Maternal Salivary miR-423-5p Is Linked to Neonatal Outcomes and Periodontal Status in Cardiovascular-High-Risk Pregnancies.

Periodontal disease (PD) during pregnancy may trigger systemic inflammation, increasing the risk of developing cardiometabolic disease (CMD). As a consequence, PD may result in the activation of cellular and molecular pathways, affecting the disease course and pregnancy outcome. Although microRNAs (miRNAs) are considered ideal biomarkers for many diseases, few studies have investigated salivary miRNAs and their role in pregnancy or neonatal outcomes. In this study, we sought to investigate the associations between salivary miRNAs of pregnant women with oral diseases and their effects on neonatal outcomes. Eleven (n = 11) salivary miRNAs from a cohort of pregnant women with oral diseases (n = 32; oral health, H; gingivitis, G; and periodontitis, P) were detected using a previous profiling analysis with an FDR < 0.20 and a fold change (FC) < 0.5 or FC > 2 for the most highly expressed miRNAs. Spearman correlations were performed for 11 salivary microRNAs associated with oral-derived inflammation, which could affect neonatal outcomes during pregnancies at risk for cardiometabolic disease (CMD), defined by the presence of a high pregestational BMI. In addition, ROC curves demonstrated the diagnostic accuracy of the markers used. Upregulation of miR-423-5p expression and a decrease in miR-27b-3p expression were detected in the P-group (p < 0.05), and ROC analysis revealed the diagnostic accuracy of miR-423-5p for discriminating oral diseases, such as gingivitis versus periodontitis (P vs. G, AUC = 0.78, p < 0.05), and for discriminating it from the healthy oral cavity (P vs. H, AUC = 0.9, p < 0.01). In addition, miR-27b-3p and miR-622 were also able to discriminate the healthy group from the P-group (AUC = 0.8, p < 0.05; AUC = 0.8, p < 0.05). miR-483-5p was able to discriminate between the G-group (AUC = 0.9, p < 0.01) and the P-group (AUC = 0.8, p < 0.05). These data support the role of salivary miRNAs as early biomarkers for neonatal outcomes in pregnant women with periodontal disease at high risk for CMD and suggest that there is cross-talk between salivary miRNAs and subclinical systemic inflammation.

Six miRNA expressions in the saliva of smokers and non-smokers with periodontal disease.

BACKGROUND: It has been stated that microRNA (miRNA) plays an important role in development, homeostasis, and immune functions, and abnormal miRNA expression may cause faster disease progression. OBJECTIVE: The aim of this study was to determine miR-203, miR-142-3p, miR-146a, miR-146b, miR-155, and miR-29b gene expressions in the saliva of smokers and non-smokers with the periodontal disease before and after non-surgical periodontal therapy (NSPT). METHODS: A total of 90 individuals, 30 with periodontitis, 30 with gingivitis, and 30 periodontally healthy (control group), were included. These three groups were divided into subgroups as smoking and non-smoking individuals, with 15 people in each group. NSPT was applied to patients with periodontitis and gingivitis. Saliva samples and clinical parameters were obtained at baseline and repeated 6 weeks after NSPT. RESULTS: Saliva miR-203, miR-142-3p, miR-146a, miR-146b, and miR-155 gene expressions were significantly upregulated in patients with periodontal disease compared to the control group both in smokers and non-smokers, and also these miRNAs' gene expressions were significantly higher in the periodontitis group than in the gingivitis group at baseline (p < .05). A significant increase in saliva miR-142-3p expression was detected in all groups of smokers compared to non-smokers (p < .05). Although there was a decrease in salivary miRNAs gene expressions with the treatment, it was not statistically significant (p > .05). CONCLUSIONS: These results suggest that salivary miR-146a, miR-146b, miR142-3p, miR-155, and miR-203 gene expressions increased with the progression of periodontal disease, but unchanged after periodontal treatment. Moreover, smoking may contribute to an increase in the levels of salivary miR-142-3p in the periodontal health and disease.

Identification of Streptococcus sanguinis genes producing biofilm from gingivitis.

Streptococcus sanguinis is a teeth commensal frontier colonizer and among the most common species in the oral biofilm. Dental plaque, caries, and gingivitis/periodontitis are caused by dysbiosis of oral flora. A biofilm assay was developed to investigate biofilm formation in S. sanguinis using the microtiter plate, tube, and Congo red agar methods in order to identify causing bacteria and determine responsible genes. Three genes, including pur B, thr B, and pyre E, were suspected of playing a role in forming in vivo biofilms in S. sanguinis. The present study shows these genes to be responsible for increased biofilm formation in gingivitis patients.

Association of the CD14 -260C/T polymorphism with plaque-induced gingivitis depends on the presence of Porphyromonas gingivalis.

BACKGROUND: Plaque-induced gingivitis is the most prevalent periodontal disease associated with pathogenic biofilms. The host immune system responds to pathogens through pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and their co-receptor cluster of differentiation 14 (CD14). AIM: This study investigated the association between the functional polymorphism in the CD14 gene and the dental plaque microbiota in children with gingivitis. DESIGN: A total of 590 unrelated children (307 with plaque-induced gingivitis and 283 controls, aged 13-15 years) were enrolled in this case-control study. Dental plaque was processed using a ParoCheck® 20 detection kit. The CD14 -260C/T (rs2569190) polymorphism was determined with the PCR-RFLP method. RESULTS: Gingivitis was detected in 64.2% of boys and 35.8% of girls (P < .001). Children with gingivitis had a significantly higher occurrence of dental caries (P < .001). No significant differences in the CD14 -260C/T allele and genotype distribution among individuals with or without gingivitis in the whole cohort were found. Children with gingivitis and P gingivalis, however, were significantly more frequent carriers of the CT and TT genotypes than children with gingivitis without P gingivalis or healthy controls (P < .05). CONCLUSIONS: The CD14 -260C/T polymorphism acts in cooperation with P gingivalis to trigger plaque-induced gingivitis in Czech children.

Differential DNA methylation and mRNA transcription in gingival tissues in periodontal health and disease.

AIM: We investigated differential DNA methylation in gingival tissues in periodontal health, gingivitis, and periodontitis, and its association with differential mRNA expression. MATERIALS AND METHODS: Gingival tissues were harvested from individuals and sites with clinically healthy and intact periodontium, gingivitis, and periodontitis. Samples were processed for differential DNA methylation and mRNA expression using the IlluminaEPIC (850 K) and the IlluminaHiSeq2000 platforms, respectively. Across the three phenotypes, we identified differentially methylated CpG sites and regions, differentially expressed genes (DEGs), and genes with concomitant differential methylation at their promoters and expression were identified. The findings were validated using our earlier databases using HG-U133Plus2.0Affymetrix microarrays and Illumina (450 K) methylation arrays. RESULTS: We observed 43,631 differentially methylated positions (DMPs) between periodontitis and health, and 536 DMPs between gingivitis and health (FDR < 0.05). On the mRNA level, statistically significant DEGs were observed only between periodontitis and health (n = 126). Twelve DEGs between periodontitis and health (DCC, KCNA3, KCNA2, RIMS2, HOXB7, PNOC, IRX1, JSRP1, TBX1, OPCML, CECR1, SCN4B) were also differentially methylated between the two phenotypes. Spearman correlations between methylation and expression in the EPIC/mRNAseq dataset were largely replicated in the 450 K/Affymetrix datasets. CONCLUSIONS: Concomitant study of DNA methylation and gene expression patterns may identify genes whose expression is epigenetically regulated in periodontitis.

Tumour necrosis factor-alpha polymorphism -308 G/a and its protein in subjects with gingivitis.

OBJECTIVE: This study examined the association between tumour necrosis factor-alpha (TNF- α) (-308 G/A) polymorphism and gingivitis, and serum and salivary TNF- α levels, in a Mexican population. MATERIAL AND METHODS: This study enrolled 171 subjects, divided into two groups: healthy subjects and gingivitis patients. TNF- α (-308 G/A) gene polymorphism was analyzed by PCR-RFLP assay. Salivary and serum samples were used to measure cytokine levels through the ELISA technique. RESULTS: TNF- α (-308 G/A) polymorphism was shown to have a protective effect in carriers of the A/A genotype and allele A. The G/A genotype is associated with an increase in high-density lipoprotein cholesterol (HDL-C) levels in the gingivitis group. Healthy individuals had higher levels of salivary TNF- α and HDL-C, and increased salivary flow. Triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels were increased in the gingivitis group. No statistical differences were found in serum TNF- α levels. CONCLUSION: Our data demonstrate that the TNF- α -308 A/A genotype exerts a protective effect against gingivitis. Moreover, oral conditions are associated with some biochemical parameters.

Genetic polymorphisms in interleukin-6 and interleukin-1-beta were associated with dental caries and gingivitis.

OBJECTIVE: Evaluate the association between single nucleotide polymorphisms (SNPs) in Interleukin-6 (IL-6) gene (rs1800795) and in Interleukin-1-beta (IL-1ß) gene (rs1143627 and rs1143629) with dental caries and gingivitis in Brazilian children. MATERIAL AND METHODS: Three hundred and fifty-three children aged 8-11 years were included. Visible biofilm and gingival bleeding were evaluated by Community Periodontal Index. The International System for Detection and Assessment of Carious Lesions (ICDAS) was used to investigate dental caries. Real-time PCR evaluated SNPs in the DNA. Chi-square test, haplotype analysis and logistic regression were applied (alpha of 5%). RESULTS: The GG genotype in rs1800795 (IL-6) decreases the risk of gingivitis in a co-dominant model (p = .05; OR = 0.64). The GG genotype in rs1143627 (IL-1ß) reduces the risk of dental caries (Co-dominant model: ICDAS0 versus ICDAS1-6: p = .05; OR = 0.55. ICDAS0-2 versus ICDAS3-6: p = .02; OR = 0.49. Recessive model: ICDAS0 versus ICDAS1-6: p = .005; OR = 0.48. ICDAS0-2 versus ICDAS3-6: p = .004; OR = 0.45. Logistic regression: ICDAS0-2 versus ICDAS3-6: p = .05; OR = 0.24; CI 95%= 0.05-1.00). The GG genotype in rs1143629 was more frequent in ICDAS0 (p = .05; OR: 0.60). In the haplotype analysis, IL-1ß was associated with gingivitis. CONCLUSION: The rs1800795 in IL-6 gene was associated with gingivitis. The rs1143627 and rs1143629 in IL-1ß were associated with dental caries and gingivitis.

Interplay Between the Host, the Human Microbiome, and Drug Metabolism.

The human microbiome is composed of four major areas including intestinal, skin, vaginal, and oral microbiomes, with each area containing unique species and unique functionalities. The human microbiome may be modulated with prebiotics, probiotics, and postbiotics to potentially aid in the treatment of diseases like irritable bowel syndrome, bacterial vaginosis, atopic dermatitis, gingivitis, obesity, or cancer. There is also potential for many of the inhabitants of the human microbiome to directly modulate host gene expression and modulate host detoxifying enzyme activity like cytochrome P450s (CYPs), dehydrogenases, and carboxylesterases. Therefore, the microbiome may be important to consider during drug discovery, risk assessment, and dosing regimens for various diseases given that the human microbiome has been shown to impact host detoxification processes.

Salivary Small Extracellular Vesicles Associated miRNAs in Periodontal Status-A Pilot Study.

This pilot study aims to investigate whether salivary small extracellular vesicle (sEV)-associated microRNAs could act as potential biomarkers for periodontal disease status. Twenty-nine participants (10 who were healthy, nine with gingivitis, 10 with stage III/IV periodontitis) were recruited and unstimulated whole saliva samples were collected. Salivary sEVs were isolated using the size-exclusion chromatography (SEC) method and characterised by morphology, EV-protein and size distribution using transmission electron microscopy (TEM), Western Blot and Nanoparticle Tracking Analysis (NTA), respectively. Ten mature microRNAs (miRNAs) in salivary sEVs and saliva were evaluated using RT-qPCR. The discriminatory power of miRNAs as biomarkers in gingivitis and periodontitis versus healthy controls was evaluated by Receiver Operating Characteristics (ROC) curves. Salivary sEVs were comparable to sEVs morphology, mode, size distribution and particle concentration in healthy, gingivitis and periodontitis patients. Compared to miRNAs in whole saliva, three significantly increased miRNAs (hsa-miR-140-5p, hsa-miR-146a-5p and hsa-miR-628-5p) were only detected in sEVs in periodontitis when compared to that of healthy controls, with a good discriminatory power (area under the curve (AUC) = 0.96) for periodontitis diagnosis. Our study demonstrated that salivary sEVs are a non-invasive source of miRNAs for periodontitis diagnosis. Three miRNAs that are selectively enriched in sEVs, but not whole saliva, could be potential biomarkers for periodontal disease status.

Detection of Salivary Small Extracellular Vesicles Associated Inflammatory Cytokines Gene Methylation in Gingivitis.

Salivary small extracellular vesicles (sEV) are emerging as a potential liquid biopsy for oral diseases. However, technical difficulties for salivary sEV isolation remain a challenge. Twelve participants (five periodontally healthy, seven gingivitis patients) were recruited and salivary sEV were isolated by ultracentrifuge (UC-sEV) and size exclusion chromatography (SEC-sEV). The effect of UC and SEC on sEV yield, DNA methylation of five cytokine gene promoters (interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1ß, IL-8, and IL-10), and functional uptake by human primary gingival fibroblasts (hGFs) was investigated. The results demonstrated that SEC-sEV had a higher yield of particles and particle/protein ratios compared to UC-sEV, with a minimal effect on the detection of DNA methylation of five cytokine genes and functional uptake in hGFs (n = 3). Comparing salivary sEV characteristics between gingivitis and healthy patients, gingivitis-UC-sEV were increased compared to the healthy group; while no differences were found in sEV size, oral bacterial gDNA, and DNA methylation for five cytokine gene promoters, for both UC-sEV and SEC-sEV. Overall, the data indicate that SEC results in a higher yield of salivary sEV, with no significant differences in sEV DNA epigenetics, compared to UC.

Keratinocyte-specific ablation of protease-activated receptor 2 prevents gingival inflammation and bone loss in a mouse model of periodontal disease.

Chronic periodontitis is characterised by gingival inflammation and alveolar bone loss. A major aetiological agent is Porphyromonas gingivalis, which secretes proteases that activate protease-activated receptor 2 (PAR2 ). PAR2 expressed on oral keratinocytes is activated by proteases released by P. gingivalis, inducing secretion of interleukin 6 (IL-6), and global knockout of PAR2 prevents bone loss and inflammation in a periodontal disease model in mice. To test the hypothesis that PAR2 expressed on gingival keratinocytes is required for periodontal disease pathology, keratinocyte-specific PAR2 -null mice were generated using K14-Cre targeted deletion of the PAR2 gene (F2rl1). These mice were subjected to a model of periodontitis involving placement of a ligature around a tooth, combined with P. gingivalis infection ("Lig + Inf"). The intervention caused a significant 44% decrease in alveolar bone volume (assessed by microcomputed tomography) in wildtype (K14-Cre:F2rl1wt/wt ), but not littermate keratinocyte-specific PAR2 -null (K14-Cre:F2rl1fl/fl ) mice. Keratinocyte-specific ablation of PAR2 prevented the significant Lig + Inf-induced increase (2.8-fold) in the number of osteoclasts in alveolar bone and the significant up-regulation (2.4-4-fold) of the inflammatory markers IL-6, IL-1ß, interferon-γ, myeloperoxidase, and CD11b in gingival tissue. These data suggest that PAR2 expressed on oral epithelial cells is a critical regulator of periodontitis-induced bone loss and will help in designing novel therapies with which to treat the disease.

ANALYSIS OF LOCAL IMMUNITY INDICATORS OF THE ORAL CAVITY AND DEGREE OF GINGIVITIS DEPENDING ON MUTATION OF CFTR GENE IN CHILDREN WITH CYSTIC FIBROSIS.

The aim of the work was to establish the relationship between the genotype of the cystic fibrosis transmembrane conductance regulator (CFTR), the level of local immune reactivity and the degree of chronic gingivitis in children with cystic fibrosis. The study has shown significant differences in the local immunity indices of the oral mucosa and the condition of periodontal tissues in children with cystic fibrosis in comparison with the control group. The features of the course of dental pathology among sick children, depending on the type of CFTR gene mutation are determined. Disturbance of mucosal immunity of the oral cavity in children with cystic fibrosis is manifested by a decrease in lysozyme activity in mixed saliva by 1.5 times and level of secretory immunoglobulins IgA by 1.4 times. A consequence of this is an increase of the degree of dysbiosis of the oral cavity by 3.7 times. At the same time, a lesser imbalance in the microflora and lysozyme activity observed in the homozygote group of the F508del mutation, and heterozygotes of the F508del mutation have the most severe manifestations of chronic gingivitis.

Structural insights unravel the zymogenic mechanism of the virulence factor gingipain K from Porphyromonas gingivalis, a causative agent of gum disease from the human oral microbiome.

Skewing of the human oral microbiome causes dysbiosis and preponderance of bacteria such as Porphyromonas gingivalis, the main etiological agent of periodontitis. P. gingivalis secretes proteolytic gingipains (Kgp and RgpA/B) as zymogens inhibited by a pro-domain that is removed during extracellular activation. Unraveling the molecular mechanism of Kgp zymogenicity is essential to design inhibitors blocking its activity. Here, we found that the isolated 209-residue Kgp pro-domain is a boomerang-shaped all-ß protein similar to the RgpB pro-domain. Using composite structural information of Kgp and RgpB, we derived a plausible homology model and mechanism of Kgp-regulating zymogenicity. Accordingly, the pro-domain would laterally attach to the catalytic moiety in Kgp and block the active site through an exposed inhibitory loop. This loop features a lysine (Lys129) likely occupying the S1 specificity pocket and exerting latency. Lys129 mutation to glutamate or arginine led to misfolded protein that was degraded in vivo Mutation to alanine gave milder effects but still strongly diminished proteolytic activity, without affecting the subcellular location of the enzyme. Accordingly, the interactions of Lys129 within the S1 pocket are also essential for correct folding. Uniquely for gingipains, the isolated Kgp pro-domain dimerized through an interface, which partially overlapped with that between the catalytic moiety and the pro-domain within the zymogen, i.e. both complexes are mutually exclusive. Thus, pro-domain dimerization, together with partial rearrangement of the active site upon activation, explains the lack of inhibition of the pro-domain in trans. Our results reveal that the specific latency mechanism of Kgp differs from those of Rgps.

Vitamin D Receptor TaqI Gene Polymorphism and Dental Caries in Czech Children.

AIM: We analyzed the VDR TaqI (rs731236) gene polymorphism in children with and those without dental caries. METHODS: A total of 388 subjects, 153 caries-free (with decayed/missing/filled teeth [DMFT] = 0) and 235 children with dental caries (DMFT ≥1), were genotyped by the TaqMan method. RESULTS: Although no significant differences in VDR TaqI allele and genotype frequencies between caries-free and caries-affected children were detected, a significant association between this polymorphism and gingivitis was found (p < 0.05). CONCLUSIONS: In contrast to previous studies from China and Turkey, the VDR TaqI gene variant cannot be used as a marker for identification of Czech children with increased dental caries risk.

Prevalence of Periodontal Destruction and Putative Periodontal Pathogens in the Same Lebanese Family.

AIM: Periodontal diseases are associated with microorganisms rich in Gram-negative species. Several studies have indicated the presence of few a periodontopathic microorganisms in the same family. A parent with severe adult periodontitis, who is infected with bacteria associated with periodontal disease, may function as a source of infection. Their children may be at a greater risk to become colonized with bacteria. The purpose of this investigation was (1) to explore the presence of three bacteria, such as Porphyromonas gingivalis (PG), Prevotella intermedia (PI), and Aggregatibacter actinomycetemcomitans (AA) in the same Lebanese family and (2) to study the clinical destruction in the same family and their relations as members of this family due to the presence of PG. MATERIALS AND METHODS: A total of 10 families were screened; only 5 (13 females and 5 males) were selected for this study, and at least one member of the family had untreated periodontal disease, chronic or aggressive. Every participant signed an informed consent form. A total of 18 available deoxyribonucleic acid (DNA) samples were taken to analyze the presence of three periodontal bacteria. STATISTICS: Multiple logistic regression was used for the exact methods. RESULTS: All 18 patients showed a positive result for PI. Also, PG. was recognized in 15 patients while AA was not detected in any of the subjects. All couples suffered from periodontitis, chronic or aggressive forms, five children suffered from gingivitis, three children had no clinical manifestation, and only one suffered from localized aggressive periodontitis. The statistical analysis showed with each 1 year of increase in age, the odds of having periodontal disease multiply by 1.39, i.e., age as a risk factor for periodontal disease due to the presence of PG and sharing the same plate. CONCLUSION: This investigation demonstrates a high prevalence of periodontal microorganisms in children and young adults of Lebanese periodontitis parents and a microbiological similarity between the children and their mothers. All these factors could be a high risk of developing periodontal disease in the future. CLINICAL SIGNIFICANCE: This article shows that vertical transmission of microorganisms is a possible risk factor for developing periodontal disease in the offspring.

LuxS signaling in Porphyromonas gingivalis-host interactions.

Dental plaque is a multispecies biofilm in the oral cavity that significantly influences oral health. The presence of the oral anaerobic pathogen Porphyromonas gingivalis is an important determinant in the development of periodontitis. Direct and indirect interactions between P. gingivalis and the host play a major role in disease development. Transcriptome analysis recently revealed that P. gingivalis gene-expression is regulated by LuxS in both an AI-2-dependent and an AI-2 independent manner. However, little is known about the role of LuxS-signaling in P. gingivalis-host interactions. Here, we investigated the effect of a luxS mutation on the ability of P. gingivalis to induce an inflammatory response in human oral cells in vitro. Primary periodontal ligament (PDL) fibroblasts were challenged with P. gingivalis ΔluxS or the wild-type parental strain and gene-expression of pro-inflammatory mediators IL-1ß, IL-6 and MCP-1 was determined by real-time PCR. The ability of P. gingivalis ΔluxS to induce an inflammatory response was severely impaired in PDL-fibroblasts. This phenotype could be restored by providing of LuxS in trans, but not by addition of the AI-2 precursor DPD. A similar phenomenon was observed in a previous transcriptome study showing that expression of PGN_0482 was reduced in the luxS mutant independently of AI-2. We therefore also analyzed the effect of a mutation in PGN_0482, which encodes an immuno-reactive, putative outer-membrane protein. Similar to P. gingivalis ΔluxS, the P. gingivalis Δ0482 mutant had an impaired ability to induce an inflammatory response in PDL fibroblasts. LuxS thus appears to influence the pro-inflammatory responses of host cells to P. gingivalis, likely through regulation of PGN_0482.

Can periodontal infection induce genotoxic effects?

OBJECTIVE: This study aimed to evaluate the occurrence of chromosomal abnormalities, through micronuclei, and apoptosis by the sum of karyorrhexis, pyknosis and condensed chromatin in individuals with chronic periodontitis, gingivitis associated with biofilm and no periodontal disease. MATERIALS AND METHODS: This study included 72 individuals divided into three groups: gingivitis (n = 21), periodontitis (n = 24) and control (n = 27). Information on sociodemographic characteristics, health and lifestyle was obtained. Full mouth clinical examination was performed to define the periodontal condition. Exfoliated cells from gingival mucosa were collected for computation of micronuclei and nuclear changes indicative of apoptosis. The differences in the occurrence of endpoints (micronucleus, karyorrhexis, pyknosis and condensed chromatin) were evaluated using the conditional test to compare proportions in a rare events situation. RESULTS: There was no statistically significant difference in the occurrence of micronucleus (p > 0.1) between gingivitis, periodontitis and control groups. The occurrence of apoptosis was significantly higher among individuals with periodontitis compared to individuals with gingivitis (p < 0.05) and controls (p < 0.025). CONCLUSIONS: The findings showed that the inflammatory process generated by gingivitis and periodontitis is not related to a higher occurrence of chromosomal damage. However, the higher occurrence of apoptosis in individuals with periodontitis points to genotoxic effects induced by periodontal infection.

Hereditary hyperplastic gingivitis in North American farmed silver fox (Vulpes vulpes).

Hereditary hyperplastic gingivitis is a progressive growth of gingival tissues in foxes resulting in dental encapsulation. It is an autosomal recessive condition displaying a gender-biased penetrance, with an association with superior fur quality. This disease has been primarily described in European farmed foxes. Here we document its emergence in Canada.

Gingivite hyperplasique héréditaire chez le renard argenté d'élevage d'Amérique du Nord(Vulpes vulpes). La gingivite hyperplasique héréditaire est une croissance progressive des tissus gingivaux chez les renards qui produit une encapsulation dentaire. Il s'agit d'une affection récessive autosomique qui manifeste une pénétration privilégiant un sexe et qui présente une association avec une qualité de fourrure supérieure. Cette maladie a été principalement décrite chez les renards d'élevage européen. Nous documentons ici son émergence au Canada.(Traduit par Isabelle Vallières).

Protective role for TLR4 signaling in atherosclerosis progression as revealed by infection with a common oral pathogen.

Clinical and epidemiological studies have implicated chronic infections in the development of atherosclerosis. It has been proposed that common mechanisms of signaling via TLRs link stimulation by multiple pathogens to atherosclerosis. However, how pathogen-specific stimulation of TLR4 contributes to atherosclerosis progression remains poorly understood. In this study, atherosclerosis-prone apolipoprotein-E null (ApoE(-/-)) and TLR4-deficient (ApoE(-/-)TLR4(-/-)) mice were orally infected with the periodontal pathogen Porphyromonas gingivalis. ApoE(-/-)TLR4(-/-) mice were markedly more susceptible to atherosclerosis after oral infection with P. gingivalis. Using live animal imaging, we demonstrate that enhanced lesion progression occurs progressively and was increasingly evident with advancing age. Immunohistochemical analysis of lesions from ApoE(-/-)TLR4(-/-) mice revealed an increased inflammatory cell infiltrate composed primarily of macrophages and IL-17 effector T cells (Th17), a subset linked with chronic inflammation. Furthermore, enhanced atherosclerosis in TLR4-deficient mice was associated with impaired development of Th1 immunity and regulatory T cell infiltration. In vitro studies suggest that the mechanism of TLR4-mediated protective immunity may be orchestrated by dendritic cell IL-12 and IL-10, which are prototypic Th1 and regulatory T cell polarizing cytokines. We demonstrate an atheroprotective role for TLR4 in response to infection with the oral pathogen P. gingivalis. Our results point to a role for pathogen-specific TLR signaling in chronic inflammation and atherosclerosis.

Association of pocket epithelial cell proliferation in periodontitis with TLR9 expression and inflammatory response.

BACKGROUND/PURPOSE: Inflammatory response is triggered after recognition of microbial ligands by innate receptors such as Toll-like receptors (TLRs) and Nucleotide oligomerization domain (NOD)-like receptors (NLRs). In this study, we examined serial frozen sections of gingival biopsies from patients with gingivitis or periodontitis by immunohistochemical analysis for the topographic expression patterns of selected innate receptors and their association with cell proliferation in clinically healthy and diseased gingival tissues. METHODS: A total of 19 gingival biopsies were collected from patients at the School of Dentistry, National Taiwan University Medical Center according to approved protocol and with informed consent. The specimens were assigned to either the gingivitis group or periodontitis group after clinical evaluation using gingival index. Frozen sections of gingival biopsies were stained with hematoxylin and eosin for histological evaluation. Serial sections of the same samples were stained with a panel of antibodies for immunohistochemical analysis. Expression of each protein marker was compared in the oral versus the sulcular epithelium of the same section. RESULTS: Expression of cytokeratin 19 (CK19) was markedly increased in the basement membranes of the oral epithelium and in all layers of the pocket epithelium where it caused evident cell proliferation and migration of sulcular epithelial cells into the lamina propria of periodontitis tissue. TLR4 and the cytoplasmic NLRP3 were expressed in all sections examined regardless of disease state. However, expression of TLR9-, CK19- and collagenolytic matrix metalloproteinase-13 and activated NF-κB subunit p65 was more commonly found in periodontitis tissues than in gingivitis tissues. CONCLUSION: Activation of TLR9 signaling in the pocket epithelium was highly associated with periodontal inflammation and possibly with loss of tissue integrity. Further studies of mechanisms by which TLR9 signaling is activated in the periodontal epithelium may lead to new strategies for treating periodontitis.