The objective of this study was to characterize the subgingival microbiota of African-American children with Localized Aggressive Periodontitis (LAP). Fifty-one children were included. Subgingival plaque samples were taken from diseased (DD) and healthy sites (DH) in LAP and from healthy sites in HS and HC and analyzed by 16S rRNA-based microarrays. Aggregatibacter actinomycetemcomitans (Aa) was the only species found to be both more prevalent (OR = 8.3, p = 0.0025) and abundant (p < 0.01) in DD. Filifactor alocis (Fa) was also found to be more prevalent in DD (OR 2.31, CI 1.06-5.01, p = 0.03). Most prevalent species in healthy sites were Selenomonas spp, Veillonella spp, Streptococcus spp, Bergeyella sp, and Kingella oralis. Overall, Streptococcus spp, Campylobacter gracilis, Capnocytophaga granulosa, Haemophilus parainfluenzae, and Lautropia mirabilis were most abundant in healthy children, while Aa, Fa, Tannerella sp, Solobacterium moorei, Parvimonas micra, and Capnocytophaga sp were most abundant in LAP. Based on a comprehensive analysis with 16S rRNA-based microarrays, Aa was strongly associated and site-specific in LAP. In contrast, other species were found to be associated with healthy sites and individuals (ClinicalTrials.gov number CT01330719).
Abbreviations: healthy site in healthy sibling (HS); healthy site in healthy control child (HC).
localized aggressive periodontitis; diagnosis; microbiology; Aggregatibacter actinomycetemcomitans; HOMIM; subgingival microbiota
To gain insights into the in vivo function of miRNAs in the context of periodontitis, we examined the occurrence of miRNAs in healthy and diseased gingival tissues and validated their in silico-predicted targets through mRNA profiling using whole-genome microarrays in the same specimens. Eighty-six individuals with periodontitis contributed 198 gingival papillae: 158 ‘diseased’ (bleeding-on-probing, PD > 4 mm, and AL ≥ 3 mm) and 40 ‘healthy’ (no bleeding, PD ≤ 4 mm, and AL ≤ 2 mm). Expression of 1,205 miRNAs was assessed by microarrays, followed by selected confirmation by quantitative RT-PCR. Predicted miRNA targets were identified and tested for enrichment by Gene Set Enrichment Analysis (GSEA). Enriched gene sets were grouped in functional categories by DAVID and Ingenuity Pathway Analysis. One hundred fifty-nine miRNAs were significantly differentially expressed between healthy and diseased gingiva. Four miRNAs (hsa-miR-451, hsa-miR-223, hsa-miR-486-5p, hsa-miR-3917) were significantly overexpressed, and 7 (hsa-miR-1246, hsa-miR-1260, hsa-miR-141, hsa-miR-1260b, hsa-miR-203, hsa-miR-210, hsa-miR-205*) were underexpressed by > 2-fold in diseased vs. healthy gingiva. GSEA and additional filtering identified 60 enriched miRNA gene sets with target genes involved in immune/inflammatory responses and tissue homeostasis. This is the first study that concurrently examined miRNA and mRNA expression in gingival tissues and will inform mechanistic experimentation to dissect the role of miRNAs in periodontal tissue homeostasis and pathology.
gene expression; transcriptome; periodontitis; pathogenesis; inflammation; human
Amelogenin, the major protein of forming dental enamel, plays a crucial role in the biomineralization of this tissue. Amelogenin is soluble at low pH and self-assembles to form higher order structures at physiological pH. To understand the mechanisms of its assembly and interactions with calcium phosphate mineral, we conducted FTIR spectroscopy (FTIRS) studies of pH-triggered assembly of recombinant porcine amelogenin rP172 and its interactions with mature hydroxyapatite and apatitic mineral formed in situ. Analysis of our data indicated that rP172 at pH 3.0 exists in an unfolded disordered state, while increases in pH led to structural ordering, manifested by increases in intra- and intermolecular β-sheet structures and a decrease in random coil and β-turns. Amelogenin assembled at pH 7.2 was also found to contain large portions of extended intramolecular β-sheet and PPII. These FTIRS findings are consistent with those previously obtained with other techniques, thus verifying the validity of our experimental approach. Interestingly, interactions with mineral led to a reduction in protein structural organization. The findings obtained show that amelogenin has intrinsic structural flexibility to accommodate interactions with both forming and mature calcium phosphate mineral phases, providing new insights into the potential importance of amelogenin-mineral interactions in enamel biomineralization.
enamel; hydroxyapatite; protein self-assembly; protein-mineral interactions; biomineralization; intrinsically disordered protein
Most studies linking obesity and periodontal disease have been cross-sectional in design. We examined whether gains in body weight, waist circumference, and arm fat area are associated with periodontitis progression in 893 non-diabetic men followed for up to four decades in the prospective VA Dental Longitudinal Study. Probing pocket depth (PPD) was measured by calibrated examiners. Repeated-measures generalized linear models estimated the mean cumulative numbers of teeth with PPD events (PPD > 3 mm) at each dental examination and the slopes associated with increasing numbers of affected teeth over time. Means were adjusted for baseline PPD, education, and cigarette pack-years, and time-dependent values of age, mean plaque score, cigarette packs/day, brushing, and flossing. Men who were overweight at baseline and gained weight most rapidly (> 0.19 kg/yr or ~15 lb during follow-up) had significantly more PPD events than men in the lowest tertile of weight gain (≤ -0.05 kg/yr). Overweight men whose waist circumference increased > 0.14–0.39 or > 0.39 cm/yr experienced more PPD events than men in the lowest tertile (≤ 0.14 cm/yr). Increase in arm fat area was associated with disease progression in normal-weight men. These results suggest that tracking adiposity changes with easily obtained anthropometric measures may help predict risk of periodontitis progression.
overweight; obesity; body mass index; waist circumference; adiposity; periodontal disease
Secondary caries remains the main problem limiting the longevity of composite restorations. The objective of this study was to investigate the remineralization of demineralized human enamel in vitro via a nanocomposite containing nanoparticles of amorphous calcium phosphate (NACP). NACP were synthesized by a spray-drying technique and incorporated into a dental resin. First, caries-like subsurface enamel lesions were created via an acidic solution. Then, NACP nanocomposite or a commercial fluoride-releasing control composite was placed on the demineralized enamel, along with control enamel without a composite. These specimens were then treated with a cyclic demineralization/remineralization regimen for 30 days. Quantitative microradiography showed typical enamel subsurface demineralization before cyclic demineralization/remineralization treatment, and significant remineralization in enamel under the NACP nanocomposite after the demineralization/remineralization treatment. The NACP nanocomposite had the highest enamel remineralization (mean ± SD; n = 6) of 21.8 ± 3.7%, significantly higher than the 5.7 ± 6.9% for fluoride-releasing composite (p < 0.05). The enamel group without composite had further demineralization of −26.1 ± 16.2%. In conclusion, a novel NACP nanocomposite was effective in remineralizing enamel lesions in vitro. Its enamel remineralization was 4-fold that of a fluoride-releasing composite control. Combined with the good mechanical and acid-neutralization properties reported earlier, the new NACP nanocomposite is promising for remineralization of demineralized tooth structures.
dental nanocomposite; calcium phosphate nanoparticles; human enamel; lesion remineralization; contact microradiography; caries inhibition
Dental pulp stem cells (DPSCs) possess immunoregulatory properties, but the underlying mechanism is not fully understood. Here we showed that DPSCs were capable of inducing activated T-cell apoptosis in vitro and ameliorating inflammatory-related tissue injuries when systemically infused into a murine colitis model. Mechanistically, DPSC-induced immunoregulation was associated with the expression of Fas ligand (FasL), a transmembrane protein that plays an important role in inducing the Fas apoptotic pathway. Knockdown of FasL expression by siRNA in DPSCs reduced their capacity to induce T-cell apoptosis in vitro and abolished their therapeutic effects in mice with colitis. However, the expression level of FasL did not affect either DPSC proliferation rate or multipotent differentiation potential. In summary, FasL governs the immunoregulatory property of DPSCs in the context of inducing T-cell apoptosis.
dental pulp stem cells; immunomodulation; Fas ligand; T-cells; apoptosis; differentiation
An extensive analysis of dental plaque samples over the years has led to the identification of “red” complex oral bacteria that have a strong association with each other and with disease. Consequently, these bacteria have been labeled ‘periopathogens’. Studies with one of these bacteria, Porphyromonas gingivalis, have revealed that it contains several different mechanisms which either impede or modulate periodontal protective mechanisms. In a mouse model of periodontitis, it has been shown that modulation of complement function by P. gingivalis facilitates a significant change in both the amount and composition of the normal oral microbiotia. This altered oral commensal microbiota is responsible for pathologic bone loss in the mouse. Thus, P. gingivalis creates a dysbiosis between the host and dental plaque, and this may represent one mechanism by which periodontitis can be initiated. We have therefore termed P. gingivalis a keystone pathogen.
bacteria; innate immunity; microbial ecology; microbiology; periodontal disease(s); periodontitis
This clinical trial tested the effect of daily application of 10% w/v calcium phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste for 1 yr when added to regular toothbrushing with fluoridated toothpaste to prevent dental caries in pre-school children. High-caries-risk children aged 2½ to 3½ yrs in a suburban area of central Thailand were assigned to receive either CPP-ACP (n = 150) or a placebo control (n = 146) in addition to fluoridated toothpaste. The International Caries Detection and Assessment System (ICDAS) was recorded at baseline, 6 mos, and 1 yr. At 1 yr, a significant increase in mean numbers of enamel and dentin caries lesions, as well as dmfs, was found in both groups (p < 0.001). No significant difference was observed between groups on these 3 outcome measures (p = 0.23, 0.84, and 0.91, respectively). The odds of enamel caries lesion transitions to a state of regression or stability, compared with progression from baseline, was also not different between groups [OR = 1.00, 95% CI (0.86, 1.17)]. This trial found that daily application of 10% w/v CPP-ACP paste on school days for 1 yr, when added to regular toothbrushing with a fluoride toothpaste, had no significant added effect in preventing caries in the primary dentition of these pre-school children (ClinicalTrials.gov number CT01 604109).
caries detection/diagnosis/prevention; child dentistry; clinical studies/trials; enamel; preventive dentistry; remineralization
Temporomandibular arthritis will lengthen a rodent’s meal duration. We hypothesized that meal duration would also lengthen after tooth pulp exposure, suggesting that this behavior could be used to measure tooth nociception. To test this hypothesis, we placed rats in feeding units and subjected 4 anterior mandibular molars to pulp exposure, with and without pre-treatment with the analgesic buprenorphine-HCl. In the first study, male Sprague-Dawley rats were placed in computerized sound-attenuated feeding modules, the pulp of 4 molars on the mandible were exposed, and meal duration was measured for 13 days. In a second study, rats were injected with either the analgesic buprenorphine-HCl or saline every 12 hrs; injections were started one day before pulp exposure. Meal duration was determined before and after treatment. In the first study, pulp exposure significantly increased daily meal duration for 8 days. In the second study, pulp exposure lengthened daily meal duration, but the group that was treated with buprenorphine-HCl showed no significant difference compared with control rats without pulp exposure. Evidence supports that a lengthening in meal duration is a response to tooth nociception and that this nociception can be measured for over a week.
orofacial; pain; meal duration; toothache; necrotic; persistent
We report a clinical study that examines whether HIV infection affects Streptococcus mutans colonization in the oral cavity. Whole stimulated saliva samples were collected from 46 HIV-seropositive individuals and 69 HIV-seronegative control individuals. The level of S. mutans colonization was determined by conventional culture methods. The genotype of S. mutans was compared between 10 HIV-positive individuals before and after highly active antiretroviral therapy (HAART) and 10 non-HIV-infected control individuals. The results were analyzed against viral load, CD4+ and CD8+ T-cell counts, salivary flow rate, and caries status. We observed that S. mutans levels were higher in HIV-infected individuals than in the non-HIV-infected control individuals (p = 0.013). No significant differences in S. mutans genotypes were found between the two groups over the six-month study period, even after HAART. There was a bivariate linear relationship between S. mutans levels and CD8+ counts (r = 0.412; p = 0.007), but not between S. mutans levels and either CD4+ counts or viral load. Furthermore, compared with non-HIV-infected control individuals, HIV-infected individuals experienced lower salivary secretion (p = 0.009) and a positive trend toward more decayed tooth surfaces (p = 0.027). These findings suggest that HIV infection can have a significant effect on the level of S. mutans, but not genotypes.
HIV infections; Streptococcus mutans; genotype; saliva; CD8+ T-lymphocytes; HAART
Few studies have investigated the role of early maternal enabling and psychosocial factors on subsequent adolescent caries experience. In this retrospective cohort study of 224 adolescents, we hypothesized that the causal pathway between early maternal enabling factors (education, cognitive abilities, psychological distress) and adolescent caries experience (DMFT) at age 14 yrs is mediated by maternal psychosocial factors (stress, coping, social support) and adolescent dental behavior/access. Maternal data on socio-demographic, medical, and psychosocial variables were measured when the child was 3, 8, and 14 yrs old. A structural equations model (SEM) evaluated the causal pathway, with latent variables for maternal enabling factors (MEF), stress, coping, and social support. Poor MEF was associated with increased stress and poorer coping when the child was 3 yrs old, which in turn affected adolescent dental visits and behavior. Greater social support at child’s age 3 was directly associated with lower mean DMFT in adolescence. Maternal psychosocial factors measured when children are young are important mediators for adolescent mean DMFT, but these factors measured when children are adolescents are not. Better early and concurrent MEF, however, was associated directly/indirectly (through dental visits and insurance) with adolescent DMFT. Early maternal factors are important predictors for adolescent caries.
dental caries; children; longitudinal; psychosocial; dental behavior; epidemiology
Despite accelerated epithelial closure, oral mucosal wounds exhibit lower levels of VEGF and a more refined angiogenic response than do skin wounds. The specific differences in angiogenesis suggest that skin and oral mucosal wounds may experience dissimilar levels of hypoxia and HIF-1α. Using a model of comparable wounds on murine dorsal skin and tongue, we determined levels of hypoxia and HIF-1α. Skin wounds were found to be significantly more hypoxic and had higher levels of HIF-1α than mucosal wounds. Furthermore, under stressed conditions, skin wounds, but not mucosal wounds, exhibited a further elevation of HIF-1α beyond that of non-stressed levels. To determine if manipulation of oxygen levels might equalize the repair response of each tissue, we exposed mice to hyperbaric oxygen treatment (HBOT) following wounding. HBOT did not significantly change HIF-1α or VEGF expression in either skin or mucosal wounds, nor did it alter wound bed vascularity. These studies suggest that skin wounds have higher levels of hypoxia than do mucosal wounds, along with a differential expression of HIF-1α. Interestingly, modulation of oxygen by HBOT does not ameliorate this difference. These results suggest that differential responses to hypoxia may underlie the distinctive wound-healing phenotypes seen in skin and oral mucosa.
hypoxia-inducible factor-1α; wound and injuries; oxygen; stress; skin; mucous membrane
Levels of prostaglandin E2 (PGE2) and its processing enzyme, prostaglandin-endoperoxide-synthase-2/ cyclooxygenase-2 (PTGS2/COX-2), are elevated in actively progressing periodontal lesions, but suppressed in chronic disease. COX-2 expression is regulated through inflammatory signaling that converges on the mitogen-activated protein kinase (MAPK) pathway. Emerging evidence suggests a role for the inflammatory adaptor protein, ASC/Pycard, in MAPK activation. We postulated that ASC may represent a mediator of the MAPK-mediated regulatory network of PGE2 production. Using RNAi-mediated gene slicing, we demonstrated that ASC regulates COX-2 expression and PGE2 production in THP1 monocytic cells following infection with Porphyromonas gingivalis (Pg). Production of PGE2 did not require the inflammasome adaptor function of ASC, but was dependent on MAPK activation. Furthermore, the MAP kinase kinase kinase CARD domain-containing protein RIPK2 was induced by Pg in an ASC-dependent manner. Reduced ASC and RIPK2 levels were revealed by orthogonal comparison of the expression of the RIPK family in ASC-deficient THP1 cells with that in chronic periodontitis patients. We show that pharmacological inhibition of RIPK2 represses PGE2 secretion, and RNAi-mediated silencing of RIPK2 leads to diminished MAPK activation and PGE2 secretion. These findings identify a novel ASC-RIPK2 axis in the generation of PGE2 that is repressed in patients diagnosed with chronic adult periodontitis.
periodontal disease; COX-2; PTGS2; Porphyromonas gingivalis; ASC; RIPK2
Dental caries is a ubiquitous disease affecting all age groups and segments of the population. It is known that not all caries lesions progress to cavitation, but little is known regarding the progression pattern of caries lesions. This study’s purpose was to evaluate the natural history of dental caries using a standardized, visually based system, the International Caries Detection and Assessment System (ICDAS). The study population consisted of 565 consenting children, who were enrolled and examined at baseline and at regular intervals over 48 months with ICDAS and yearly bitewing radiographs. Of these, 338 children completed all examinations. Not all lesions cavitated at the same rate, differing by surface type and baseline ICDAS severity score and activity status. With increasing severity, the percentage of lesions progressing to cavitation increased: 19%, 32%, 68%, and 66% for ICDAS scores 1, 2, 3, and 4, respectively. Lesions on occlusal surfaces were more likely to cavitate, followed by buccal pits, lingual grooves, proximal surfaces, and buccal and lingual surfaces. Cavitation was more likely on molars, followed by pre-molars and anterior teeth. Predictors of cavitation included age, gender, surfaces and tooth types, and ICDAS severity/activity at baseline. In conclusion, characterization of lesion severity with ICDAS can be a strong predictor of lesion progression to cavitation.
longitudinal study; dental caries; ICDAS; activity; lesion progression; Hispanic
White-spot lesions (WSL) associated with orthodontic appliances are a cosmetic problem and increase risk for cavities. We characterized the microbiota of WSL, accounting for confounding due to gingivitis. Participants were 60 children with fixed appliances, aged between 10 and 19 yrs, half with WSL. Plaque samples were assayed by a 16S rRNA-based microarray (HOMIM) and by PCR. Mean gingival index was positively associated with WSL (p = 0.018). Taxa associated with WSL by microarray included Granulicatella elegans (p = 0.01), Veillonellaceae sp. HOT 155 (p < 0.01), and Bifidobacterium Cluster 1 (p = 0.11), and by qPCR, Streptococcus mutans (p = 0.008) and Scardovia wiggsiae (p = 0.04) Taxa associated with gingivitis by microarray included: Gemella sanguinis (p = 0.002), Actinomyces sp. HOT 448 (p = 0.003), Prevotella cluster IV (p = 0.021), and Streptococcus sp. HOT 071/070 (p = 0.023); and levels of S. mutans (p = 0.02) and Bifidobacteriaceae (p = 0.012) by qPCR. Species’ associations with WSL were minimally changed with adjustment for gingivitis level. Partial least-squares discriminant analysis yielded good discrimination between children with and those without WSL. Granulicatella, Veillonellaceae and Bifidobacteriaceae, in addition to S. mutans and S. wiggsiae, were associated with the presence of WSL in adolescents undergoing orthodontic treatment. Many taxa showed a stronger association with gingivitis than with WSL.
orthodontic; adolescents; white-spot lesions; microbial ecology; Scardovia wiggsiae; HOMIM
The objective of this investigation was to distinguish whether the instruments commonly used for cutting dentin cause degradation in strength or fatigue behavior. Beams of coronal dentin were obtained from unrestored 3rd molars and subjected to either quasi-static or cyclic flexural loading to failure. The surfaces of selected beams were treated with a conventional straight-sided bur or with an abrasive air jet laden with glass particles. Under monotonic loading, there was no difference in the strength or Weibull parameters obtained for the control or treated beams. However, the fatigue strength of dentin receiving bur and air-jet treatments was significantly lower (p ≤ 0.0001) than that of the control. The bur treatment resulted in the largest overall degree of degradation, with nearly 40% reduction in the endurance limit and even more substantial decrease in the fatigue life. The methods currently used for cavity preparations substantially degrade the durability of dentin.
cracked-tooth syndrome; dentin; fatigue; fatigue crack growth; tooth fracture; cutting
A large proportion of pulpal nociceptors are known to contain neuropeptides such as CGRP. However, the projection of non-peptidergic nociceptors to tooth pulp is controversial. Recently, the non- peptidergic subset of nociceptors has been implicated in mechanical pain in the skin. Since mechanical irritation of pulpal nociceptors is critical for evoking tooth pain under pathophysiological conditions, we investigated whether the non-peptidergic afferents project to tooth pulp as potential mechanotransducing afferents. For clear visualization of the non-peptidergic afferents, we took advantage of a recently generated knock-in mouse model in which an axonal tracer, farnesylated green fluorescence protein (GFP), is expressed from the locus of a sensory neuron-specific gene, Mrgprd. In the trigeminal ganglia (TG), we demonstrated that GFP is exclusively expressed in afferents binding to isolectin B4 (IB4), a neurochemical marker of non-peptidergic nociceptors, but is rarely co-localized with CGRP. Retrograde labeling of pulpal afferents demonstrated that a low proportion of pulpal afferents was co-localized with GFP. Immunohistochemical detection of the axonal tracer revealed that GFP-positive afferent terminals were densely projected into the tooth pulp. These results provide convincing evidence that non-peptidergic nociceptors are projected into the tooth pulp and suggest a potential role for these afferents in tooth pain.
pain; nociceptor; dental pulp; immunohistochemistry; transgenic mice; Mas-related receptor MrgD
Circadian rhythms are endogenous self-sustained oscillations with 24-hour periods that regulate diverse physiological and metabolic processes through complex gene regulation by “clock” transcription factors. The oral cavity is bathed by saliva, and its amount and content are modified within regular daily intervals. The clock mechanisms that control salivary production remain unclear. Our objective was to evaluate the expression and periodicity of clock genes in salivary glands. Real-time quantitative RT-PCR, in situ hybridization, and immunohistochemistry were performed to show circadian mRNA and protein expression and localization of key clock genes (Bmal1, Clock, Per1, and Per2), ion and aqua channel genes (Ae2a, Car2, and Aqp5), and salivary gland markers. Clock gene mRNAs and clock proteins were found differentially expressed in the serous acini and duct cells of all major salivary glands. The expression levels of clock genes and Aqp5 showed regular oscillatory patterns under both light/dark and complete-dark conditions. Bmla1 overexpression resulted in increased Aqp5 expression levels. Analysis of our data suggests that salivary glands have a peripheral clock mechanism that functions both in normal light/dark conditions and in the absence of light. This finding may increase our understanding of the control mechanisms of salivary content and flow.
circadian clock; saliva; transcriptional regulation; circadian rhythms; Aqp5; expression pattern
The effect of application mode on polymerization effectiveness of self-etch adhesives with different pHs has rarely been studied. We applied 2 self-etch adhesives—Adper Prompt L-Pop (APLP, pH ~ 0.8) and Adper Easy-Bond (AEB, pH ~ 2.5)—to dentin with or without agitation (dynamic or static application), to investigate photopolymerization efficacy on dentin, and to understand the role of chemical interaction/reaction between adhesives and dentin. Micro-Raman spectra and imaging were acquired across the dentin/adhesive (D/A) interface. The degree of conversion (DC) of each adhesive as a function of position was calculated. SEM-EDS was used to obtain the elemental distribution along the interface. Photopolymerization efficacies of the two self-etch adhesives on dentin were apparently different. APLP exhibited decreasing DCs as the distance from the D/A interface became greater for both application modes, while the DCs for the dynamic mode were much higher than those for the static mode. As for AEB, the DCs remained almost constant across the adhesive layer and showed no significant difference between two modes. Raman spectral analysis disclosed that the chemical interaction between dentin and adhesives was responsible for the observations. We also verified this by tracking the distribution of the elements Ca and P in the adhesive layers.
self-etch adhesives; pH; degree of conversion; micro-Raman; demineralization; imaging
The purpose of this study was to identify socio-economic inequalities in regular dental attendance throughout the life-course. The analyses relied on data from SHARE (waves 1 to 3 of the Survey of Health, Ageing, and Retirement in Europe), which includes retrospective information on life-course dental attendance of 26,525 persons currently aged 50 years or greater from 13 European countries (Austria, Poland, Spain, Italy, the Netherlands, Belgium, Greece, the Czech Republic, France, Denmark, Switzerland, Germany, and Sweden). Inequalities in dental attendance were assessed by means of Concentration Indices. Socio-economic disparities in regular dental attendance were identified as early as childhood. Moreover, higher educational attainment resulted in increased probabilities of regular dental attendance throughout subsequent life-years in all nations. In most countries, inequality levels remained relatively inelastic throughout the life-course. These findings suggest that a considerable proportion of inequalities in dental care use is already established at childhood and persists throughout the life-course.
socio-economic disparities; dental care use; lifecycle analysis; elderly populations; health policy; health care economics and organizations
Pathological shifts of the human microbiome are characteristic of many diseases, including chronic periodontitis. To date, there is limited evidence on host genetic risk loci associated with periodontal pathogen colonization. We conducted a genome-wide association (GWA) study among 1,020 white participants of the Atherosclerosis Risk in Communities Study, whose periodontal diagnosis ranged from healthy to severe chronic periodontitis, and for whom “checkerboard” DNA-DNA hybridization quantification of 8 periodontal pathogens was performed. We examined 3 traits: “high red” and “high orange” bacterial complexes, and “high” Aggregatibacter actinomycetemcomitans (Aa) colonization. Genotyping was performed on the Affymetrix 6.0 platform. Imputation to 2.5 million markers was based on HapMap II-CEU, and a multiple-test correction was applied (genome-wide threshold of p < 5 × 10−8). We detected no genome-wide significant signals. However, 13 loci, including KCNK1, FBXO38, UHRF2, IL33, RUNX2, TRPS1, CAMTA1, and VAMP3, provided suggestive evidence (p < 5 × 10−6) of association. All associations reported for “red” and “orange” complex microbiota, but not for Aa, had the same effect direction in a second sample of 123 African-American participants. None of these polymorphisms was associated with periodontitis diagnosis. Investigations replicating these findings may lead to an improved understanding of the complex nature of host-microbiome interactions that characterizes states of health and disease.
bacteria; infection; chronic periodontitis; genetics; genome-wide association studies; dentistry
The NIDCR-supported Practice-based Research Network initiative presents dentistry with an unprecedented opportunity by providing a pathway for modifying and advancing the profession. It encourages practitioner participation in the transfer of science into practice for the improvement of patient care. PBRNs vary in infrastructure and design, and sustaining themselves in the long term may involve clinical trial validation by regulatory agencies. This paper discusses the PBRN concept in general and uses the New York University College of Dentistry’s Practitioners Engaged in Applied Research and Learning (PEARL) Network as a model to improve patient outcomes. The PEARL Network is structured to ensure generalizability of results, data integrity, and to provide an infrastructure in which scientists can address clinical practitioner research interests. PEARL evaluates new technologies, conducts comparative effectiveness research, participates in multidisciplinary clinical studies, helps evaluate alternative models of healthcare, educates and trains future clinical faculty for academic positions, expands continuing education to include “benchmarking” as a form of continuous feedback to practitioners, adds value to dental schools’ educational programs, and collaborates with the oral health care and pharmaceutical industries and medical PBRNs to advance the dental profession and further the integration of dental research and practice into contemporary healthcare (NCT00867997, NCT01268605).
Practice-based Research Network; good clinical practice; clinical studies; patient-reported outcomes; Comparative Effectiveness Research (CER); Evidence-based Dentistry (EBD)
The aim of the study was to investigate the efficacy of the use of xylitol-containing tooth-wipes in preventing dental caries in young children. In a double-blinded randomized controlled clinical trial, 44 mothers with active caries and their 6- to 35-month-old children were randomized to xylitol-wipe or placebo-wipe groups. The children’s caries scores were recorded at baseline and 1 year. Salivary levels of mutans streptococci and lactobacilli were enumerated at baseline, 3, 6, and 12 months. Data were analyzed by intent-to-treat modeling with imputation for caries lesions and a linear mixed-effect model for bacterial levels. Significantly fewer children in the xylitol-wipe group had new caries lesions at 1 year compared with those in the placebo-wipe group (P < 0.05). No significant differences between the two groups were observed in levels of mutans streptococci and lactobacilli at all time-points. Daily xylitol-wipe application significantly reduced the caries incidence in young children as compared with wipes without xylitol, suggesting that the use of xylitol wipes may be a useful adjunct for caries control in infants (Clinicaltrials.gov registration number CT01468727).
early childhood caries; xylitol; clinical studies/trials; mutans streptococci; lactobacilli; transmission
Focusing public insurance programs on interceptive orthodontics (IO) may increase
access for low-income children. This report presents outcomes from a randomized
clinical trial (RCT) comparing IO with comprehensive orthodontics (CO) in Medicaid
One hundred seventy pre-adolescents with Medicaid-eligible malocclusions were
randomized to IO (n = 86) followed by observation (OBS) or OBS followed by CO (n =
84). One hundred thirty-four completed the trial. Models at pre-treatment (baseline)
and following ≤ 2 years of intervention and 2 years of OBS (48 mos) were scored by
calibrated examiners using the Peer Assessment Rating (PAR) and Index of Complexity,
Outcome and Need (ICON). Overall outcomes and clinically meaningful categorical ICON
data on need/acceptability, complexity, and improvement were compared.
At baseline, groups were balanced by age, gender, ethnicity, and PAR/ICON scores.
Most were minorities. Most (77%) were rated as difficult-to-very difficult. Scores
improved significantly for both groups, but CO more than IO (PAR, 18.6 [95%CI 15.1,
22.1] vs.10.1 [95%CI 6.7, 13.4]; ICON, 44.8 [95% CI 39.7, 49.9]
vs. 35.2 [95%CI 29.7, 40.6], respectively).
On average, IO is effective at reducing malocclusions in Medicaid patients, but less
than CO. (ClinicalTrials.gov number CT00067379)
access to care; orthodontic therapy; occlusion; patient outcomes; evidence-based dentistry/health care
Cytokines are critical mediators of inflammation and host defenses. Regulation of cytokines can occur at various stages of gene expression, including transcription, mRNA export, and post- transcriptional and translational levels. Among these modes of regulation, post-transcriptional regulation has been shown to play a vital role in controlling the expression of cytokines by modulating mRNA stability. The stability of cytokine mRNAs, including TNFα, IL-6, and IL-8, has been reported to be altered by the presence of AU-rich elements (AREs) located in the 3′-untranslated regions (3′UTRs) of the mRNAs. Numerous RNA-binding proteins and microRNAs bind to these 3′UTRs to regulate the stability and/or translation of the mRNAs. Thus, this paper describes the cooperative function between RNA-binding proteins and miRNAs and how they regulate AU-rich elements containing cytokine mRNA stability/degradation and translation. These mRNA control mechanisms can potentially influence inflammation as it relates to oral biology, including periodontal diseases and oral pharyngeal cancer progression.
inflammation; oral cancer; mouth neoplasms; periodontal diseases; RNA stability; microRNAs