Interferon activated gene 204 protects against bone loss in experimental periodontitis.

BACKGROUND: Periodontal destruction can be the result of different known and yet-to-be-discovered biological pathways. Recent human genetic association studies have implicated interferon-gamma inducible protein 16 (IFI16) and absent in melanoma 2 (AIM2) with high periodontal interleukin (IL)-1ß levels and more destructive disease, but mechanistic evidence is lacking. Here, we sought to experimentally validate these observational associations and better understand IFI16 and AIM2's roles in periodontitis. METHODS: Periodontitis was induced in Ifi204-/- (IFI16 murine homolog) and Aim2-/- mice using the ligature model. Chimeric mice were created to identify the main source cells of Ifi204 in the periodontium. IFI16-silenced human endothelial cells were treated with periodontal pathogens in vitro. Periodontal tissues from Ifi204-/- mice were evaluated for alveolar bone (micro-CT), cell inflammatory infiltration (MPO+ staining), Il1b (qRT-PCR), and osteoclast numbers (cathepsin K+ staining). RESULTS: Ifi204-deficient mice> exhibited >20% higher alveolar bone loss than wild-type (WT) (P < 0.05), while no significant difference was found in Aim2-/- mice. Ifi204's effect on bone loss was primarily mediated by a nonbone marrow source and was independent of Aim2. Ifi204-deficient mice had greater neutrophil/macrophage trafficking into gingival tissues regardless of periodontitis development compared to WT. In human endothelial cells, IFI16 decreased the chemokine response to periodontal pathogens. In murine periodontitis, Ifi204 depletion elevated gingival Il1b and increased osteoclast numbers at diseased sites (P < 0.05). CONCLUSIONS: These findings support IFI16's role as a novel regulator of inflammatory cell trafficking to the periodontium that protects against bone loss and offers potential targets for the development of new periodontal disease biomarkers and therapeutics.

The prospective association between periodontal disease and brain imaging outcomes: The Atherosclerosis Risk in Communities study.

AIM: We investigate if periodontal disease is prospectively associated with cerebrovascular and neurodegenerative markers of dementia and Alzheimer's pathology. MATERIALS AND METHODS: N = 1306 participants (Visit 5 mean age = 76.5 [standard deviation = 5.4] years) in the Atherosclerosis Risk in Communities study with completed dental exams at Visit 4 underwent brain magnetic resonance imaging scans at Visit 5 while N = 248 underwent positron emission tomography scans. Participants were classified as edentulous or, among the dentate, by the modified Periodontal Profile Class. Brain volumes were regressed on periodontal status in linear regressions. Cerebrovascular measures and ß-amyloid positivity were regressed on periodontal status in logistic regressions. RESULTS: Periodontal disease was not associated with brain volumes, microhaemorrhages, or elevated ß-amyloid. Compared with periodontally healthy individuals, odds ratios [95% confidence interval] for all-type infarcts were 0.37 [0.20, 0.65] for severe tooth loss and 0.56 [0.31, 0.99] for edentulous participants. CONCLUSIONS: Within the limitations of this study, periodontal disease was not associated with altered brain volumes, microhaemorrhages, or ß-amyloid positivity. Tooth loss was associated with lower odds of cerebral infarcts.

Periodontal disease and incident dementia: The Atherosclerosis Risk in Communities Study (ARIC).

OBJECTIVE: To test the hypothesis that periodontal disease would be associated with increased risk for dementia and mild cognitive impairment (MCI) by assessing dementia/MCI outcomes after a baseline periodontal examination. METHODS: Participants enrolled in the Atherosclerosis Risk in Communities study with a clinical periodontal examination (or edentulous participants) at visit 4 (1996-1998; mean ± SD age 63 ± 6 years, 55% female, 21% black) and adjudicated dementia outcomes through 2016 were included (n = 8,275). A subgroup of 4,559 participants had adjudicated dementia and MCI assessments at visit 5 (2011-2013). Participants received a full-mouth periodontal examination and were classified into periodontal profile classes (PPCs) based on the severity and extent of gingival inflammation and attachment loss. MCI and dementia were determined via neurocognitive testing, neurological examination and history, informant interviews, and brain MRI in a subset. Cox proportional hazards models regressed incident dementia on PPCs. Relative risk regression models were used for the composite of MCI/dementia. RESULTS: The cumulative incidence and incidence density of dementia during follow-up (average 18.4 years) were 19% (n = 1,569) and 11.8 cases per 1,000 person-years. Multivariable adjusted hazard ratios for incident dementia among participants with severe PPC or edentulism (vs periodontal healthy) were 1.22 (95% confidence interval [CI] 1.01-1.47) and 1.21 (95% CI 0.99-1.48), respectively. For the combined dementia/MCI outcome, adjusted risk ratios among participants with mild/intermediate PPC, severe PPC, or edentulism (vs periodontal healthy) were 1.22 (95% CI 1.00-1.48), 1.15 (95% CI 0.88-1.51), and 1.90 (95% CI 1.40-2.58). Results were stronger among younger (≤62 years) participants (p for interaction = 0.02). CONCLUSION: Periodontal disease was modestly associated with incident MCI and dementia in a community-based cohort of black and white participants.

Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics.

Inflammasomes are a group of multimolecular intracellular complexes assembled around several innate immune proteins. Recognition of a diverse range of microbial, stress and damage signals by inflammasomes results in direct activation of caspase-1, which subsequently induces the only known form of secretion of active interleukin-1ß and interleukin-18. Although the importance of interleukin-1ß in the periodontium is not questioned, the impact of inflammasomes in periodontal disease and its potential for therapeutics in periodontology is still in its very early stages. Increasing evidence in preclinical models and human data strongly implicate the involvement of inflammasomes in a number of inflammatory, autoinflammatory and autoimmune disorders. Here we review: (a) the currently known inflammasome functions, (b) clinical/preclinical data supporting inflammasome involvement in the context of periodontal and comorbid diseases and (c) potential therapies targeting inflammasomes. To clarify further the inflammasome involvement in periodontitis, we present analyses of data from a large clinical study (n = 5809) that measured the gingival crevicular fluid-interleukin-1ß and grouped the participants based on current periodontal disease classifications. We review data on 4910 European-Americans that correlate 16 polymorphisms in the interleukin-1B region with high gingival crevicular fluid-interleukin-1ß levels. We show that inflammasome components are increased in diseased periodontal tissues and that the caspase-1 inhibitor, VX-765, inhibits ~50% of alveolar bone loss in experimental periodontitis. The literature review further supports that although patients clinically present with the same phenotype, the disease that develops probably has different underlying biological pathways. The current data indicate that inflammasomes have a role in periodontal disease pathogenesis. Understanding the contribution of different inflammasomes to disease development and distinct patient susceptibility will probably translate into improved, personalized therapies.

Social stratification, oral hygiene, and trajectories of dental caries among old Americans.

OBJECTIVE: This study analyzed how oral hygiene (i.e., brushing, rinsing, and flossing) influences the trajectories of dental caries (i.e., numbers of decayed, missing, and filled teeth) among older Americans within the context of social stratification. METHOD: Data came from Piedmont Dental Study that involved a sample of 810 older Americans who were dentate in 1988 with up to four repeated observations through 1994. Hierarchical linear models were used for data analysis. RESULTS: Brushing, flossing, and rinsing were associated with the trajectories of dental caries in distinct ways. In addition, oral hygiene was correlated with race, education, household income, and use of dental care. The effects of brushing and flossing on decayed and missing teeth remained robust, even when socio-demographic and health attributes were controlled. Conversely, socioeconomic disparities in dental caries persisted, when oral hygiene was adjusted. DISCUSSION: Both social stratification and oral hygiene need to be considered in promoting oral health.

Vitamin D status and periodontal disease among pregnant women.

BACKGROUND: Maternal periodontal disease is found in < or = 40% of pregnant women and is associated with adverse pregnancy outcomes. Vitamin D deficiency may play a role in periodontal disease and tooth loss, and insufficient vitamin D status is common among pregnant women. The objective of this study is to examine the relationship between maternal vitamin D status and periodontal disease. METHODS: A case-control study was conducted. Cases were defined as pregnant women with clinical moderate to severe periodontal disease; controls were pregnant women who were periodontally healthy. Maternal data were chart abstracted and serum was collected between 14 and 26 weeks of gestation. Serum 25-hydroxyvitamin D (25[OH]D) levels were measured using liquid chromatography-tandem mass spectrometry. Median serum 25(OH)D levels and prevalence of vitamin D insufficiency (defined as <75 nmol/l) were compared between cases and controls. The odds ratio and 95% confidence interval for moderate to severe periodontal disease among women with vitamin D insufficiency was calculated using multivariable logistic regression, adjusting for maternal race, season of blood draw, and other potential confounders. RESULTS: A total of 117 cases were compared to 118 controls. Cases had lower median 25(OH)D levels than controls (59 versus 100 nmol/l; P <0.001) and were more likely to have vitamin D insufficiency (65% versus 29%; P <0.001). The adjusted odds ratio (95% confidence interval) for moderate to severe periodontal disease among women with vitamin D insufficiency was 2.1 (0.99 to 4.5). CONCLUSIONS: Vitamin D insufficiency (serum 25[OH]D <75 nmol/l) is associated with maternal periodontal disease during pregnancy. Vitamin D supplementation represents a potential therapeutic strategy to improve maternal oral health.