Journal of dental research最新文献

Sjögren's disease (SjD), an autoimmune inflammatory disease, is associated with reduced androgen levels. Testosterone replacement therapy alleviates SjD progression, but the exact mode of action is unclear and adverse effects are reported. Our present study found that dihydrotestosterone (DHT) enhances the transcription and expression of aquaporin 5 (AQP5) in human salivary gland epithelial cells via androgen receptor (AR) signaling. The DHT/AR complex binds to the androgen response element of the AQP5 promoter, upregulating AQP5 expression. Using orchiectomized mice, we observed that reduced levels of DHT resulted in hyposalivation and SjD progression. By screening compounds with similar structures to DHT, we identified that DHT-like ginsenoside Rg3, a natural product, upregulates AQP5 expression in salivary gland epithelial cells via binding with AR. The Rg3/AR complex acts like DHT/AR and binds to the androgen response element of the AQP5 promoter to promote AQP5 transcription in salivary gland epithelial cells. Gavage of Rg3 restored saliva secretion and submandibular gland morphology in orchiectomized and nonobese diabetic mice. Transcriptome analysis revealed that Rg3 treatment upregulates saliva secretion-related signaling and downregulates inflammation and immune activation-related signaling in the submandibular glands of orchiectomized mice. In conclusion, our results indicated that Rg3 restores androgen deficiency-triggered xerostomia via AR-mediated AQP5 upregulation.

Odontoblasts are terminally differentiated cells that exhibit mechanosensitivity and mineralization capacity. Mechanosensitive ion channels such as Piezo1 are present in odontoblasts and are associated with their physiological functions via Ca²⁺ signaling. Both Ca²⁺ signals via Ca²⁺ influx from mechanosensitive ion channels and Ca²⁺ release from Ca²⁺ stores function as secondary messenger systems for various biological phenomena. The endoplasmic reticulum (ER) serves as an intracellular Ca²⁺ store that mobilizes intracellular Ca²⁺. Changes in Ca²⁺ concentration inside the ER are among the factors that cause ER stress. Perivascular cells are located around odontoblasts in the dental pulp. Although such formation indicates that perivascular cells interact with odontoblasts, their detailed profiles under developmental and pathological conditions remain unclear. In this study, we revealed that pericyte marker, neural/glial antigen 2 (NG2)-positive cells, in cell-rich zones (CZs) can differentiate into Piezo1-positive odontoblasts following genetic odontoblast depletion in mice, and modeled as odontoblast death after severe dentin injury and as reparative dentin formation. NG2-positive pericytes differentiated into odontoblasts faster than glial cells. To determine how NG2-positive cells differentiate into Piezo1-positive odontoblasts, we focused on the ER-stress sensor protein, activating transcription factor 6a (ATF6a). After genetic odontoblast depletion, NG2-positive cells regenerated in the odontoblast layer and were capable of acting as functional odontoblasts. In the presence of extracellular Ca²⁺, the application of a sarco/ER Ca²⁺-ATPase (SERCA) inhibitor, thapsigargin, known as an ER-stress inducer, increased the intracellular Ca²⁺ concentration in the odontoblast lineage cells (OLCs). The increase was significantly inhibited by the application of a pharmacologic Piezo1 inhibitor, indicating that ER stress by SERCA inhibition augmented Piezo1-induced responses in odontoblast progenitor cells. However, the physiological activation of G_q-coupled receptors by adenosine diphosphate did not induce Piezo1 activation. Gene silencing of ATF6a and/or NG2 impaired the mineralization of OLCs. Overall, ATF6a orchestrates the differentiation of NG2-positive pericytes into functional odontoblasts that act as sensory receptor cells and dentin-forming cells.

Porphyromonas gingivalis is one of the major pathogens of chronic periodontitis. P. gingivalis can cause systemic inflammation, amyloid β protein deposition, and hyperphosphorylation of tau protein, leading to Alzheimer's disease (AD)-like lesions. P. gingivalis oral infection causes gut microbiota alteration, gut barrier dysfunction, and intestinal immune response and inflammation. The microbiota-gut-brain axis has a potential role in the pathogenesis of AD. Whether P. gingivalis affects AD-like lesions via the gut-brain axis needs more study. In this study, orally administered P. gingivalis induced alveolar resorption, intestinal barrier impairment, and AD-like lesions. Oral infection with P. gingivalis induced oral and gut microflora dysbiosis, imbalance of the tryptophan metabolism pathway of gut microbiota, and elevated levels of 3-hydroxykynurenine in the sera and hippocampi. The key metabolite, 3-hydroxykynurenine, suppressed Bcl2 gene expression, leading to neuronal apoptosis and promoting AD-like lesions in vivo and in vitro. These findings suggest that P. gingivalis can induce AD pathogenesis through the gut-brain axis, providing new ideas for the prevention and treatment of AD.

Genetic dental disorders (GDDs) can occur either isolated or as part of syndromes. Clinically, deviations in tooth shape, size, or structure, as well as the absence of multiple teeth, lead to severe dysfunction and a reduced quality of life, requiring lifelong preventive, conservative, and prosthodontic dental care. The dental management of prevalent dental diseases, such as caries or periodontitis, has been based on decades of research, whereas scientific data on the dental management of GDDs are scarce. This lack of data is challenging for dental practitioners, who must primarily rely on empirical knowledge only. Therefore, a systematic literature search and review were conducted on the dental management of common GDDs, such as ectodermal dysplasia, amelogenesis imperfecta, dentinogenesis imperfecta, periodontitis as a manifestation of rare systemic diseases, and X-linked hypophosphatemia and hypophosphatasia. The review revealed that 468 of the 9,115 retrieved publications met the inclusion criteria, with most being case reports or case series, highlighting a lack of robust clinical trials. This critical review provides a brief summary of the genetic background, key clinical signs, and treatment options for these conditions. The dominance of case reports emphasizes the need for improved reporting standards and long-term follow-up to support comprehensive data synthesis and meta-analyses. In addition, the uneven global distribution of publications suggests disparities in access to advanced dental care for GDDs. Efforts to standardize reporting and improve treatment documentation globally are crucial to addressing these challenges. In this way, information on GDD management can be improved, and statistical analyses of the data can be performed.

It has been questioned whether Streptococcus mutans can still be considered the major etiological agent for caries. The main argument is that most evidence has been based on single-species identification. The composition of the oral microbiome was not analyzed. This systemic review aims to assess the prevalence and abundance of S. mutans in caries-active (CA) and caries-free (CF) subjects based on clinical studies in which the microbiome was investigated. Three databases (PubMed, Cochrane, Embase) were searched until May 22, 2023, for eligible publications that included CA and CF subjects and reported the detection of both S. mutans and the oral microbial community, using DNA-based methods. The clinical and microbial outcomes were summarized and further analyzed using a random-effects model. Of 22 eligible studies, 3 were excluded due to the high risk of bias. In the remaining 19 studies, 16 reported the prevalence of S. mutans, 11 reported its relative abundance, and 8 reported both parameters. The prevalence of S. mutans in CA was either similar to (n = 4) or higher than (n = 12) the CF group. The reported relative abundance in CA was higher than CF in all 11 studies, although the values varied from 0.001% to 5%. Meta-analysis confirmed the significance of these findings. The summary of microbial community data did not reveal other caries-associated bacterial genera/species than S. mutans. In conclusion, the collected evidence based on microbiome studies suggests a strong association between the prevalence and abundance of S. mutans and caries experience. While the cariogenic role of S. mutans in the oral ecosystem should be recognized, its actual function warrants further exploration.

High-quality prevalence and incidence studies of oral conditions are essential for estimation of disease burden and comparison of estimates among countries and over time, as well as for priority setting, resource allocation, and planning public health action. Existing systematic reviews of the epidemiology of untreated dental caries, severe periodontitis, and edentulism, carried out for the Global Burden of Disease study, showed inadequate and incomplete reporting of the measurement of oral conditions as well as a lack of consistency and comparability with other health conditions. These issues are more accentuated in studies from low- and middle-income countries. Studies must meet the highest standards so that these efforts do not waste resources. This report extends the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines to improve and standardize the reporting of descriptive oral epidemiologic studies of common oral conditions. The aim of the Guidelines for Reporting Oral Epidemiologic Studies to Inform Burden Estimation (GROESBE) is to promote transparency, clarity, and comparability of scientific reporting, specifically for prevalence and incidence studies of untreated caries, severe periodontitis, and edentulism. The GROESBE guidelines and checklist were developed following a structured and formal consultation process with a geographically diverse group of 23 individuals involved in the conduct and analysis of oral epidemiologic studies. GROESBE focuses on elements that are not included in STROBE, adding 14 specific recommendations to existing guidelines. They will facilitate reliable comparison of emerging prevalence and incidence data on untreated caries, severe periodontitis, and edentulism across settings worldwide and the synthesis of robust evidence to inform estimation of disease burden in future iterations of the Global Burden of Disease study.

Periodontal and peri-implant diseases are primarily biofilm-induced pathologies in susceptible hosts affecting the periodontium and dental implants. Differences in disease susceptibility, severity, and patterns of progression have been attributed to immune regulatory mechanisms such as epigenetics. DNA methylation is an essential epigenetic mechanism governing gene expression that plays pivotal roles in genomic imprinting, chromosomal stability, apoptosis, and aging. Clinical studies have explored DNA methylation inhibitors for cancer treatment and predictive methylation profiles for disease progression. In periodontal health, DNA methylation has emerged as critical, evidenced by clinical studies unraveling its complex interplay with inflammatory genes and its regulatory role in periodontitis contributing to disease severity. Human studies have shown that methylation enzymes associated with gene reactivation (e.g., ten-eleven translocation-2) are elevated in periodontitis compared with gingivitis. Dysregulation of these genes can lead to the production of inflammatory cytokines and an altered initial response to bacteria via the toll-like receptor signaling pathway in periodontal diseases. In addition, in peri-implant diseases, this dysregulation can result in altered DNA methylation levels and enzymatic activity influenced by the properties of the titanium surface. Beyond traditional perspectives, recent evidence highlights the involvement of RNA methylation (e.g., N6-methyladenosine [m6A], N6,2'-0-dimethyladenosine [m6Am]) in periodontitis and peri-implantitis lesions, playing vital roles in the innate immune response, production of inflammatory cytokines, and activation of dendritic cells. Both DNA and RNA methylation can influence the gene expression, virulence, and bacterial behavior of well-known periodontal pathogens such as Porphyromonas gingivalis. Alterations in bacterial methylation patterns result in changes in the metabolism, drug resistance, and gene expression related to survival in the host, thereby promoting tissue degradation and chronic inflammatory responses. In summary, the present state-of-the-art review navigates the evolving landscape of DNA and RNA methylation in periodontal and peri-implant diseases, integrating recent developments and mechanisms to reshape the understanding of epigenetic dynamics in oral health.

Circadian rhythm disruption is thought to be associated with periodontitis, and molecular clock genes play critical roles in regulating bone homeostasis. However, the specific contribution of molecular clock genes to alveolar bone resorption caused by periodontitis is poorly understood. In this study, we introduced a novel Periodontitis Circadian Rhythm Score (PeriCRS) model that was established through machine learning using periodontal transcriptomic data from periodontitis clinical cohorts in the Gene Expression Omnibus (GEO) database. This approach revealed the potential regulatory role of circadian rhythm disruption in periodontitis and identified key molecular clock genes associated with alveolar bone destruction. Moreover, we established an experimental periodontitis model with circadian rhythm disturbance via periodontal ligation in mice exposed to a 6-h advanced LD12:12 cycle every 2 d. Our bioinformatics analysis revealed that NR1D1, which encodes REV-ERBα, is a pivotal factor in the impact of circadian rhythm disruption on periodontitis in periodontal tissues. Next, we confirmed the abnormal expression of the molecular clock gene Rev-erbα in inflammatory periodontal tissue in mice and confirmed that circadian rhythm disruption altered REV-ERBα expression. Furthermore, the activation of REV-ERBα with the agonist SR9009 notably decreased RANKL-induced osteoclast differentiation and suppressed the expression of osteoclast-related factors. Subsequent in vivo experiments demonstrated that SR9009 mitigated alveolar bone loss caused by periodontitis. Mechanistically, we found that the IL-22-STAT3 pathway inhibited REV-ERBα expression and modulated RANKL-induced osteoclast differentiation in vitro. Our results elucidate the role of REV-ERBα in osteoclastogenesis and suggest a potential new therapeutic avenue for addressing alveolar bone resorption associated with periodontitis.

Recent years have seen significant positive changes and developments in oral health-related policy and data on oral health and oral health care in Canada. Simultaneously, on the international stage, the momentum for oral health and related research continues to build. These changes have led to an initiative to create Canada's first National Oral Health Research Strategy (NOHRS), which was recently published by the Canadian Institutes of Health Research-Institute of Musculoskeletal Health and Arthritis (Allison and Rock 2024). In this communication, we describe the process that was used to undertake this work. We present the resulting guiding principles, the research priority areas, and the framework that emerged, which included 6 strategic priorities grouped into 3 themes: (A) Leading Issues: (1) access to care, (2) inequities, identities, and oral health; (B) Emerging Methods: (3) artificial intelligence, (4) omics; and (C) Overarching Approaches: (5) environmental sustainability, (6) knowledge mobilization and implementation science. In addition, NOHRS includes a series of proposed goals and a timeline over the coming years. The point is to encourage a broad range of individuals and groups of people to engage with this high-level strategy and create plans to implement it. This strategy directly answers the call by the World Health Organization for countries to establish a national oral health research strategy (World Health Organization 2024). We have engaged in an extensive, broad consultative process, resulting in a Canadian NOHRS that is tailored to the needs of our community. Its aim is to galvanize our community into action to address the priorities we have identified. By engaging in this process, we build upon multiple oral health-related initiatives in Canada and on the international stage. We hope to inspire and facilitate similar, much-needed work elsewhere.

In population-based longitudinal studies, bias caused by nonresponse among eligible participants and attrition during follow-up thwarts conclusions. As this issue is not commonly addressed in dental studies, it is the aim of this study to examine the consequences of attrition with respect to tooth loss and mortality in a 10-y follow-up study. From the Study of Health in Pomerania (SHIP-0), a biological age (BA) score was constructed from 10 systemic biomarkers and related to one's actual chronological age (CA). The 3,417 dentate participants were stratified according to their BA-CA scores into tertiles: individuals with younger BA than their CA, those with concurrent BA and CA, and those with older BA than their CA. Baseline characteristics and propensity of leaving or remaining in the study were compared across these tertiles. We compared the characteristics within BA strata in the remainers of SHIP-2 (10-y follow-up) and their impact on tooth loss. Besides dropout by those who died, the attrition propensity of baseline study participants was dose dependent as related to BA-CA scores and socioeconomic factors. BA younger participants were underrepresented in dropouts but overrepresented in remaining follow-up participants. BA younger participants had a more favorable risk profile, better oral health, and a lower mortality rate than BA older participants. For the BA older participants, the opposite was observed. Remainers attaining the follow-up SHIP-2 were healthier and more health conscious. After 10 y, their tooth retention was still directed by BA constructed at baseline. The results support the assumption that individual risk profiles aggregated in BA constitute characteristic susceptibility patterns affecting perseverance or attrition in long-term follow-up studies. Attrition, which is common to follow-up studies, changes the study composition of participants depending on their BA and hence the transferability of results to the baseline population. The baseline BA gradient persists even after a long time.