Journal of Dental Research

Birth cohorts are those among observational studies that provide understanding of the natural history and causality of diseases since early in life. Discussions during an International Association for Dental Research symposium in London, United Kingdom, in 2018, followed by a workshop in Bangkok, Thailand, in 2019, concluded that there are few birth cohort studies that consider oral health and that a broader discussion on similarities and differences among those studies would be valuable. This article aims to 1) bring together available long-term data of oral health birth cohort studies from the low, middle, and high-income countries worldwide and 2) describe similarities and differences among these studies. This work comprises 15 studies from all 5 continents. The most studied dental conditions and exposures are identified; findings are summarized; and methodological differences and similarities among studies are presented. Methodological strengths and weaknesses are also highlighted. Findings are summarized in 1) the negative impact of detrimental socioeconomic status on oral health changes over time, 2) the role of unfavorable patterns of dental visiting on oral health, 3) associations between general and oral health, 4) nutritional and dietary effects on oral health, and 5) intergenerational influences on oral health. Dental caries and dental visiting patterns have been recorded in all studies. Sources of fluoride exposure have been documented in most of the more recent studies. Despite some methodological differences in the way that the exposures and outcomes were measured, some findings are consistent. Predictive models have been used with caries risk tools, periodontitis occurrence, and permanent dentition orthodontic treatment need. The next steps of the group’s work are as follows: 1) establishing a consortium of oral health birth cohort studies, 2) conducting a scoping review, 3) exploring opportunities for pooled data analyses to answer pressing research questions, and 4) promoting and enabling the development of the next generation of oral health researchers.

The packaging of DNA around nucleosomes exerts dynamic control over eukaryotic gene expression either by granting access to the transcriptional machinery in an open chromatin state or by silencing transcription via chromatin compaction. Histone methylation modification affects chromatin through the addition of methyl groups to lysine or arginine residues of histones H3 and H4 by means of histone methyl transferases or histone demethylases. Changes in histone methylation state modulate periodontal gene expression and have profound effects on periodontal development, health, and therapy. At the onset of periodontal development, progenitor cell populations such as dental follicle cells are characterized by an open H3K4me3 chromatin mark on RUNX2, MSX2, and DLX5 gene promoters. During further development, periodontal progenitor differentiation undergoes a global switch from the H3K4me3 active methyl mark to the H3K27me3 repressive mark. When compared with dental pulp cells, periodontal neural crest lineage differentiation is characterized by repressive H3K9me3 and H3K27me3 marks on typical dentinogenesis-related genes. Inflammatory conditions as they occur during periodontal disease result in unique histone methylation signatures in affected cell populations, including repressive H3K9me3 and H3K27me3 histone marks on extracellular matrix gene promoters and active H3K4me3 marks on interleukin, defensin, and chemokine gene promoters, facilitating a rapid inflammatory response to microbial pathogens. The inflammation-induced repression of chromatin on extracellular matrix gene promoters presents a therapeutic opportunity for the application of histone methylation inhibitors capable of inhibiting suppressive trimethylation marks. Furthermore, inhibition of chromatin coregulators through interference with key inflammatory mediators such as NF-kB by means of methyltransferase inhibitors provides another avenue to halt the exacerbation of the inflammatory response in periodontal tissues. In conclusion, histone methylation dynamics play an intricate role in the fine-tuning of chromatin states during periodontal development and harbor yet-to-be-realized potential for the treatment of periodontal disease.

This study aimed to measure the magnitude of education-related inequalities in the use of dental services among older adults (aged 50 y or older) from a sizable multicountry sample of 23 upper-middle- and high-income countries. This study used cross-sectional data from nationally representative surveys of people aged 50 y and over. Countries included in the Health and Retirement Study surveys were the following: Brazil, China, South Korea, Mexico, United States, Austria, Belgium, Croatia, Czech Republic, Denmark, Estonia, France, Germany, Greece, Italy, Israel, Luxembourg, Poland, Portugal, Slovenia, Spain, Sweden, and Switzerland. The dependent variable was the use of dental services, based on the self-report of having had a dental visit within the previous year, except for the United States and South Korea, which used 2-y recall periods. Educational level was used as the measure of socioeconomic position and was standardized across countries. Multivariate logistic regression modeling was used to evaluate the factors associated with the use of dental services, and the magnitude of education inequalities in the use of dental services was assessed using the slope index of inequality (SII) to measure absolute inequalities and the relative index of inequality for relative inequalities. The pooled prevalence of the use of dental services was 31.7% and ranged from 18.7% in China to 81.2% in Sweden. In the overall sample, the absolute difference in the prevalence of use between the lowest and highest educational groups was 20 percentage points. SII was significant for all countries except Portugal. Relative educational inequalities were significant for all countries and ranged from 3.2 in Poland to 1.2 in Sweden. There were significant education-related inequalities in the use of dental care by older adults in all countries. Monitoring these inequalities is critical to the planning and delivery of dental services.

The objective of this study was to compare postsurgical outcomes of resective treatment for peri-implantitis with and without implant surface modification (implantoplasty [IP]). This was accomplished by a retrospective analysis with data from patients with ≥1 implant who were surgically treated for peri-implantitis by resective therapy. Patients were divided into 2 groups regarding treatment approach: IP (test) and no IP (control). Retrospective data were obtained after implant placement (T0) and the day of peri-implantitis surgical treatment (T1). Patients were then recalled (≥1 y after T1) for clinical and radiographic examination (T2). The findings were conclusive. A total of 41 patients (68 implants; mean ± SD follow-up, 41.6 ± 24.4 mo) were included in this study. The survival rate at the implant level was 90% in the test group and 81.6% in the control group (P > 0.05). Multilevel regression analysis showed that the probability of implant failure was influenced by marginal bone loss (MBL) at T1 and not surgical modality. For example, peri-implantitis defects ≥50% and 25% to 50% MBL were 18.6 and 8.86 times more likely to lose the implant, respectively, when compared with <25% MBL. Nonetheless, MBL changes were similar in the test and control groups (P = 0.592). Similarly, changes in bleeding on probing, probing pocket depth, and suppuration at T2 did not differ between groups (P > 0.05). Multilevel regression analysis indicated that clinical improvement of these parameters was influenced by the number of supportive peri-implant therapy visits (P < 0.01). The results demonstrate little difference between the procedures. Regardless of the implant surface modification (IP) being performed or not, the survival rate of implants treated for peri-implantitis was primarily influenced by the amount of bone loss at the time of treatment. Other clinical parameters (MBL, probing pocket depth, bleeding on probing, suppuration) were influenced by the frequency of supportive peri-implant therapy visits and not by the IP procedure (ClinicalTrials.gov NCT04259840).

Despite their prevalence and burdens, oral diseases are neglected in universal health coverage. In Japan, a 30% copayment (out of pocket) by the user and a 70% contribution by Japan’s universal health insurance (JUHI) are required for dental and medical services. From the age of 70 y, an additional 10% is offered by JUHI (copayment, 20%; JUHI, 80%). This study aimed to investigate the effect of cost on dental service use among older adults under the current JUHI system. A regression discontinuity quasi-experimental method was used to investigate the causal effect of the JUHI discount policy on dental visits based on cross-sectional data. Data were derived from the 2016 Japan Gerontological Evaluation Study. This analysis contained 7,161 participants who used JUHI, were aged 68 to 73 y, and responded to questions regarding past dental visits. Analyses were controlled for age, sex, number of teeth, and equalized household income. Mean ± SD age was 72.1 ± 0.79 y for the discount-eligible group and 68.9 ± 0.78 y for the noneligible group. During the past 12 mo, significantly more discount-eligible participants had visited dental services than noneligible participants (66.0% vs. 62.1% for treatment visits, 57.7% vs. 53.1% for checkups). After controlling for covariates, the effect of discount eligibility was significant on dental treatment visits (odds ratio [OR], 1.36; 95% CI, 1.32 to 1.40) and dental checkups (OR, 1.49; 95% CI, 1.44 to 1.54) in the regression discontinuity analysis. Similar findings were observed in triangular kernel-weighted models (OR, 1.38 [95% CI, 1.34 to 1.44]; OR, 1.52 [95% CI, 1.47 to 1.56], respectively). JUHI copayment discount policy increases oral health service utilization among older Japanese. The price elasticity for dental checkup visits appears to be higher than for dental treatment visits. Hence, reforming the universal health coverage system to improve the affordability of relatively inexpensive preventive care could increase dental service utilization in Japan.

The purpose of this study was to develop a diagnostic tool to automatically detect temporomandibular joint osteoarthritis (TMJOA) from cone beam computed tomography (CBCT) images with artificial intelligence. CBCT images of patients diagnosed with temporomandibular disorder were included for image preparation. Single-shot detection, an object detection model, was trained with 3,514 sagittal CBCT images of the temporomandibular joint that showed signs of osseous changes in the mandibular condyle. The region of interest (condylar head) was defined and classified into 2 categories—indeterminate for TMJOA and TMJOA—according to image analysis criteria for the diagnosis of temporomandibular disorder. The model was tested with 2 sets of 300 images in total. The average accuracy, precision, recall, and F1 score over the 2 test sets were 0.86, 0.85, 0.84, and 0.84, respectively. Automated detection of TMJOA from sagittal CBCT images is possible by using a deep neural networks model. It may be used to support clinicians with diagnosis and decision making for treatments of TMJOA.

Secondary caries caused by dental plaque is one of the major reasons for the high failure rate of resin composite restoration. Although antimicrobial agent–modified dental restoration systems have been researched for years, few reported intelligent anticaries materials could respond to the change of the oral environment and help keep oral eubiosis. Herein, we report tertiary amine (TA)–modified resin adhesives (TA@RAs) with pH-responsive antibacterial effect to reduce the occurrence of secondary caries. Two kinds of newly designed TA monomers were synthesized: DMAEM (dodecylmethylaminoethyl methacrylate) and HMAEM (hexadecylmethylaminoethyl methacrylate). In the minimum inhibitory concentration and minimum bactericidal concentration test against Streptococcus mutans, Streptococcus sanguinis, and Streptococcus gordonii, they exhibited antibacterial effect only in acidic medium, which preliminarily verified the acid-activated effect of TAs. Then DMAEM and HMAEM were incorporated into adhesive resin at the mass fraction of 5%, yielding TA@RAs. In vivo and in vitro tests showed that the mechanical properties and biocompatibility of the adhesive were not affected. A S. mutans biofilm model in acidic and neutral medium was used and confirmed that TA@RAs could respond to the critical pH value of de-/remineralization and acquire reversible antibiofilm effect via the protonation and deprotonation of TAs. Meanwhile, the stability of antibacterial effect was confirmed via a 5-d pH-cycling experiment and a saliva-derived biofilm aging model. Furthermore, 16S rRNA gene sequencing showed that TA@RAs could increase the diversity of the saliva-derived biofilms, which implied that the novel materials could help regulate the microbial community to a healthy one. Finally, an in vitro demineralization model and in vivo secondary caries model were applied and demonstrated that TA@RAs could prevent secondary dental caries effectively. In summary, the reversible pH-responsive and non–drug release antibacterial resin adhesives ingeniously overcome the defect of the present materials and hold great promise for clinical application.

During the mandibular condylar growth, the absorption of calcified cartilage matrix induced by osteoclasts is crucial for the continuous endochondral osteogenesis. Meanwhile, recent studies showed that subchondral bone resided within the low-oxygen microenvironment, and our previous study revealed that hypoxia-inducible transcription factor 1α (HIF-1α) promoted osteoclastogenesis under hypoxia. However, whether HIF-1α regulates the function of osteoclasts in the mandibular condyle cartilage remains elusive. Our study indicated that severe deformity of the mandibular condyle was displayed in 10-wk-old osteoclast-specific HIF-1α conditional knockout (CKO) mice, accompanied by shortened length of condylar process and disorganized fibrocartilage. In 1-, 2-, and 4-wk-old CKO mice, the size of the hypertrophic layer and chondrocytic layer was significantly thickened. In the chondrocytic layer, chondrocytes were atrophied, showing a form of apoptosis in 4-wk-old CKO mice. Furthermore, an increase in the thickness of the fibrous and proliferating layer was observed in 10-wk-old CKO mice, as well as a significant decrease in that of the chondrocytic and hypertrophic chondrocyte layers. Interestingly, the articular surface of the condylar process abnormally presented a horizontal concave shape, and a disk-like acellular connective tissue appeared. In addition, genetic ablation of HIF-1α blunted cartilage matrix loss by subchondral osteoclast deficiency, resulting in a high subchondral bone mass phenotype, accompanied with a decreased number of blood vessels, alkaline phosphatase staining, and vascular endothelial growth factor (VEGF) expression. Mechanistically, the number of osteoclasts in the center of the condyle in CKO mice was significantly reduced by attenuated expression of adenosine 5′-monophosphate-activated protein kinase (AMPK) signaling. These findings reveal a novel influence of HIF-1α function in osteoclasts on maintenance of osteoclast-induced resorption of calcified cartilage matrix via AMPK signaling, as well as subchondral bone formation through VEGF-dependent angiogenesis in bone marrow.

Clefting of the secondary palate is one of the most common congenital anomalies, and the multiple corrective surgeries that individuals with isolated cleft palate undergo are associated with major costs and morbidities. Secondary palate development is a complex, multistep process that includes the elevation of the palatal shelves from a vertical to horizontal position, a process that is not well understood. The Hippo signaling cascade is a mechanosensory pathway that regulates morphogenesis, homeostasis, and regeneration by controlling cell proliferation, apoptosis, and differentiation, primarily via negative regulation of the downstream effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). We deleted Yap/Taz throughout the palatal shelf mesenchyme as well as specifically in the posterior palatal shelf mesenchyme, using the Osr2^Cre and Col2^Cre drivers, respectively, which resulted in palatal shelf elevation delay and clefting of the secondary palate. In addition, the deletion resulted in undersized bones of the secondary palate. We next determined downstream targets of YAP/TAZ in the posterior palatal shelves, which included Ibsp and Phex, genes involved in mineralization, and Loxl4, which encodes a lysyl oxidase that catalyzes collagen crosslinking. Ibsp, Phex, and Loxl4 were expressed at decreased levels in the ossification region in the posterior palatal shelf mesenchyme upon deletion of Yap/Taz. Furthermore, collagen levels were decreased specifically in the same region prior to elevation. Thus, our data suggest that YAP/TAZ may regulate collagen crosslinking in the palatal shelf mesenchyme, thus controlling palatal shelf elevation, as well as mineralization of the bones of the secondary palate.

In humans, ankyloglossia and cleft palate are common congenital craniofacial anomalies, and these are regulated by a complex gene regulatory network. Understanding the genetic underpinnings of ankyloglossia and cleft palate will be an important step toward rational treatment of these complex anomalies. We inactivated the Sry (sex-determining region Y)–box 2 (Sox2) gene in the developing oral epithelium, including the periderm, a transient structure that prevents abnormal oral adhesions during development. This resulted in ankyloglossia and cleft palate with 100% penetrance in embryos examined after embryonic day 14.5. In Sox2 conditional knockout embryos, the oral epithelium failed to differentiate, as demonstrated by the lack of keratin 6, a marker of the periderm. Further examination revealed that the adhesion of the tongue and mandible expressed the epithelial markers E-Cad and P63. The expanded epithelia are Sox9-, Pitx2-, and Tbx1-positive cells, which are markers of the dental epithelium; thus, the dental epithelium contributes to the development of oral adhesions. Furthermore, we found that Sox2 is required for palatal shelf extension, as well as for the formation of palatal rugae, which are signaling centers that regulate palatogenesis. In conclusion, the deletion of Sox2 in oral epithelium disrupts palatal shelf extension, palatal rugae formation, tooth development, and periderm formation. The periderm is required to inhibit oral adhesions and ankyloglossia, which is regulated by Sox2. In addition, oral adhesions occur through an expanded dental epithelial layer that inhibits epithelial invagination and incisor development. This process may contribute to dental anomalies due to ankyloglossia.