during SIBO. Saliva samples were assessed for levels of 13 different biomarkers by multiplex immunoassay.
Results: Higher salivary levels of interleukin (IL)‐1β, matrix metalloproteinase (MMP)‐3, MMP‐8, MMP‐9, and neutrophil gelatinase‐associated lipocalin (NGAL) were found in diseased groups compared with the healthy group at baseline. Conversely, higher IL‐1 receptor antagonist (ra) levels were found in healthy patients at baseline. In addition, during SIBO, MMP‐1, tissue inhibitor of metalloproteinase (TIMP)‐1, and TIMP‐2 levels increased across all participant groups. A stepwise linear regression model using all salivary biomarkers demonstrated that, at baseline, increased IL‐1ra (P = 0.004) and IL‐6 (P = 0.009) were significantly associated with change in PDs during SIBO.
Conclusions: In summary, this investigation supports salivary levels of IL‐1ra and IL‐6 as potential indicators for PD changes during induced gingival inflammation. In addition, participants from the BGI‐P3 group (severe periodontitis) demonstrated elevated baseline levels of IL‐1β, MMP‐3, MMP‐8, MMP‐9, and NGAL compared with the other study groups, strengthening the relevance of participants’ biologic phenotype on expression of salivary biomarkers.
To evaluate if treating maternal periodontal disease, a pro-inflammatory condition, during pregnancy (intervention) compared to after pregnancy (control) reduces the likelihood of offspring screening ...positive for autism spectrum disorder (ASD).
In a follow-up study to the MOTOR randomized trial, we compared rates of positive screens on the Modified Checklist for Autism in Toddlers (M-CHAT) among n = 306 two-year-old toddlers and correlated findings to maternal and cord blood pro-inflammatory interleukin-6 (IL-6).
Toddlers in the intervention group had decreased risk of a positive M-CHAT screen (adjusted RR = 0.53, 95% CI 0.29-0.99). Toddlers screening positive compared to negative had higher mean IL-6 in cord blood (1.58 ± 1.14 vs. 1.09 ± 0.72 p = 0.001) and maternal IL-6 change from baseline (1.30 ± 0.61 vs 0.96 ± 0.62 p = 0.03).
Treating periodontal disease during pregnancy reduced risk of a positive ASD screen. M-CHAT positivity was associated with increased IL-6 in maternal and cord blood.
Trial Registration numbers: Clinicaltrials.gov NCT03423836.
Background Periodontitis is a novel risk factor for inflammation and cardiovascular disease in the dialysis population. Limited information exists about the impact of periodontal therapy in patients ...receiving dialysis. Study Design Randomized controlled trial to assess feasibility and gather preliminary data. Setting & Participants Dialysis patients with moderate/severe chronic periodontitis. Intervention Intensive treatment, consisting of scaling and root planing, extraction of hopeless teeth, and placement of local-delivery antibiotics, was performed at the baseline visit for treatment-group patients and after study completion for control-group patients. Outcomes Outcomes were feasibility (screening, recruitment, enrollment, adverse events, and study withdrawal/completion), clinical periodontal parameters (probing depth, clinical attachment level, bleeding on probing, gingival index, and plaque index), and serum albumin and interleukin 6 levels at 3 and 6 months postintervention. Results 342 dialysis patients were approached for participation: 53 were randomly assigned, with 26 participants assigned to immediate treatment and 27 assigned to a control arm for treatment after 6 months. 51 patients completed baseline appointments; 46 were available for 3-month follow-up, 45 were available for 6-month follow-up examinations, and 43 completed all visits. At 3 months, there was a statistically significant improvement for the treatment group compared to the control group for 3 periodontal parameters: mean probing depth ( P = 0.008), extent of probing depth ≥4 mm ( P = 0.02), and extent of gingival index ≥1 ( P = 0.01). However, by 6 months, the difference between groups was no longer present for any variable except probing depth ≥4 mm ( P = 0.04). There was no significant difference between groups for serum albumin or high-sensitivity interleukin 6 level at any time when adjusted for body mass index, diabetic status, and plaque index. Limitations Small sample size and relatively healthy population, imbalance in diabetes. Conclusions This small trial demonstrates successful cooperation between dentists and nephrologists and successful recruitment, treatment, and retention of dialysis patients with periodontitis. Larger studies with longer follow-up are needed to determine whether treatment can improve markers of inflammation and morbidity.
Purpose
Denture stomatitis is a common condition manifested by inflammation of the oral mucous membrane beneath a denture. The objective of this study was to compare the transcriptome of human ...palatal mucosa with chronic oral stomatitis‐associated Candida albicans infection to that of healthy oral mucosa.
Materials and Methods
Oral palatal biopsies were obtained from 17 healthy and 15 C. albicans‐infected stomatitis subjects for whole transcriptome analyses. The presence of C. albicans was confirmed by cytology and cultivable methods. The clinical severity of the stomatitis was evaluated by the Newton Classification (Class II or III). For transcriptome analyses a false discovery rate (FDR) of <0.05 was used, and the effects of age, race, and gender were evaluated by principle component analysis (PCA). Specific differentially expressed genes identified by mRNA array data were confirmed by measurements of salivary protein expression using multiplex analyses.
Results
Microarray analysis of mRNA expression indicated that in C. albicans stomatitis there were 3034 genes‐in‐play that were differentially expressed and met the FDR < 0.05 criteria. Two hundred thirty five (235) genes were up‐regulated >2‐fold, and 71 genes were down‐regulated >2‐fold. Five of the 6 most significant gene ontology pathways involve inflammation and activation of the immune response with CD28 and CTLA signaling of T cells. There was strong up‐regulation of TLR2, CD14, MYD88, IKKA, and NFKB as the dominant toll‐like receptor‐signaling pathway. The expression of several extracellularly expressed inflammatory protein genes was up‐regulated in candidiasis, and 2 were confirmed as up‐regulated within the saliva using protein multiplexing analyses.
Conclusions
Neutrophil recruitment and activation, epithelial suppression, and T‐cell activation appear as major pathways in chronic oral candidiasis. Tissue up‐regulation of TLR2 pathways, as well as potential C. albicans binding proteins, was observed, whereas keratin and adhesion molecule synthesis were down‐regulated. Several candidate biomarkers to potentially identify the presence of oral candidiasis were differentially expressed in tissues and saliva.
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