Journal of Dental Research最新文献

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Enhancer Regulation of OSR2 in Mandibular Incisor Agenesis Susceptibility 增强子调控OSR2对下颌切牙发育易感性的影响
IF 7.6 1区 医学
Journal of Dental Research Pub Date : 2026-07-18 DOI: 10.1177/00220345261451773
L. Fan, X. Zhang, J. Mao, B. Vona, X. Xu, M. Du, L. Ma, Y. Pan
{"title":"Enhancer Regulation of OSR2 in Mandibular Incisor Agenesis Susceptibility","authors":"L. Fan, X. Zhang, J. Mao, B. Vona, X. Xu, M. Du, L. Ma, Y. Pan","doi":"10.1177/00220345261451773","DOIUrl":"https://doi.org/10.1177/00220345261451773","url":null,"abstract":"Mandibular incisors are the most frequently congenitally absent teeth in Asian populations, affecting mastication, speech, aesthetics, and oral and maxillofacial functions over the long term. However, the genetic etiology of mandibular incisor agenesis (MIA) remains obscure. In this study, we conducted the first genome-wide association study on MIA in a Chinese population and identified an enhancer variant, rs71514987, associated with an increased risk of MIA (odds ratio, 2.18; 95% CI, 1.83 to 2.58; <jats:italic toggle=\"yes\">P</jats:italic> = 3.62 × 10 <jats:sup>-19</jats:sup> ). Functional characterization indicated that the rs71514987 C allele reduced the binding affinity of GATA4 to the <jats:italic toggle=\"yes\">OSR2</jats:italic> promoter, leading to increased <jats:italic toggle=\"yes\">OSR2</jats:italic> expression via remote regulation. Notably, elevated <jats:italic toggle=\"yes\">OSR2</jats:italic> levels promoted cell proliferation but diminished cell differentiation, migration, and apoptosis capabilities in stem cells from human exfoliated deciduous teeth, as well as abnormal development of pharyngeal teeth in zebrafish models. Mechanistic experiments further revealed that OSR2 bound to the promoter region of <jats:italic toggle=\"yes\">CXCR4</jats:italic> , promoting its transcription level in the GPCR pathway, thereby influencing odontogenic differentiation during tooth development. Our findings provide novel insights into the molecular etiology of MIA.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"31 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148460103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
WNT Signaling Modifies Barrier Functions of Junctional and Pocket Epithelium WNT信号通路改变连接上皮和袋上皮的屏障功能
IF 7.6 1区 医学
Journal of Dental Research Pub Date : 2026-07-18 DOI: 10.1177/00220345261458716
F. Aellos, E. Chang, E. Jeong, B. Liu, X. Yuan, R. Nazari, F. Hermans, M.M. Torabi, P.C. Ochweri, P. Cuevas, S. Rao, K.A. Apaza Alccayhuaman, A. Sandoval, B.R. Coyac, I. Lambrichts, J.A. Helms
{"title":"WNT Signaling Modifies Barrier Functions of Junctional and Pocket Epithelium","authors":"F. Aellos, E. Chang, E. Jeong, B. Liu, X. Yuan, R. Nazari, F. Hermans, M.M. Torabi, P.C. Ochweri, P. Cuevas, S. Rao, K.A. Apaza Alccayhuaman, A. Sandoval, B.R. Coyac, I. Lambrichts, J.A. Helms","doi":"10.1177/00220345261458716","DOIUrl":"https://doi.org/10.1177/00220345261458716","url":null,"abstract":"The aims of this study were 1) to determine how ligature-induced periodontitis (LIP) disrupts barrier functions of the junctional epithelium (JE); 2) to determine, using a genetic approach, the necessity of Wnt signaling for JE barrier functions; and 3) to test, using a biochemical strategy, whether a WNT therapeutic is sufficient to improve barrier functions of a pocket epithelium. In a murine model of LIP, quantitative analyses performed at multiple time points assessed epithelial apoptosis; expression of attachment proteins laminin 5 and β4 integrin, inflammation, and bone resorption. <jats:italic toggle=\"yes\"> Axin2 <jats:sup>CreERT2/+</jats:sup> ; R26R <jats:sup>mTmG/+</jats:sup> </jats:italic> mice were used to evaluate how LIP impacted Wnt-responsive cells and their progeny, and <jats:italic toggle=\"yes\"> K14 <jats:sup>CreERT2/+</jats:sup> ;Wls <jats:sup>fl/fl</jats:sup> </jats:italic> mice were used to determine whether Wnt signaling was required for JE barrier functions. In some cases, LIP was followed by a recovery period to assess molecular changes in pocket epithelium, and in a subset of these mice, a liposomal formulation of human WNT3A protein (L-WNT3A) was tested for its effects on early repair dynamics in pocket epithelium. LIP triggered apoptosis, significantly reduced expression of laminin 5 and β4 integrin in the JE, and disrupted the Wnt-responsive compartment; these epithelial changes were accompanied by inflammation and alveolar bone resorption. Reepithelialization occurred even with a ligature present, but this pocket epithelium had compromised barrier functions. Wntless (Wls) deletion was sufficient to convert a JE into pocket epithelium, while topical L-WNT3A treatment was sufficient to increase hemidesmosomal protein expression in pocket epithelium and reduce inflammation at early time points. LIP destroys barrier functions and thus converts a JE into pocket epithelium. Deletion of epithelial <jats:italic toggle=\"yes\">Wls</jats:italic> demonstrates that this conversion is a Wnt-dependent event. L-WNT3A restores some early barrier features to pocket epithelium; future studies will focus on the durability of these effects.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"22 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148460104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epithelial Edar Is Responsible for Dental Anomalies in HED 上皮细胞Edar是导致HED牙齿异常的原因
IF 7.6 1区 医学
Journal of Dental Research Pub Date : 2026-07-18 DOI: 10.1177/00220345261453329
W.Y. Xu, F. Yang, X.R. Han, Y. Zhao, F. Wang, Q.G. Dai, Y.Q. Wu
{"title":"Epithelial Edar Is Responsible for Dental Anomalies in HED","authors":"W.Y. Xu, F. Yang, X.R. Han, Y. Zhao, F. Wang, Q.G. Dai, Y.Q. Wu","doi":"10.1177/00220345261453329","DOIUrl":"https://doi.org/10.1177/00220345261453329","url":null,"abstract":"Hypohidrotic ectodermal dysplasia (HED), primarily caused by mutations in <jats:italic toggle=\"yes\">EDA</jats:italic> and <jats:italic toggle=\"yes\">EDAR</jats:italic> , is characterized by tooth agenesis and other dental anomalies, including smaller teeth, conical or peg-shaped teeth, and taurodontism. However, the specific role of <jats:italic toggle=\"yes\">EDAR</jats:italic> in this process remains unclear, and suitable animal models for functional studies are lacking. In this study, we generated both global and epithelium-specific <jats:italic toggle=\"yes\">Edar</jats:italic> knockout mice, demonstrating that epithelial <jats:italic toggle=\"yes\">Edar</jats:italic> is essential for ectodermal organ development. Loss of <jats:italic toggle=\"yes\">Edar</jats:italic> in the epithelium led to multiple developmental dental anomalies, including third molar agenesis, reduced tooth size, fused roots, decreased cusp number, taurodontism-like molars, and enamel hypoplasia, which could mimic most of the phenotypes seen in global <jats:italic toggle=\"yes\">Edar</jats:italic> deletion and HED. Single-cell RNA sequencing further revealed that <jats:italic toggle=\"yes\">Edar</jats:italic> deletion alters the normal developmental progression of preameloblast lineage cells toward later ameloblast states. This alteration may underlie the enamel defects observed upon <jats:italic toggle=\"yes\">Edar</jats:italic> loss and is further supported by the finding that <jats:italic toggle=\"yes\">Edar</jats:italic> knockdown impaired mineralization of ameloblast lineage cells in vitro. Notably, <jats:italic toggle=\"yes\">Dlx3</jats:italic> was downregulated in ameloblasts at various stages in <jats:italic toggle=\"yes\">Edar</jats:italic> -deficient mice, and <jats:italic toggle=\"yes\">Dlx3</jats:italic> overexpression in <jats:italic toggle=\"yes\">Edar</jats:italic> -knockdown ameloblast lineage cells could rescue the mineralization function. Chromatin immunoprecipitation–quantitative polymerase chain reaction revealed that p65 binds to the <jats:italic toggle=\"yes\">Dlx3</jats:italic> promoter, linking <jats:italic toggle=\"yes\">Edar</jats:italic> to <jats:italic toggle=\"yes\">Dlx3</jats:italic> transcriptional activation via NF-κB signaling. Collectively, these findings reveal a critical role of epithelial EDAR in tooth development and, for the first time, provide evidence that its downregulated expression can lead to enamel formation defects, offering new insights into the pathogenic mechanisms of <jats:italic toggle=\"yes\">EDAR</jats:italic> -related HED.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"14 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Vape, the Mouth, and the Mycobiome: A Comparative Metagenomic Analysis 电子烟、口腔和真菌组:比较宏基因组分析
IF 7.6 1区 医学
Journal of Dental Research Pub Date : 2026-07-18 DOI: 10.1177/00220345261450182
R. Nikam, K. Kalani, M. Beverly, P.S. Kumar
{"title":"The Vape, the Mouth, and the Mycobiome: A Comparative Metagenomic Analysis","authors":"R. Nikam, K. Kalani, M. Beverly, P.S. Kumar","doi":"10.1177/00220345261450182","DOIUrl":"https://doi.org/10.1177/00220345261450182","url":null,"abstract":"Electronic nicotine delivery systems (ENDS), including e-cigarettes, are increasingly marketed as safer alternatives to combustible tobacco, yet their effects on oral health remain underexplored. Although the role of ENDS in creating dysbiotic oral bacterial communities is documented, effects on the oral mycobiome remain underexplored. This study compared the subgingival fungal communities of 123 periodontally and systemically healthy e-cigarette–only users, smokers, dual users, former smokers, and never-smokers using whole-genome shotgun sequencing for functional profiling. Taxonomic assignment using Kraken 2 and the PlusPF database identified 98 fungal taxa, and functional annotation with the Kyoto Encyclopedia of Genes and Genomes identified 2,960 fungal genes. Cross-domain bacterial–fungal interactions were interrogated using a correlation threshold of | <jats:italic toggle=\"yes\">r</jats:italic> | ≥ 0.7 and <jats:italic toggle=\"yes\">P</jats:italic> ≤ 0.001. E-cigarette users demonstrated a significantly higher α-diversity than smokers and never-smokers did ( <jats:italic toggle=\"yes\">P</jats:italic> &lt; 0.001; <jats:italic toggle=\"yes\">P</jats:italic> &lt; 0.005) and a mycobiome enriched with <jats:italic toggle=\"yes\">Candida albicans</jats:italic> , <jats:italic toggle=\"yes\">Aspergillus oryzae</jats:italic> , and <jats:italic toggle=\"yes\">Schizosaccharomyces pombe</jats:italic> . Functional profiling revealed enrichment of genes encoding or DNA repair, xenobiotic degradation, membrane transport, and stress response. The mycobiome of dual users and former smokers using e-cigarettes did not differ from that of e-cigarette users. Cross-kingdom networks identified 5- to 10-fold higher bacterial–fungal connectivity in e-cigarette users, with fungi capable of enhanced stress tolerance, DNA repair capacity, and metabolic adaptability acting as network anchors. Our data support an association between e-cigarette use and remodeling of the oral mycobiome and microbiome, driven by enhanced polymicrobial interactions and increased functional complexity, suggesting that assumptions regarding the biological neutrality of e-cigarette aerosols warrant further investigation.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"48 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Controllable Panoramic Radiograph Synthesis Using a Generative Model 基于生成模型的可控全景x光片合成
IF 7.6 1区 医学
Journal of Dental Research Pub Date : 2026-07-18 DOI: 10.1177/00220345261450592
Y.Y. Lin, W.T. Fu, X.L. Guo, W.H. Tang, J.X. Li, Y. Zhang, P.P. Chen, L.Q. Xu, L. He, Z.G. Zheng, C.K. Sun, Z.H. Liu, Q.K. Zhu, L.Y. Meng
{"title":"Controllable Panoramic Radiograph Synthesis Using a Generative Model","authors":"Y.Y. Lin, W.T. Fu, X.L. Guo, W.H. Tang, J.X. Li, Y. Zhang, P.P. Chen, L.Q. Xu, L. He, Z.G. Zheng, C.K. Sun, Z.H. Liu, Q.K. Zhu, L.Y. Meng","doi":"10.1177/00220345261450592","DOIUrl":"https://doi.org/10.1177/00220345261450592","url":null,"abstract":"Panoramic radiography (PR) is the one of the most widely prescribed diagnostic imaging modalities in dentistry. Achieving clinical-level automated interpretation of PR is critical for improving diagnostic efficiency, reducing radiologist workload, and ensuring interpretive consistency. Artificial intelligence (AI) has demonstrated significant utility and promise in PR interpretation, improving diagnostic efficiency, reducing radiologists’ workload, and enhancing interpretive consistency. However, developing AI-based PR interpretation methods remains hindered by persistent challenges of data scarcity, privacy constraints, and annotation imbalance. Facing these limitations, the aim of this study is to develop a disease-guided, anatomy-controllable generative model, named PRGen (for “panoramic radiograph generation”), designed to mitigate challenges related to data scarcity, privacy constraints, and annotation imbalance. PRGen is developed using 50,127 paired text–image samples and overcomes the uncontrollability of existing generative models, synthesizing both realistic PRs and paired masks from textual disease descriptions, enabling precise control of dental anatomy through simple or detailed sketches, and effectively mitigating barriers to large-scale, well-annotated dataset construction. We comprehensively evaluated the quality and clinical utility of PRGen-generated PRs across held-out internal test sets, publicly available datasets, and assessments by 10 radiologists. Incorporating PRGen-synthesized images into training led to a 47.59% improvement in Dice score for segmentation and a 11.53% increase in the area under the curve. Upon expert review, more than 82% of synthesized PRs were judged to faithfully reflect the described diseases while maintaining clinically realistic anatomical structures and radiographic appearances. External multicenter validation confirmed robust generalizability, with an average Dice improvement of 25.58% for segmentation and consistent gains in diagnostic tasks. Collectively, these results demonstrate that PRGen enables the generation of high-quality, mask-annotated PRs, thereby reducing the reliance on manual annotations and supporting more reliable and automated analysis of PRs, ultimately facilitating both model development and clinical translation.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"121 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Periodontal Measurement Accuracy and Reliability Using Intraoral Ultrasound 口腔内超声牙周测量的准确性和可靠性
IF 7.6 1区 医学
Journal of Dental Research Pub Date : 2026-07-18 DOI: 10.1177/00220345261446952
J. Wang, K.C.T. Nguyen, L. Graf-Alexiou, T.H. Hoang, L. Kumaralingam, M. Li, T.G. La, N.R. Kaipatur, E.H.M. Lou, P.W. Major, L.H. Le
{"title":"Periodontal Measurement Accuracy and Reliability Using Intraoral Ultrasound","authors":"J. Wang, K.C.T. Nguyen, L. Graf-Alexiou, T.H. Hoang, L. Kumaralingam, M. Li, T.G. La, N.R. Kaipatur, E.H.M. Lou, P.W. Major, L.H. Le","doi":"10.1177/00220345261446952","DOIUrl":"https://doi.org/10.1177/00220345261446952","url":null,"abstract":"Intraoral ultrasonography (iUS) has emerged as a noninvasive, radiation-free imaging modality capable of real-time visualization of both soft and hard tissues, yet its clinical accuracy and reliability remain incompletely characterized. This study aims to evaluate the accuracy and reliability of periodontal parameters measured on intraoral ultrasonograms. An in-house customized 20-MHz ultrasound imaging system with a rotational head was used to image the periodontium. Ex vivo accuracy was assessed in 58 teeth from 3 cadaver specimens with high-resolution micro–computed tomography ( <jats:italic toggle=\"yes\">µ</jats:italic> CT) as the gold standard. Two raters independently performed repeated measurements of alveolar bone level (ABL) and alveolar bone thickness (ABT) on 50 iUS images using a standardized anatomy-guided protocol. Intermethod agreement was quantified using intraclass correlation coefficients (ICCs), mean absolute differences (MADs), paired <jats:italic toggle=\"yes\">t</jats:italic> tests, and Bland–Altman analysis. In vivo clinical reliability was evaluated in 19 adolescents undergoing orthodontic treatment, with 3 raters measuring the ABL, ABT, attached gingival thickness, and free gingival thickness on 134 iUS images. Ex vivo analysis demonstrated excellent iUS accuracy and consistency for ABL (MAD 0.18–0.31 mm, ICCs 0.94–0.96) and excellent accuracy and good agreement for ABT (MAD 0.05 mm; ICCs 0.87). Paired <jats:italic toggle=\"yes\">t</jats:italic> tests revealed no significant differences between iUS and <jats:italic toggle=\"yes\">µ</jats:italic> CT measurements for either parameter (all <jats:italic toggle=\"yes\">P</jats:italic> &gt; 0.05). Bland–Altman analysis demonstrated excellent agreement with near-zero bias for both ABL and ABT, with narrow 95% limits of agreement across raters. In vivo measurements exhibited outstanding intrarater reliability (ICCs ≥ 0.84; MAD ≤ 0.10 mm) and good-to-excellent interrater reliability (ICCs ≥ 0.82; MAD ≤ 0.18 mm) for all parameters. The standardized, anatomy-guided protocol minimized operator dependency, enabling reproducible assessments across raters. These results demonstrate that iUS provides highly reproducible and reliable periodontal measurements in cadavers and healthy adolescents. Further studies in patients with moderate-to-severe periodontal disease are required to fully validate iUS for longitudinal monitoring.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"14 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148460102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RT2C: Predicting Time-to-New Caries with Structured Dental Data Using RNN RT2C:基于RNN的结构化牙齿数据预测新龋时间
IF 7.6 1区 医学
Journal of Dental Research Pub Date : 2026-07-18 DOI: 10.1177/00220345261462463
X. Liu, K.K. Kookal, R. Brandon, D.B. Rindal, J. Mullins, J.M. White, M.F. Walji, L. Rasmy
{"title":"RT2C: Predicting Time-to-New Caries with Structured Dental Data Using RNN","authors":"X. Liu, K.K. Kookal, R. Brandon, D.B. Rindal, J. Mullins, J.M. White, M.F. Walji, L. Rasmy","doi":"10.1177/00220345261462463","DOIUrl":"https://doi.org/10.1177/00220345261462463","url":null,"abstract":"Dental caries is a highly prevalent chronic condition requiring accurate tools to identify at-risk patients and guide preventive care. Most existing caries risk models provide only binary predictions and overlook time-to-event information. Considering that modern caries management relies on risk assessment during routine dental examinations, we developed RT2C, a survival model based on a recurrent neural network (RNN). This model supports caries risk management by assessing the likelihood (Caries Management by Risk Assessment [CAMBRA]) that a patient will be diagnosed with new caries by the next visit. It also estimates the time until this event occurs, using structured longitudinal dental data. Data were extracted from 4 dental organizations, comprising 466,782 patients and 1,062,553 examination visits (D0120, D0150, D0145) between 2019 and 2023. Structured electronic dental record (EDR) data included demographics, dental care history, clinical findings, and the CAMBRA–caries risk assessment (CRA). Patients were split into development (326,748 patients; 744,624 visits), validation (46,678; 106,616), and test (93,356; 211,313) sets, with similar event rates (~20%). The RT2C model used a bidirectional gated recurrent unit network to capture temporal dependencies across visits and estimate individualized survival probabilities. Model performance was compared against a Cox proportional hazards model and a random survival forest using the concordance index (C-index), integrated Brier score, and calibration analysis. Subgroup analyses evaluated generalizability across insurance types, age groups, racial groups, and CRA-based risk groups. The RT2C model achieved the highest concordance index on the held-out test set (0.883 ± 0.08), outperforming the CRA-only and traditional survival baselines. Performance remained consistent across demographic and clinical subgroups, demonstrating robustness and fairness across diverse populations. RT2C models visit-indexed risk trajectories and predicted new caries occurrence by the subsequent visit, aligning with the preventive framework of CAMBRA. By integrating longitudinal EDR data, it adds value to existing CRA tools and supports proactive, personalized caries management.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"24 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148461812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beyond Acidification: Microbial Lactate in the Oral Microbiome–Host Axis 超越酸化:口腔微生物群-宿主轴中的微生物乳酸
IF 7.6 1区 医学
Journal of Dental Research Pub Date : 2026-07-17 DOI: 10.1177/00220345261462879
N. Takahashi
{"title":"Beyond Acidification: Microbial Lactate in the Oral Microbiome–Host Axis","authors":"N. Takahashi","doi":"10.1177/00220345261462879","DOIUrl":"https://doi.org/10.1177/00220345261462879","url":null,"abstract":"Lactate, the major acidic end-product of carbohydrate metabolism in the oral microbiome, has long been recognized as a key driver of tooth demineralization by lowering the tooth surface pH below the critical threshold for enamel dissolution. Within the framework of the ecological plaque hypothesis, this frequent and prolonged acidification contributes to dysbiosis by favoring acidogenic and aciduric microorganisms. However, accumulating evidence indicates that microbiome-derived lactate plays broader roles in both microbial ecology and host physiology. This review synthesizes current knowledge on the multifaceted functions of lactate within the oral microbiome–host axis. Lactate produced by saccharolytic bacteria, mainly including <jats:italic toggle=\"yes\">Streptococcus</jats:italic> , <jats:italic toggle=\"yes\">Actinomyces</jats:italic> , and <jats:italic toggle=\"yes\">Lactobacillus</jats:italic> , as well as <jats:italic toggle=\"yes\">Rothia</jats:italic> and <jats:italic toggle=\"yes\">Gemella</jats:italic> , is extensively used by commensal taxa, including <jats:italic toggle=\"yes\">Veillonella</jats:italic> , <jats:italic toggle=\"yes\">Neisseria</jats:italic> , <jats:italic toggle=\"yes\">Rothia</jats:italic> , and <jats:italic toggle=\"yes\">Streptococcus oligofermentans</jats:italic> , and is primarily converted into acetate, propionate, and carbon dioxide. These cross-feeding interactions form integral metabolic networks within oral biofilms that are tightly coupled to the production of bioactive molecules, including nitrite, hydrogen peroxide, and hydrogen sulfide, contributing to microbial ecological homeostasis. Nitrite may further enter the systemic circulation and exert physiological effects, such as peripheral vasodilation via nitric oxide production through the nitrate–nitrite–nitric oxide pathway. Furthermore, in addition to directly damaging host cells at high concentrations, lactate may function as a signaling molecule through hydroxycarboxylic acid receptor 1 on host cells, potentially modulating cellular responses by regulating metabolic and signal transduction pathways. Lactate is also transported into cells via monocarboxylate transporters, where it serves as a metabolic substrate for redox regulation and induces epigenetic modifications through histone and non-histone protein lactylation, thereby affecting host cell functions. These multifaceted functions highlight lactate as a metabolic and signaling hub in the oral microbiome–host axis. The modulation of the lactate flux, rather than simply inhibiting microbial lactate production, may offer a new strategy for maintaining and promoting oral and systemic health.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"71 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sublingual Caruncle Taste Buds Drive Taste Perception and Salivary Reflexes 舌下结节味蕾驱动味觉知觉和唾液反射
IF 7.6 1区 医学
Journal of Dental Research Pub Date : 2026-07-17 DOI: 10.1177/00220345261451849
J. Liu, R. Xi, M. Han, X. Xu, M. Tizzano
{"title":"Sublingual Caruncle Taste Buds Drive Taste Perception and Salivary Reflexes","authors":"J. Liu, R. Xi, M. Han, X. Xu, M. Tizzano","doi":"10.1177/00220345261451849","DOIUrl":"https://doi.org/10.1177/00220345261451849","url":null,"abstract":"Taste buds (TBs) are the fundamental units of taste perception and are distributed throughout the oral cavity, including the tongue, soft palate, epiglottis, pharynx, and retromolar pad. Despite their widespread presence, a complete and systematic understanding of TB distribution and functional organization remains incomplete. In this study, we focus on a small population of TBs located in the mandibular sublingual caruncle of mice, adjacent to the openings of the Wharton’s ducts, a site previously noted in anatomical and physiological studies that has not been comprehensively characterized. TBs of the sublingual caruncle exhibit canonical morphology and cellular composition, comprising type I ( <jats:italic toggle=\"yes\">NTPDase2</jats:italic> +), type II ( <jats:italic toggle=\"yes\">Trpm5</jats:italic> +), and type III ( <jats:italic toggle=\"yes\">Car4</jats:italic> +) cells, as confirmed by transgenic reporter lines and immunofluorescence staining. Molecular analysis revealed the expression of key taste transduction components, including <jats:italic toggle=\"yes\">Gnat3</jats:italic> , <jats:italic toggle=\"yes\">Trpm5</jats:italic> , and <jats:italic toggle=\"yes\">Plcb2</jats:italic> , as well as 26 of 35 bitter taste receptors. Immunofluorescence confirmed TB innervation by <jats:italic toggle=\"yes\">βIII-tubulin</jats:italic> –positive nerve fibers, including <jats:italic toggle=\"yes\">P2X3</jats:italic> -positive sensory afferents, <jats:italic toggle=\"yes\">Synapsin-1</jats:italic> –positive presynaptic terminals, and <jats:italic toggle=\"yes\">CGRP</jats:italic> -positive peptidergic endings, indicating integration into the peripheral gustatory circuitry. Retrograde neuronal tracing (Dil/DiO) further demonstrated that nerve fibers associated with sublingual caruncle TBs project specifically to the geniculate but not the petrosal ganglion, supporting their attribution to the facial gustatory pathway. Functionally, localized sucrose stimulation of the sublingual caruncle elicited <jats:italic toggle=\"yes\">cFos</jats:italic> activation in the nucleus of the solitary tract, indicating central connectivity. Furthermore, tastants representing all 5 basic taste qualities (sweet, sour, bitter, umami, and salty) elicited measurable saliva secretion, with bitter-, sweet-, and umami-induced salivation reduced in transgenic mouse models with impaired gustatory function. Together, these findings establish the sublingual caruncle as a functional gustatory site involved in taste-evoked salivary reflexes, expanding current understanding of taste system organization and its coordination with salivary function.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"2 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148461805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reversing Enamel Mineralization Inhibition Using Amyloid-like Protein Film 淀粉样蛋白膜逆转牙釉质矿化抑制
IF 7.6 1区 医学
Journal of Dental Research Pub Date : 2026-07-17 DOI: 10.1177/00220345261461497
B. Hu, C. Li, X. Yang, Y. Pang, Y. Liu, J. Zhao, C. Fu, Y. Zhang, J. Wang, Z. Wang, S. Yang, K. Xuan, P. Yang
{"title":"Reversing Enamel Mineralization Inhibition Using Amyloid-like Protein Film","authors":"B. Hu, C. Li, X. Yang, Y. Pang, Y. Liu, J. Zhao, C. Fu, Y. Zhang, J. Wang, Z. Wang, S. Yang, K. Xuan, P. Yang","doi":"10.1177/00220345261461497","DOIUrl":"https://doi.org/10.1177/00220345261461497","url":null,"abstract":"Enamel remineralization holds considerable promise for dental caries, yet clinical translation remains hampered by the spontaneous deposition of acquired salivary pellicle (ASP), which passivates enamel surfaces and suppresses mineralization kinetics. Here, we present an ASP-repelling mineralization strategy based on a phase-transitioned bovine serum albumin (PTB) nanocoating fabricated via amyloid-like protein self-assembly. The PTB nanocoating confers robust antifouling properties that effectively inhibit ASP adsorption while simultaneously providing exceptional biomineralization activity. Under simulated physiological oral conditions, PTB drives heterogeneous nucleation and crystallization of calcium phosphate, generating a dense, well-integrated remineralized layer for enamel restoration. Both in vitro and in vivo evaluations demonstrate that ASP-coated enamel exhibits markedly attenuated remineralization capacity, whereas PTB treatment reverses this inhibition by efficiently repelling ASP and leveraging its abundant amino acid residues alongside amyloid-like architectures to direct mineral deposition. This work elucidates the interaction between ASP and remineralizing interfaces, providing a conceptually novel and clinically promising avenue to overcome remineralization barriers for caries prevention and enamel restoration.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"30 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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