Periodontitis is a highly prevalent, biofilm-mediated chronic inflammatory disease that results in the loss of the tooth-supporting tissues. It features two major clinical entities: chronic periodontitis, which is more common, and aggressive periodontitis, which usually has an early onset and a rapid progression. Natural killer (NK) cells are a distinct subgroup of lymphocytes that play a major role in the ability of the innate immune system to steer immune responses. NK cells are abundant in periodontitis lesions, and NK cell activation has been causally linked to periodontal tissue destruction. However, the exact mechanisms of their activation and their role in the pathophysiology of periodontitis are elusive. Here, we show that the predominant NK cell-activating molecule in periodontitis is CD2-like receptor activating cytotoxic cells (CRACC). We show that CRACC induction was significantly more pronounced in aggressive than chronic periodontitis and correlated positively with periodontal disease severity, subgingival levels of specific periodontal pathogens, and NK cell activation in vivo. We delineate how Aggregatibacter actinomycetemcomitans, an oral pathogen that is causally associated with aggressive periodontitis, indirectly induces CRACC on NK cells via activation of dendritic cells and subsequent interleukin 12 (IL-12) signaling. In contrast, we demonstrate that fimbriae from Porphyromonas gingivalis, a principal pathogen in chronic periodontitis, actively attenuate CRACC induction on NK cells. Our data suggest an involvement of CRACC-mediated NK cell activation in periodontal tissue destruction and point to a plausible distinction in the pathobiology of aggressive and chronic periodontitis that may help explain the accelerated tissue destruction in aggressive periodontitis.
We investigated the sequential gene expression in the gingiva during the induction and resolution of experimental gingivitis.
Twenty periodontally and systemically healthy non-smoking volunteers participated in a 3-week experimental gingivitis protocol, followed by debridement and 2-week regular plaque control. We recorded clinical indices and harvested gingival tissue samples from 4 interproximal palatal sites in half of the participants at baseline, Day 7, 14 and 21 (‘induction phase’), and at day 21, 25, 30 and 35 in the other half (‘resolution phase’). RNA was extracted, amplified, reversed transcribed, amplified, labeled and hybridized with Affymetrix Human Genome U133Plus2.0 microarrays. Paired t-tests compared gene expression changes between consecutive time points. Gene ontology analyses summarized the expression patterns into biologically relevant categories.
The median gingival index was 0 at baseline, 2 at Day 21 and 1 at Day 35. Differential gene regulation peaked during the third week of induction and the first four days of resolution. Leukocyte transmigration, cell adhesion and antigen processing/presentation were the top differentially regulated pathways.
Transcriptomic studies enhance our understanding of the pathobiology of the reversible inflammatory gingival lesion and provide a detailed account of the dynamic tissue responses during induction and resolution of experimental gingivitis.
Experimental gingivitis; microarray; gene expression; tissue response
To use linked electronic medical and dental records to discover associations between periodontitis and medical conditions independent of a priori hypotheses.
Materials and Methods
This case-control study included 2475 patients who underwent dental treatment at the College of Dental Medicine at Columbia University and medical treatment at NewYork-Presbyterian Hospital. Our cases are patients who received periodontal treatment and our controls are patients who received dental maintenance but no periodontal treatment. Chi-square analysis was performed for medical treatment codes and logistic regression was used to adjust for confounders.
Our method replicated several important periodontitis associations in a largely Hispanic population, including diabetes mellitus type I (OR = 1.6, 95% CI 1.30–1.99, p < 0.001) and type II (OR = 1.4, 95% CI 1.22–1.67, p < 0.001), hypertension (OR = 1.2, 95% CI 1.10–1.37, p < 0.001), hypercholesterolaemia (OR = 1.2, 95% CI 1.07–1.38, p = 0.004), hyperlipidaemia (OR = 1.2, 95% CI 1.06–1.43, p = 0.008) and conditions pertaining to pregnancy and childbirth (OR = 2.9, 95% CI: 1.32–7.21, p = 0.014). We also found a previously unreported association with benign prostatic hyperplasia (OR = 1.5, 95% CI 1.05–2.10, p = 0.026) after adjusting for age, gender, ethnicity, hypertension, diabetes, obesity, lipid and circulatory system conditions, alcohol and tobacco abuse.
This study contributes a high-throughput method for associating periodontitis with systemic diseases using linked electronic records.
data linkage; dental records; electronic health records; medical informatics; periodontal diseases
Previous studies report associations between periodontal infection and cardiorespiratory fitness but no study has examined the association among younger adults. Our objective was to study the association between clinical measures of periodontal infection and cardiorespiratory fitness levels among a population-based sample of younger adults.
The Continuous National Health and Nutrition Examination Survey 1999–2004 enrolled 2,863 participants (46% women) who received a partial-mouth periodontal examination and completed a submaximal treadmill test for the assessment of estimated VO2 max(eVO2 max ). Participants were mean±SD age 33±9 years (range = 20–49 years), 30% Hispanic, 48% White, 19% Black, and 3% other. Mean eVO2 max (mL/kg/minute) as well as eVO2 max≤32 mL/kg/minute (20th percentile) were regressed across quartiles of mean probing depth and mean attachment loss in multivariable linear and logistic regression models.
After multivariable adjustment, mean eVO2 max levels±SE across quartiles of attachment loss were 39.72±0.37, 39.64±0.34, 39.59±0.36, and 39.85±0.39 (P = 0.99). Mean eVO2 max±SE across quartiles of probing depth were 39.57±0.32, 39.78±0.38, 39.19±0.25, and 40.37±0.53 (P = 0.28). Similarly, multivariable adjusted mean eVO2 max values were similar between healthy participants vs. those with moderate/severe periodontitis: 39.70±0.21 vs. 39.70±0.90 (P = 1.00). The odds ratio (OR) for low eVO2 max comparing highest vs. lowest quartile of attachment loss = 0.89[95% CI 0.64–1.24]. The OR for comparing highest vs. lowest probing depth quartile = 0.77[95% CI 0.51–1.15].
Clinical measures of periodontal infection were not related to cardiorespiratory fitness in a sample of generally healthy younger adults.
Periodontitis is one of the most prevalent human inflammatory diseases. The major clinical phenotypes of this polymicrobial, biofilm-mediated disease are chronic and aggressive periodontitis, the latter being characterized by a rapid course of destruction that is generally attributed to an altered immune-inflammatory response against periodontal pathogens. Still, the biological basis for the pathophysiological distinction of the two disease categories has not been well documented yet.
Type I natural killer T (NKT) cells are a lymphocyte subset with important roles in regulating immune responses to either tolerance or immunity, including immune responses against bacterial pathogens. Here, we delineate the mechanisms of NKT cell activation in periodontal infections.
We show an infiltration of type I NKT cells in aggressive, but not chronic periodontitis lesions in vivo. Murine DCs infected with aggressive periodontitis-associated Aggregatibacter actinomycetemcomitans triggered a type I interferon response followed by type I NKT cell activation. In contrast, infection with Porphyromonas gingivalis, a principal pathogen in chronic periodontitis, did not induce NKT cell activation. This difference could be explained by the absence of a type I interferon response to P. gingivalis infection. We found these interferons to be critical for NKT cell activation.
Our study provides a conceivable biological distinction between the two periodontitis subforms and identifies factors required for the activation of the immune system in response to periodontal bacteria.
natural killer T cells; immune evasion; bacterial pathogenesis; Porphyromonas gingivalis; Aggregatibacter actinomycetemcomitans
We investigated the effect of comprehensive periodontal therapy on the levels of multiple systemic inflammatory biomarkers.
Thirty patients with severe periodontitis received comprehensive periodontal therapy within a 6-week period. Blood samples were obtained at: one week pre- therapy (T1), therapy initiation (T2), treatment completion (T3), and 4 weeks thereafter (T4). We assessed plasma concentrations of 19 biomarkers using multiplex assays, and serum IgG antibodies to periodontal bacteria using checkerboard immunoblotting. At T2 and T4, dental plaque samples were analyzed using checkerboard hybridizations.
At T3, PAI-1, sE-selectin, sVCAM-1, MMP-9, myeloperoxidase, and a composite Summary Inflammatory Score (SIS) were significantly reduced. However, only sE-selectin, sICAM, and serum amyloid P sustained a reduction at T4. Responses were highly variable: analyses of SIS slopes between baseline and T4 showed that approximately 1/3 and 1/4 of the patients experienced marked reduction and pronounced increase in systemic inflammation, respectively, while the remainder were seemingly unchanged. Changes in inflammatory markers correlated poorly with clinical, microbiological and serological markers of periodontitis.
Periodontal therapy resulted in an overall reduction of systemic inflammation, but the responses were inconsistent across subjects and largely not sustainable. The determinants of this substantial heterogeneity need to be explored further.
Periodontal therapy; inflammatory mediators; systemic inflammation; atherosclerotic vascular disease
Clinical and radiographic measures are gold standards for diagnosing periodontitis but offer little information regarding the pathogenesis of the disease. We hypothesized that a comparison of gene expression signatures between healthy and diseased gingival tissues would provide novel insights in the pathobiology of periodontitis, and would inform the design of future studies.
Ninety systemically healthy non-smokers with moderate to advanced periodontitis (63 with chronic and 27 with aggressive periodontitis) each contributed with ≥2 “diseased” interproximal papillae [with bleeding on probing (BoP), pocket depth (PD) ≥4mm, and attachment loss (AL) ≥3mm)] and a “healthy” papilla, if available (no BoP, PD ≤4mm and AL ≤2mm). RNA was extracted, amplified, reverse-transcribed, labeled, and hybridized with AffymetrixU133Plus2.0 arrays. Differential expression was assayed in 247 individual tissue samples (183 from diseased and 64 from healthy sites) using a standard mixed-effects linear model approach, with patient effects considered random with a normal distribution, and gingival tissue status considered a two-level fixed effect. Gene ontology analysis summarized the expression patterns into biologically relevant categories.
Transcriptome analysis revealed that a total of 12,744 probe sets were differentially expressed after adjusting for multiple comparisons (p<9.15×10-7). Of those, 5,295 were up-regulated and 7,449 down-regulated in disease when compared to health. Gene ontology analysis identified 61 differentially expressed groups (adjusted p<0.05) including apoptosis, antimicrobial humoral response, antigen presentation, regulation of metabolic processes, signal transduction, and angiogenesis.
Gingival tissue transcriptomes provide a valuable scientific tool for further hypothesis-driven studies of the pathobiology of periodontitis.
Periodontitis; genomics; infection; gene expression; microarray
We investigated the effects of periodontal therapy on gene expression of peripheral blood monocytes.
Fifteen patients with periodontitis gave blood samples at four time points: 1 week before periodontal treatment (#1), at treatment initiation (baseline, #2), 6-week (#3) and 10-week post-baseline (#4). At baseline and 10 weeks, periodontal status was recorded and subgingival plaque samples were obtained. Periodontal therapy (periodontal surgery and extractions without adjunctive antibiotics) was completed within 6 weeks. At each time point, serum concentrations of 19 biomarkers were determined. Peripheral blood monocytes were purified, RNA was extracted, reverse-transcribed, labelled and hybridized with AffymetrixU133Plus2.0 chips. Expression profiles were analysed using linear random-effects models. Further analysis of gene ontology terms summarized the expression patterns into biologically relevant categories. Differential expression of selected genes was confirmed by real-time reverse transcriptase-polymerase chain reaction in a subset of patients.
Treatment resulted in a substantial improvement in clinical periodontal status and reduction in the levels of several periodontal pathogens. Expression profiling over time revealed more than 11,000 probe sets differentially expressed at a false discovery rate of <0.05. Approximately 1/3 of the patients showed substantial changes in expression in genes relevant to innate immunity, apoptosis and cell signalling.
The data suggest that periodontal therapy may alter monocytic gene expression in a manner consistent with a systemic anti-inflammatory effect.
atherosclerosis; cytokines; genomics; infection; inflammation; periodontitis
To compare the prevalence of periodontal disease between two randomly selected population-based studies (the Oral Infections and Vascular Disease Epidemiology Study (INVEST) and the Study of Health in Pomerania (SHIP)) and address relevant methodological issues.
Comparison was restricted to 55–81-years-olds. Attachment loss (AL), probing depth (PD), and tooth count were assessed in INVEST (full-mouth, six sites) and SHIP (half-mouth, four sites). Subjects were classified according to the CDC/AAP case definition. Recording protocols were standardized. Mixed linear or logistic models were used to compare INVEST with SHIP.
Mean half-mouth AL was lower in INVEST vs. SHIP (INVEST: 2.9mm versus SHIP: 4.0mm, p<0.05). Findings were similar across multiple periodontal disease definitions. After equalisation of recording protocols and adjustment for periodontal risk factors, mean AL and PD were 1.2mm and 0.3mm lower in INVEST vs. SHIP (p<0.001). The odds for severe periodontitis (CDC/AAP) was 0.2-fold in INVEST vs. SHIP (p<0.001). Confounding effects of age, gender, race/ethnicity, education, and use of interdental care devices were highest as indicated by change-in-estimate for study.
Implementation of the proposed method for comparison of epidemiological studies revealed that periodontitis was less prevalent in INVEST compared to SHIP, even after extensive risk-factor adjustment.
Cross-cultural comparison; Periodontal disease; Attachment loss; Probing depth; Periodontal risk factors
No prospective studies exist on the relationship between change in periodontal clinical and microbiological status and progression of carotid atherosclerosis.
Methods and Results
The Oral Infections and Vascular Disease Epidemiology Study examined 420 participants at baseline (68±8 years old) and follow‐up. Over a 3‐year median follow‐up time, clinical probing depth (PD) measurements were made at 75 766 periodontal sites, and 5008 subgingival samples were collected from dentate participants (average of 7 samples/subject per visit over 2 visits) and quantitatively assessed for 11 known periodontal bacterial species by DNA‐DNA checkerboard hybridization. Common carotid artery intima‐medial thickness (CCA‐IMT) was measured using high‐resolution ultrasound. In 2 separate analyses, change in periodontal status (follow‐up to baseline), defined as (1) longitudinal change in the extent of sites with a ≥3‐mm probing depth (Δ%PD≥3) and (2) longitudinal change in the relative predominance of bacteria causative of periodontal disease over other bacteria in the subgingival plaque (Δetiologic dominance), was regressed on longitudinal CCA‐IMT progression adjusting for age, sex, race/ethnicity, diabetes, smoking status, education, body mass index, systolic blood pressure, and low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol. Mean (SE) CCA‐IMT increased during follow‐up by 0.139±0.008 mm. Longitudinal IMT progression attenuated with improvement in clinical or microbial periodontal status. Mean CCA‐IMT progression varied inversely across quartiles of longitudinal improvement in clinical periodontal status (Δ%PD≥3) by 0.18 (0.02), 0.16 (0.01), 0.14 (0.01), and 0.07 (0.01) mm (P for trend<0.0001). Likewise, mean CCA‐IMT increased by 0.20 (0.02), 0.18 (0.02), 0.15 (0.02), and 0.12 (0.02) mm (P<0.0001) across quartiles of longitudinal improvement in periodontal microbial status (Δetiologic dominance).
Longitudinal improvement in clinical and microbial periodontal status is related to a decreased rate of carotid artery IMT progression at 3‐year average follow‐up.
atherosclerosis; infection; inflammation; periodontal; progression
Adverse microbial exposures might contribute to diabetogenesis. We hypothesized that clinical periodontal disease (a manifestation of microbial exposures in dysbiotic biofilms) would be related to insulin resistance among diabetes-free participants. The roles of inflammatory mediation and effect modification were also studied.
RESEARCH DESIGN AND METHODS
The continuous National Health and Nutrition Examination Survey 1999–2004 enrolled 3,616 participants (51% women) who received a periodontal examination and fasting blood draw. Participants were mean age (± SD) 43 ± 17 years and 28% Hispanic, 52% Caucasian, 17% African American, and 3% other. Log-transformed values of the homeostasis model assessment of insulin resistance (HOMA-IR) or HOMA-IR ≥3.30 (75th percentile) were regressed across full-mouth periodontal probing depth (PD) levels using linear and logistic models. White blood cell (WBC) count and C-reactive protein (CRP) were considered as either mediators or effect modifiers in separate analyses. Risk ratios (RRs) stem from marginal predictions derived from the logistic model. Results were adjusted for multiple periodontal disease and insulin resistance risk factors.
In linear regression, geometric mean HOMA-IR levels increased by 1.04 for every 1-mm PD increase (P = 0.007). WBC mediated 6% of the association (P < 0.05). Among participants with WBC ≤6.4 × 109, PD was unrelated to HOMA-IR ≥3.30. Fourth-quartile PD was associated with HOMA-IR ≥3.30 among participants with WBC >7.9 × 109; RR 2.60 (1.36–4.97) (P for interaction = 0.05). Findings were similar among participants with CRP >3.0 mg/L (P for interaction = 0.04).
Periodontal infection was associated with insulin resistance in a nationally representative U.S. sample of diabetes-free adults. These data support the role of inflammation as both mediator and effect modifier of the association.
“Diabetes and Oral Disease: Implications for Health Professionals” was a one-day conference convened by the Columbia University College of Dental Medicine, the Columbia University College of Physicians and Surgeons, and the New York Academy of Sciences on May 4, 2011in New York City. The program included an examination of the bidirectional relationship between oral disease and diabetes and the inter-professional working relationships for the care of people who have diabetes. The overall goal of the conference was to promote discussion among the healthcare professions who treat people with diabetes, encourage improved communication and collaboration among them and ultimately, improve patient management of the oral and overall effects of diabetes. Attracting over 150 members of the medical and dental professions from eight different countries, the conference included speakers from academia and government and was divided into four sessions. This report summarizes the scientific presentations of the event.
diabetes; oral disease; meeting report
Chronic infections, including periodontal infections, may predispose to cardiovascular disease. We investigated the relationship between periodontal microbiota and hypertension. Methods and Results: 653 dentate men and women with no history of stroke or myocardial infarction were enrolled in INVEST. We collected 4533 subgingival plaque samples (average of 7 samples/subject). These were quantitatively assessed for 11 periodontal bacteria using DNA-DNA checkerboard hybridization. Cardiovascular risk factor measurements were obtained. Blood pressure and hypertension (systolic blood pressure≥140 mmHg, diastolic blood pressure≥90 mmHg or taking antihypertensive medication, or self-reported history) were each regressed on the level of bacteria: (1) considered causative of periodontal disease (etiologic bacterial burden); (2) associated with periodontal disease (putative bacterial burden); (3) associated with periodontal health (health associated bacterial burden). All analyses were adjusted for age, race/ethnicity, gender, education, body mass index, smoking, diabetes, LDL and HDL cholesterol. Etiologic bacterial burden was positively associated with both blood pressure and prevalent hypertension. Comparing the highest vs. lowest tertiles of etiologic bacterial burden, SBP was 9 mmHg higher, DBP was 5 mmHg higher (p for linear trend <0.001 in each case), and the odds ratio for prevalent hypertension was 3.05 (95%CI:1.60,5.82) after multivariable adjustment.
Our data provide evidence of a direct relationship between the levels of subgingival periodontal bacteria and both systolic and diastolic blood pressure as well as hypertension prevalence.
infection; inflammation; hypertension; blood pressure; epidemiology; periodontitis
Some maternal infections are associated with impaired infant cognitive and motor performance. Periodontitis results in frequent bacteremia and elevated serum inflammatory mediators.
The purpose of this study was to determine if periodontitis treatment in pregnant women affects infant cognitive, motor, or language development.
Children born to women who had participated in a previous trial were assessed between 24 and 28 months of age by using the Bayley Scales of Infant and Toddler Development (Third Edition) and the Preschool Language Scale (Fourth Edition). Information about the pregnancy, neonatal period, and home environment was obtained through chart abstractions, laboratory test results, and questionnaires. We compared infants born to women treated for periodontitis before 21 weeks' gestation (treatment group) or after delivery (controls). In unadjusted and adjusted analyses, associations between change in maternal periodontal condition during pregnancy and neurodevelopment scores were tested by using Student's t tests and linear regression.
A total of 411 of 791 eligible mother/caregiver-child pairs participated. Thirty-seven participating children (9.0%) were born at <37 weeks' gestation. Infants in the treatment and control groups did not differ significantly for adjusted mean cognitive (90.7 vs 91.4), motor (96.8 vs 97.2), or language (92.2 vs 92.1) scores (all P > .5). Results were similar in adjusted analyses. Children of women who experienced greater improvements in periodontal health had significantly higher motor and cognitive scores (P = .01 and .02, respectively), although the effect was small (∼1-point increase for each SD increase in the periodontal measure).
Nonsurgical periodontitis treatment in pregnant women was not associated with cognitive, motor, or language development in these study children.
child neurodevelopment; periodontitis; pregnancy; treatment
Determine if periodontitis progression during pregnancy is associated with adverse birth outcomes.
Materials and Methods
We used clinical data and birth outcomes from the OPT Study, which randomized women to receive periodontal treatment before 21 weeks gestation (N=413) or after delivery (410). Birth outcomes were available for 812 women and follow-up periodontal data for 722, including 75 whose pregnancies ended <37 weeks. Periodontitis progression was defined as ≥ 3mm loss of clinical attachment. Birth outcomes were compared between non-progressing and progressing groups using the log rank and t tests, separately in all women and in untreated controls.
The distribution of gestational age at the end of pregnancy (P > 0.1) and mean birthweight (3295 versus 3184 grams, P = 0.11) did not differ significantly between women with and without disease progression. Gestational age and birthweight were not associated with change from baseline in percent of tooth sites with bleeding on probing or between those who did versus did not progress according to a published definition of disease progression (P > 0.05).
In these women with periodontitis and within this study’s limitations, disease progression was not associated with increased risk for delivering a preterm or low birthweight infant.
Maternal periodontitis and disease progression during pregnancy have been associated with elevated risk for preterm birth. We used data from a recent clinical trial to explore possible associations between progressive periodontitis and birth outcomes.
The distribution of gestational age at delivery and mean birthweights did not differ significantly between women who experienced progressive periodontitis and those who did not.
While it is important to treat dental diseases, including periodontitis, during pregnancy, women whose periodontal condition worsens during pregnancy are not at elevated risk for adverse pregnancy outcomes.
preterm birth; low birthweight; periodontal disease; pregnancy; disease progression
Chronic infections, including periodontal infections, may predispose to cardiovascular disease. We investigated the relationship between periodontal microbiota and subclinical atherosclerosis.
Methods and Results
Of 1056 persons (age 69±9 years) with no history of stroke or myocardial infarction enrolled in the Oral Infections and Vascular Disease Epidemiology Study (INVEST), we analyzed 657 dentate subjects. Among these subjects, 4561 subgingival plaque samples were collected (average of 7 samples/subject) and quantitatively assessed for 11 known periodontal bacteria by DNA-DNA checkerboard hybridization. Extensive in-person cardiovascular risk factor measurements, a carotid scan with high-resolution B-mode ultrasound, white blood cell count, and C-reactive protein values were obtained. In 3 separate analyses, mean carotid artery intima-media thickness (IMT) was regressed on tertiles of (1) burden of all bacteria assessed, (2) burden of bacteria causative of periodontal disease (etiologic bacterial burden), and (3) the relative predominance of causative/over other bacteria in the subgingival plaque. All analyses were adjusted for age, race/ethnicity, gender, education, body mass index, smoking, diabetes, systolic blood pressure, and LDL and HDL cholesterol. Overall periodontal bacterial burden was related to carotid IMT. This relationship was specific to causative bacterial burden and the dominance of etiologic bacteria in the observed microbiological niche. Adjusted mean IMT values across tertiles of etiologic bacterial dominance were 0.84, 0.85, and 0.88 (P=0.002). Similarly, white blood cell values increased across tertiles of etiologic bacterial burden from 5.57 to 6.09 and 6.03 cells × 109/L (P=0.01). C-reactive protein values were unrelated to periodontal microbial status (P=0.82).
Our data provide evidence of a direct relationship between periodontal microbiology and subclinical atherosclerosis. This relationship exists independent of C-reactive protein.
infection; inflammation; atherosclerosis; epidemiology; carotid arteries
Epidemiologic studies of periodontal infection as a risk factor for cardiovascular disease often use clinical periodontal measures as a surrogate for the underlying bacterial exposure of interest. There are currently no methodological studies evaluating which clinical periodontal measures best reflect the levels of subgingival bacterial colonization in population-based settings. We investigated the characteristics of clinical periodontal definitions that were most representative of exposure to bacterial species that are believed to be either markers, or themselves etiologic, of periodontal disease.
706 men and women aged ≥ 55 years, residing in northern Manhattan were enrolled. Using DNA-DNA checkerboard hybridization in subgingival biofilms, standardized values for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia were averaged within mouth and summed to define "bacterial burden". Correlations of bacterial burden with clinical periodontal constructs defined by the severity and extent of attachment loss (AL), pocket depth (PD) and bleeding on probing (BOP) were assessed.
Clinical periodontal constructs demonstrating the highest correlations with bacterial burden were: i) percent of sites with BOP (r = 0.62); ii) percent of sites with PD ≥ 3 mm (r = 0.61); and iii) number of sites with BOP (r = 0.59). Increasing PD or AL severity thresholds consistently attenuated correlations, i.e., the correlation of bacterial burden with the percent of sites with PD ≥ 8 mm was only r = 0.16.
Clinical exposure definitions of periodontal disease should incorporate relatively shallow pockets to best reflect whole mouth exposure to bacterial burden.
Accumulating evidence has demonstrated an association between periodontal infectious agents, such as Porphyromonas gingivalis, and vascular disease. Tissue factor (TF) and its specific tissue factor pathway inhibitor (TFPI) are produced by vascular smooth cells and are important regulators of the coagulation cascade.
Materials and Methods
To assess the role of P. gingivalis in atherothrombosis, we infected primary human aortic smooth cells (HASMC) with either P. gingivalis 381, its non-invasive mutant DPG3, or heat-killed P. gingivalis 381. Levels and activity of TF and TFPI were measured 8 and 24 hours after infection in cell extracts and cell culture supernatants.
P. gingivalis 381 did not affect total TF antigen or TF activity in HASMC, but it significantly suppressed TFPI levels and activity compared to uninfected control cells, and those infected with the non-invasive mutant strain or the heat-killed bacteria. Further, P. gingivalis' LPS (up to a concentration of 5 μg/ml) failed to induce prothrombotic effects in HASMC, suggesting a significant role for the ability of whole viable bacteria to invade this cell type.
These data demonstrate for the first time that infection with a periodontal pathogen induces a prothrombotic response in HASMC.
infection; periodontitis; P. gingivalis; thrombosis; atherosclerosis; smooth muscle cell
Periodontitis is a chronic inflammatory disease caused by the microbiota of the periodontal pocket. We investigated the association between subgingival bacterial profiles and gene expression patterns in gingival tissues of patients with periodontitis. A total of 120 patients undergoing periodontal surgery contributed with a minimum of two interproximal gingival papillae (range 2-4) from a maxillary posterior region. Prior to tissue harvesting, subgingival plaque samples were collected from the mesial and distal aspects of each tissue sample. Gingival tissue RNA was extracted, reverse-transcribed, labeled, and hybridized with whole-genome microarrays (310 in total). Plaque samples were analyzed using checkerboard DNA-DNA hybridizations with respect to 11 bacterial species. Random effects linear regression models considered bacterial levels as exposure and expression profiles as outcome variables. Gene Ontology analyses summarized the expression patterns into biologically relevant categories.
Wide inter-species variation was noted in the number of differentially expressed gingival tissue genes according to subgingival bacterial levels: Using a Bonferroni correction (p < 9.15 × 10-7), 9,392 probe sets were differentially associated with levels of Tannerella forsythia, 8,537 with Porphyromonas gingivalis, 6,460 with Aggregatibacter actinomycetemcomitans, 506 with Eikenella corrodens and only 8 with Actinomyces naeslundii. Cluster analysis identified commonalities and differences among tissue gene expression patterns differentially regulated according to bacterial levels.
Our findings suggest that the microbial content of the periodontal pocket is a determinant of gene expression in the gingival tissues and provide new insights into the differential ability of periodontal species to elicit a local host response.
Background and Purpose
Chronic periodontitis (CP) is associated with stroke and subclinical atherosclerosis, but clinical measurement of CP can be time consuming and invasive. The purpose of this study was to determine whether radiographically assessed CP is associated with nonstenotic carotid artery plaque as an ultrasound measure of subclinical atherosclerosis.
Panoramic oral radiographs were obtained from 203 stroke-free subjects ages 54 to 94 during the baseline examination of the Oral Infections and Vascular Disease Epidemiology Study (INVEST). CP exposure among dentate subjects was defined either categorically (periodontal bone loss ≥50% [severe] versus <50% bone loss) or via tertile formation (for dose-response investigation), with edentulous subjects categorized separately. In all subjects, high-resolution B-mode carotid ultrasound was performed. Carotid plaque thickness (CPT) and prevalence (present/absent) were recorded. Covariates included age, sex, smoking, diabetes, hypertension, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol.
Among dentate subjects with severe periodontal bone loss, mean CPT was significantly greater (1.20±1.00 mm versus 0.73±0.89 mm; P=0.003). CPT increased with more severe bone loss (upper versus lower tertile bone loss; P=0.049; adjusted for age, sex, and hypertension). This apparent dose-response effect was more evident among never-smokers. In a fully adjusted multivariate logistic regression model, severe periodontal bone loss was associated with a nearly 4-fold increase in risk for the presence of carotid artery plaque (adjusted odds ratio, 3.64; CI, 1.37 to 9.65).
Severe periodontal bone loss is associated independently with carotid atherosclerosis. Panoramic oral radiographs may thus provide an efficient means to assess CP in studies of atherosclerosis risk.
alveolar bone loss; carotid stenosis; periodonitis; radiography; panoramic; ultrasonography
Background and Purpose
Chronic infections, including periodontal infections, may predispose to cardiovascular disease. The present study investigates the relationship of periodontal disease and tooth loss with subclinical atherosclerosis.
We enrolled 711 subjects with a mean age of 66±9 years and no history of stroke or myocardial infarction in the Oral Infections and Vascular Disease Epidemiology Study. Subjects received a comprehensive periodontal examination, extensive in-person cardiovascular disease risk factor measurements, and a carotid scan using high-resolution B-mode ultrasound. Regression models were adjusted for conventional risk factors (age, sex, smoking, diabetes, systolic blood pressure, low- and high-density lipoprotein cholesterol, race-ethnicity, education, physical activity) and markers of cultural background, healthy lifestyle, and psychosocial health.
Measures of both current and cumulative periodontitis became more severe as tooth loss increased. A significant association was observed between tooth loss levels and carotid artery plaque prevalence. Among those with 0 to 9 missing teeth, 46% had carotid artery plaque, whereas among those with ≥10 missing teeth, carotid artery plaque prevalence was ≈60% (P<0.05).
Our data suggest that tooth loss is a marker of past periodontal disease in this population and is related to subclinical atherosclerosis, thereby providing a potential pathway for a relationship with clinical events.
atherosclerosis; infection; periodontal disease; tooth loss