Journal of Dental Research最新文献

The speech of the AADOCR President-Elect Alexandre R. Vieira given at the opening ceremony of the 52nd Annual Meeting and Exhibition in Portland, March 15, 2023.

Periodontitis is the utmost common chronic oral disease that exhibits intense susceptibility to aging. Aging is characterized by persistent sterile low-grade inflammation, leading to age-related periodontal complications represented by alveolar bone loss. Currently, forkhead transcription factor O1 (FoxO1) is generally believed to have a significant role in body development, senescence, cell viability, and oxidative stress in numerous organs and cells. However, the role of this transcription factor in mediating age-related alveolar bone resorption has not been examined. In this study, FoxO1 deficiency was discovered to have a beneficial correlation with halting the progression of alveolar bone resorption in aged mice. To further investigate the function of FoxO1 in age-related alveolar bone resorption, osteoblastic-specific FoxO1 knockout mice were generated, leading to an amelioration in alveolar bone loss compared to aged-matched wild-type mice, manifested as enhanced osteogenic potential. Mechanistically, we identified enhancement of the NLRP3 inflammasome signaling in FoxO1-deficient osteoblasts in the high dose of reactive oxygen species. Concordant with our study, MCC950, a specific inhibitor of NLRP3 inflammasome, greatly rescued osteoblast differentiation under oxidative stress. Our data shed light on the manifestations of FoxO1 depletion in osteoblasts and propose a possible mechanism for the therapy of age-related alveolar bone loss.

Dental caries lesions are a clinical manifestation of disease, preceded by microbial dysbiosis, which is poorly characterized and thought to be associated with saccharolytic taxa. Here, we assessed the associations between the oral microbiome of children and various caries risk factors such as demographics and behavioral and clinical data across early childhood and characterized over time the salivary and dental plaque microbiome of children before clinical diagnosis of caries lesions. Children (N = 266) were examined clinically at ~1, 2.5, 4, and 6.5 y of age. The microbiome samples were collected at 1, 2.5, and 4 y. Caries groups consisted of children who remained caries free (International Caries Detection and Assessment System [ICDAS] = 0) at all time points (CFAT) (n = 50); children diagnosed with caries (ICDAS ≥ 1) at 6.5 y (C6.5), 4 y (C4), or 2.5 y of age (C2.5); and children with early caries or advanced caries lesions at specific time points. Microbial community analyses were performed on zero-radius operational taxonomic units (zOTUs) obtained from V4 of 16S ribosomal RNA gene amplicon sequences. The oral microbiome of the children was affected by various factors, including antibiotic use, demographics, and dietary habits of the children and their caregivers. At all time points, various risk factors explained more of the variation in the dental plaque microbiome than in saliva. At 1 y, composition of saliva of the C4 group differed from that of the CFAT group, while at 2.5 y, this difference was observed only in plaque. At 4 y, multiple salivary and plaque zOTUs of genera Prevotella and Leptotrichia were significantly higher in samples of the C6.5 group than those of the CFAT group. In conclusion, up to 3 y prior to clinical caries detection, the oral microbial communities were already in a state of dysbiosis that was dominated by proteolytic taxa. Plaque discriminated dysbiotic oral ecosystems from healthy ones better than saliva.

Diabetes mellitus (DM) is a recognized risk factor for dementia, and increasing evidence shows that tooth loss is associated with cognitive impairment and dementia. However, the effect of the co-occurrence of DM and edentulism on cognitive decline is understudied. This 12-y cohort study aimed to assess the effect of the co-occurrence of DM and edentulism on cognitive decline and examine whether the effect differs by age group. Data were drawn from the 2006 to 2018 Health and Retirement Study. The study sample included 5,440 older adults aged 65 to 74 y, 3,300 aged 75 to 84 y, and 1,208 aged 85 y or older. Linear mixed-effect regression was employed to model the rates of cognitive decline stratified by age cohorts. Compared with their counterparts with neither DM nor edentulism at baseline, older adults aged 65 to 74 y (β = -1.12; 95% confidence interval [CI], -1.56 to -0.65; P < 0.001) and those aged 75 to 84 y with both conditions (β = -1.35; 95% CI, -2.09 to -0.61; P < 0.001) had a worse cognitive function. For the rate of cognitive decline, compared to those with neither condition from the same age cohort, older adults aged 65 to 74 y with both conditions declined at a higher rate (β = -0.15; 95% CI, -0.20 to -0.10; P < 0.001). Having DM alone led to an accelerated cognitive decline in older adults aged 65 to 74 y (β = -0.09; 95% CI, -0.13 to -0.05; P < 0.001); having edentulism alone led to an accelerated decline in older adults aged 65 to 74 y (β = -0.13; 95% CI, -0.17 to -0.08; P < 0.001) and older adults aged 75 to 84 (β = -0.10; 95% CI, -0.17 to -0.03; P < 0.01). Our study finds the co-occurrence of DM and edentulism led to a worse cognitive function and a faster cognitive decline in older adults aged 65 to 74 y.

Water residue and replacement difficulty cause insufficient adhesive infiltration in demineralized dentin matrix (DDM), which produces a defective hybrid layer and thus a bonding durability problem, severely plaguing adhesive dentistry for decades. In this study, we propose that the unique properties of a highly hydrated interface of the porous DDM can give rise to 1 new type of interface, confined liquid water, which accounts for most of the residue water and may be the main cause of insufficient infiltration. To prove our hypothesis, 3 metal ions with increasing binding affinity and complex stability (Na⁺, Ca²⁺, and Cu²⁺) were introduced respectively to coordinate negatively charged groups such as -PO₄^3-, -COO^- abundant in the DDM interface. Strong chelation of Ca²⁺ and Cu²⁺ rapidly released the confined water, significantly improving penetration of hydrophobic adhesive monomers, while Na⁺ had little effect. A significant decrease of defects in the hybrid layer and a much decreased modulus gap between the hybrid layer and the adhesive layer greatly optimized the microstructure and micromechanical properties of the tooth-resin bonding interface, thus improving the effectiveness and durability of dentin bonding substantially. This study paves the way for a solution to the core scientific issue of contemporary adhesive dentistry: water residue and replacement in dentin bonding, both theoretically and practically.

Nano-hydroxyapatite (nHAP) is considered a biocompatible agent that promotes the remineralization of dental hard tissue; however, its antibacterial efficacy is under scientific discussion. Therefore, this investigation aimed to specify the inhibitory effects of disaggregated nano-hydroxyapatite (DnHAP) on regrown biofilms and demineralization. Regrown biofilm models of single-species (Streptococcus mutans), dual-species (S. mutans and Candida albicans), and saliva-derived microcosm biofilms were established in vitro. Repeat treatment with DnHAP was applied to biofilms. The viability, lactic acid, biofilm structure, biomass, the inhibitory effect of demineralization, and virulence factors' expression were determined. In addition, the biofilm microbial community was analyzed by 16S ribosomal RNA gene sequencing. DnHAP inhibited metabolism, lactic acid production, biomass, and water-insoluble polysaccharide production (P < 0.05) of regrown single/dual-species biofilms. Concerning the saliva-derived biofilms, samples treated with DnHAP showed lower biofilm metabolic activity without significant differences from samples treated with sterile deionized water (P > 0.05); in addition, saliva-derived biofilms treated with DnHAP exhibited lower lactic acid production (P < 0.05). The demineralization of bovine enamel was the lowest in the DnHAP group, as detected by transverse microradiography, and the lesion depth and volume decreased significantly (P < 0.05). The application of DnHAP did not change the diversity of regrown saliva-derived microcosm biofilms. In conclusion, this investigation showed that DnHAP could be a promising solution for the management of regrown biofilms to combat dental caries.

Social participation prevents social isolation and loneliness among older adults while having numerous positive effects on their health and well-being in rapidly aging societies. We aimed to estimate the effect of retaining more natural teeth on social participation among older adults in Japan. The analysis used longitudinal data from 24,872 participants in the Japan Gerontological Evaluation Study (2010, 2013, and 2016). We employed a longitudinal modified treatment policy approach to determine the effect of several hypothetical scenarios (preventive scenarios and tooth loss scenarios) on frequent social participation (1 = at least once a week/0 = less than once a week) after a 6-y follow-up. The corresponding statistical parameters were estimated using targeted minimum loss-based estimation (TMLE) method. Number of teeth category (edentate/1-9/10-19/≥20) was treated as a time-varying exposure, and the outcome estimates were adjusted for time-varying (income, self-rated health, marital status, instrumental activities of daily living, vision loss, hearing loss, major comorbidities, and number of household members) and time-invariant covariates (age, sex, education, baseline social participation). Less frequent social participation was associated with older age, male sex, lower income, low educational attainment, and poor self-rated health at the baseline. Social participation improved when tooth loss prevention scenarios were emulated. The best preventive scenario (i.e., maintaining ≥20 teeth among each participant) improved social participation by 8% (risk ratio [RR] = 1.08; 95% confidence interval [CI], 1.05-1.11). Emulated tooth loss scenarios gradually decreased social participation. A hypothetical scenario in which all the participants were edentate throughout the follow-up period resulted in a 11% (RR = 0.89; 95% CI, 0.84-0.94) reduction in social participation. Subsequent tooth loss scenarios showed 8% (RR = 0.92; 95% CI, 0.88-0.95), 6% (RR = 0.94; 95% CI, 0.91-0.97), and 4% (RR = 0.96; 95% CI, 0.93-0.98) reductions, respectively. Thus, among Japanese older adults, retaining a higher number of teeth positively affects their social participation, whereas being edentate or having a relatively lower number of teeth negatively affects their social participation.

The single-nucleotide polymorphism (SNP) rs2235371 (IRF6 V274I) is associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Han Chinese and other populations but appears to be without a functional effect. To find the common etiologic variant or variants within the haplotype tagged by rs2235371, we carried out targeted sequencing of an interval containing IRF6 in 159 Han Chinese with NSCL/P. This study revealed that the SNP rs12403599, within the IRF6 promoter, is associated with all phenotypes of NSCL/P, especially nonsyndromic cleft lip (NSCLO) and a subphenotype of it, microform cleft lip (MCL). This association was replicated in 2 additional much larger cohorts of cases and controls from the Han Chinese. Conditional logistic analysis indicated that association of rs2235371 with NSCL/P was lost if rs12403599 was excluded. rs12403599 contributes the most risk to MCL: its G allele is responsible for 38.47% of the genetic contribution to MCL, and the odds ratios of G/C and G/G genotypes were 2.91 and 6.58, respectively, for MCL. To test if rs12403599 is functional, we carried out reporter assays in a fetal oral epithelium cells (GMSM-K). Unexpectedly, the risk allele G yielded higher promoter activity in GMSM-K. Consistent with the reporter studies, expression of IRF6 in lip tissues from NSCLO and MCL patients with the G/G phenotype was higher than in those from patients with the C/C phenotype. These results indicate that rs12403599 is tagging the risk haplotype for NSCL/P better than rs2235371 in Han Chinese and supports investigation of the mechanisms by which the allele of rs12403599 affects IRF6 expression and tests of this association in different populations.

Growing evidence demonstrates the relationship between periodontitis and atherosclerotic cardiovascular diseases. The periodontal pathogen Porphyromonas gingivalis (Pg) has been shown to contribute to the progression of atherosclerosis. Cyclic diadenylate monophosphate (c-di-AMP) has been widely studied as an immune adjuvant for tumor immunotherapy, given its ability to activate the stimulator of interferon genes (STING) and regulate trained immunity. This study sought to elucidate the role of c-di-AMP in Pg-associated atherosclerosis. Periodontitis and atherosclerosis mouse models were established by ligature application around maxillary second molars and feeding ApoE knockout mice with a high-fat diet. We found that periodontitis and atherosclerosis were more severe in mice exposed to Pg than mice that underwent ligature placement only, while prophylactic treatment with c-di-AMP activated trained immunity and elicited significant alleviation of alveolar bone resorption, as well as reduced blood lipid levels and atherosclerotic plaque accumulation. After 3 mo of intervention, c-di-AMP limited the elevation of cytokines interleukin (IL)-6, IL-1β, tumor necrosis factor α, and interferon β; extracellular matrix remodeling enzymes MMP-2 and MMP-9; and adhesion molecules ICAM-1 and VCAM-1 gene expression. The mechanism underlying Pg-aggravated atherosclerosis may be attributed to changes in microbiota composition in oral and aortic plaques and excess inflammatory response, whereas c-di-AMP could prevent the effects of Pg infection due to its potential ability to activate trained immunity and regulate microecological balance. Our findings suggest a positive role of c-di-AMP in alleviating Pg-aggravated atherosclerosis by regulating the immune response and influencing the local microenvironment.