Journal of dental research最新文献

{"title":"Advancing a Global Oral Health Research Agenda.","authors":"L D Rock, S M Balaji, H Benzian, L Cohen, E Collado-González, D S Cruz, R N D'Souza, A Echevarria-Goche, L Giner-Tarrida, E Figuero, M O Foláyan, C H Fox, J E Gallagher, A M Glenny, N S Jakubovics, D Kavanagh, M R Khami, P Leggett, M C Manzanares, H Mulhall, C Paganelli, S Pavitt, M A Peres, J A Platt, S Sharma, D E Slot, F Schwendicke, S Tubert-Jeannin, B Varenne, P C Yelick, P J Allison","doi":"10.1177/00220345261453872","DOIUrl":"10.1177/00220345261453872","url":null,"abstract":"<p><p>National oral health research strategies (NOHRSs) are increasingly recognized as critical mechanisms for aligning oral health research with public health needs, strengthening health systems, and advancing the World Health Organization's (WHO's) vision of \"oral health for all.\" They are also pivotal for accelerating global progress toward Strategic Objective 6 of the WHO Global Oral Health Action Plan 2023-2030, which calls for the development of public health-oriented national research agendas. While global momentum for NOHRS development is growing, countries remain at markedly different stages of readiness and implementation. To support coordinated international progress, a satellite workshop was convened at the International Association for Dental, Oral, and Craniofacial Research (IADR) General Session and Pan European (PER) Congress in Barcelona, Spain, in June 2025. The workshop brought together invited participants, policymakers, and researchers representing diverse geographic, economic, and governance contexts. Drawing on a preworkshop survey, invited workshop presentations, and structured breakout discussions, this article synthesizes key insights and lessons learned.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1105-1111"},"PeriodicalIF":5.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148261016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpretable Machine Learning for Population-Level Tooth Loss Prediction.","authors":"Q T Lam, F-Y Fan, Y-L Wang, C-Y Wu, Y-S Sun, T T T Vo, H Kuo, Q H Kha, M H N Le, G Vu, N Q K Le, I-T Lee","doi":"10.1177/00220345261464887","DOIUrl":"https://doi.org/10.1177/00220345261464887","url":null,"abstract":"<p><p>Machine learning can support population-level severe tooth loss (STL; ≥6 missing teeth) risk stratification; however, a lack of calibration under domain shift, limited interpretability of conventional black-box models, and inadequate handling of complex survey designs constrain responsible public health interpretation and implementation. We implemented and evaluated an interpretable, survey-weighted Multiple Imputation by Chained Equations-Explainable Boosting Machine (MICE-EBM) framework for population-level STL prediction incorporating sociobehavioral and systemic health determinants. Representative US adult datasets were analyzed, including Behavioral Risk Factor Surveillance System (BRFSS) 2022 for model derivation (<i>N</i> = 433,772), BRFSS 2024 for temporal validation (<i>N</i> = 448,213), and National Health and Nutrition Examination Survey (NHANES) 2015-2018 for cross-survey evaluation under outcome-definition and measurement shift (<i>N</i> = 10,775). Missing data were addressed using an antileakage HistGradientBoosting-driven pipeline to preserve multivariate epidemiological variance. The EBM demonstrated strong temporal stability on BRFSS 2024 (area under the receiver-operating characteristic curve [AUC]: 0.863; Brier: 0.085). For BRFSS 2022, model performance yielded an AUC of 0.865 and a Brier score of 0.086; a 100-replicate locked-imputed-set bootstrap confirmed robustness with an optimism-corrected AUC of 0.860 and a Brier score of 0.088. Direct transfer to NHANES yielded an AUC of 0.754 with poor raw calibration (Brier: 0.192), whereas predefined isotonic recalibration improved the holdout Brier score to 0.136. Compared with black-box stacked meta-ensemble (AUC: 0.780), the pre-recalibration EBM had lower NHANES discrimination (AUC: 0.754) but retained intrinsic glass-box interpretability. Overall, the MICE-EBM model may support population-level STL risk stratification for US survey-based cohorts with intrinsic transparency and calibrated same-survey performance. Moreover, this TRIPOD+AI-compliant framework may support population-level dental public health planning, although cross-survey or international application requires local validation and recalibration prior to implementation.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261464887"},"PeriodicalIF":5.9,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Hyperlipidemia on Osseointegration and Peri-implant Diseases.","authors":"R Mai, X Li, X Yang, O Hu, J Zhang, S W Cheung, Y Tang, S Feng, L Huang, J Wang, Y Wu, Y Man, L Xiang","doi":"10.1177/00220345261442179","DOIUrl":"10.1177/00220345261442179","url":null,"abstract":"<p><p>The long-term success of dental implants depends critically on osseointegration and peri-implant tissue health. While local factors have been extensively investigated, the influence of systemic metabolic disorders-particularly hyperlipidemia-on implant outcomes remains insufficiently understood. Hyperlipidemia is among the most common metabolic diseases globally and is increasingly recognized for its adverse effects on bone metabolism, immune response, and microcirculation. However, its role in osseointegration, which is responsible for peri-implant bone healing and the development of peri-implant diseases, is still controversial and lacks systematic evaluation. Based on our summary of the latest literature, the process of osseointegration can be summarized as angiogenesis-mediated 5-phase osseointegration. The 5 phases refer to 1) hydration/protein adsorption, 2) platelet-mediated fibrin clot formation, 3) immune cell adhesion, 4) osteogenic-bacterial competitive adhesion, and 5) angiogenesis-osteogenesis coupling. Angiogenesis-mediated 5-phase osseointegration facilitates a dynamic perspective for understanding the physiological processes involved in osseointegration. This review comprehensively summarizes clinical and experimental studies on the relationship between hyperlipidemia and osseointegration. The analysis focuses on peri-implant bone healing and peri-implant disease development from the perspective of angiogenesis-mediated 5-phase osseointegration. To our knowledge, this review creatively integrates both clinical and experimental evidence regarding the impact of hyperlipidemia on peri-implant bone healing and complications.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"972-981"},"PeriodicalIF":5.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The IADR Policy and Position Statements on Safety of Dental Amalgam.","authors":"K J Scholz, F Cieplik, G Schmalz, N Dame-Teixeira, H Priya, L M A Tenuta, M K S Charles-Ayinde, C H Fox","doi":"10.1177/00220345261443296","DOIUrl":"10.1177/00220345261443296","url":null,"abstract":"<p><p>Dental amalgam has served as a widely used restorative material in dentistry for over 150 years, demonstrating long-term clinical performance, cost-effectiveness, safety, and ease of placement, especially in situations where alternative restorative materials may be clinically less effective or economically less feasible. Composed of approximately 50% elemental mercury alloyed with silver, tin, copper, and other metals, current scientific evidence supports the safety of dental amalgam for the general population, excluding individuals with allergies to amalgam components or severe renal impairment. The International Association for Dental, Oral, and Craniofacial Research (IADR) affirms that mercury bound within the amalgam alloy poses a negligible health risk under normal conditions of use and endorses the continued availability of amalgam when its clinical, practical, or economic benefits are evident. Nonetheless, IADR acknowledges that dental amalgam use contributes to cumulative mercury exposure throughout its life cycle, including exploitation, manufacturing, clinical application, and disposal of residual material or when a removal of the restoration is clinically indicated. Aligned with the Minamata Convention on Mercury, IADR supports a responsible phase-down strategy, emphasizing the importance of enhanced, evidence-based dental caries prevention to reduce the overall need for restorative interventions. Concurrently, the advancement of biocompatible and environmentally sustainable restorative materials with demonstrated equivalent or superior long-term clinical longevity and cost-effectiveness is critical to facilitating the amalgam phase-down without compromising oral health of patients by inferior restorative outcomes. This policy statement reflects a balanced integration of current scientific knowledge, environmental stewardship, and patient-centered clinical decision-making.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"965-971"},"PeriodicalIF":5.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Pyroptosis in Oral and Maxillofacial Diseases.","authors":"L Tang, Y Wang, Z Yu, Y Chai, Y Chen, G Yang, T Huang","doi":"10.1177/00220345261443990","DOIUrl":"10.1177/00220345261443990","url":null,"abstract":"<p><p>The oral and maxillofacial region is a complex microenvironment continuously exposed to microbial challenge, mechanical stress, and oncogenic stimuli. Accumulating human evidence firmly implicates pyroptosis in the pathogenesis of major oral and maxillofacial diseases, with cleaved gasdermin D (GSDMD)/gasdermin E (GSDME) detected in clinical specimens of periodontitis, peri-implantitis, apical periodontitis, oral lichen planus, and oral submucous fibrosis. The central mechanism involves inflammasome assembly (eg, NLRP3), leading to caspase activation, gasdermin cleavage (eg, GSDMD, GSDME), and consequent pyroptotic cell lysis. Functional in vivo studies establish a direct causal link: genetic ablation of caspase-1 attenuates alveolar bone loss in murine periodontitis models, while pharmacologic inhibition of NLRP3 mitigates fibrosis and slows disease progression in rat models of oral submucous fibrosis by suppressing pyroptosis. In peri-implantitis, NLRP3 suppression inhibits macrophage pyroptosis and promotes osteogenesis. Similarly, the activation of GSDMD and GSDME is shown to trigger pyroptosis and exacerbate pulpal and periapical inflammation in apical periodontitis models. Conversely, in oral squamous cell carcinoma, pyroptosis induction potently stimulates anti-tumor immunity. This context-dependent duality of pyroptosis provides the rationale for precision medicine. Emerging strategies reflecting this approach include cell-based therapies using dental pulp stem cells to alleviate pyroptosis and promote nerve regeneration in macaque models as well as advanced nanomaterials such as angiopoietin-coupled carbon nanotubes that modulate pyroptosis-related pathways to enhance bone regeneration in rabbits. Collectively, these insights position the precise modulation of pyroptosis as a new frontier in the management of oral and maxillofacial diseases.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"982-993"},"PeriodicalIF":5.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP/TAZ Drive Oral Leukoplakia Progression and Confer Ferroptosis Vulnerability.","authors":"D Yang, L Zhang, T Zhou, Q Yuan, J Zhang, X Xia, H Dan, X Feng","doi":"10.1177/00220345261451778","DOIUrl":"https://doi.org/10.1177/00220345261451778","url":null,"abstract":"<p><p>Oral leukoplakia (OLK), the most common potentially malignant oral disorder, poses a persistent clinical challenge due to high recurrence and malignant transformation rates, with no curative treatment currently available. Conventional interventions, including medications, surgery, laser, and photodynamic therapy, have shown limited success in cancerization prevention, largely because the abnormal events underlying the development and progression of OLK remain poorly defined. Here, through single-cell RNA sequencing profiles, we identified an OLK-specific cell population characterized by YAP/TAZ overactivation, which was strongly associated with disrupted epithelial homeostasis. Transgenic mouse models confirmed the essential role of YAP/TAZ activation in conferring the malignant phenotype of OLK and driving its progression toward transformation. Interestingly, although YAP/TAZ are technically and strategically considered undruggable, we uncovered a ferroptosis vulnerability in OLK malignant cells mediated by the YAP/TAZ-TEAD-TXNRD1 axis. Notably, we demonstrate that combining sulfasalazine and docosahexaenoic acid, 2 clinically available agents, effectively induces ferroptosis and attenuates OLK progression. These findings establish a mechanistic link between YAP/TAZ activation and OLK progression, specifically revealing the dual roles of YAP/TAZ in maintaining malignant properties while conferring ferroptosis vulnerability. This duality highlights ferroptosis induction as a promising therapeutic strategy for indirectly targeting YAP/TAZ. Moreover, the drug-repurposing approach provides a practical and translationally relevant avenue to improve OLK management and reduce the risk of malignant transformation.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261451778"},"PeriodicalIF":5.9,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148260791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiancestral GWAS of Dental Malocclusion Identifies Multiple Risk Loci.","authors":"A Alade, J M Maurer, J Anderton, M-K Lee, K Almpani, S Goovaerts, P Claes, A Butali, A Adeyemo, S Levy, J K Hartsfield, L A Morford, T Peter, S Miller, D W McNeil, J R Shaffer, B Foxman, S M Weinberg, L M Moreno Uribe, M L Marazita, J S Lee","doi":"10.1177/00220345261442129","DOIUrl":"https://doi.org/10.1177/00220345261442129","url":null,"abstract":"<p><p>Malocclusion is a common oral health problem with a strong hereditary component. Previous genetic studies were limited by small sample sizes and low genomic coverage. To address these limitations, we conducted a genome-wide association study (GWAS) using array-based genotype data in 5 large, multiancestral cohorts. The study included 3,405 participants from the United States and its territories, the Philippines, Colombia, and Nigeria. Class II malocclusion was defined as an Angle's class II molar relationship with an overjet >3.5 mm, class III malocclusion as an Angle's class III molar relationship with a negative overjet, and class I malocclusion (controls) as an Angle's class I molar relationship with an overjet of 0 to 3.5 mm. In the vertical plane, an anterior open bite of any magnitude was classified as \"open bite,\" while an overbite >3.5 mm was classified as \"deep bite,\" with controls having an overbite of 0 to 3.5 mm. Multiplanar malocclusion included cases with both sagittal and vertical discrepancies, with controls having an Angle's class I molar relationship, an overjet of 0 to 3.5 mm, and an overbite of 0 to 3.5 mm. GWAS for each phenotype was conducted within individual cohorts before meta-analysis. We identified genome-wide significant associations (<i>P</i> ≤ 5E-08) at 11q22.3 (rs372564249, odds ratio [OR] = 3.12) and 3p24.3 (rs13060317, OR = 2.4) for class II and multiplanar malocclusion, respectively. Additionally, we observed a near-significant signal at 12q15 (rs1261646, OR = 1.9, <i>P</i> = 6.2 × 10^-8) for class II malocclusion and a suggestive association at 1p21.3 (rs7541224, OR = 2.0, <i>P</i> = 1.7 × 10^-7) for class III malocclusion. The 11q22.3 and 3p24.3 loci were QTLs for the <i>PDGFD</i> and <i>SGO1-AS1</i> genes, and transcriptomic data showed consistent expression of these genes during facial development. These findings provide valuable insights into malocclusion etiology and lay the groundwork for genetic risk score development.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261442129"},"PeriodicalIF":5.9,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148260992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HED-Derived iPSCs Reveal Neurofunctional Defects in Ectodermal Dysplasia.","authors":"L Peng, X Song, Y Lin, X Tao, T Huan, Y Song, M He, Z Bian, W Yin","doi":"10.1177/00220345261450873","DOIUrl":"https://doi.org/10.1177/00220345261450873","url":null,"abstract":"<p><p>Ectodermal dysplasia (ED) is characterized by sparse hair, reduced sweat gland secretion, and congenital absence of teeth. While genes such as <i>EDA</i> and <i>EDAR</i> have been identified as causative factors of ED, the underlying mechanisms remain unknown, and corresponding treatments are not available. Here, we report a pedigree with hypohidrotic ectodermal dysplasia (HED), the most common subtype of ED, caused by a mutation in the <i>KDF1</i> gene. To investigate disease mechanisms, we generated induced pluripotent stem cells (iPSCs) of family members. Upon differentiation into embryoid bodies (EBs), the <i>KDF1</i> mutation severely impaired EB size and morphology. The single-cell RNA sequencing further demonstrated that iPSCs from both HED patients showed a specific shortage of several cell populations, whose biological characteristics were closely related to synapse structure and signaling. Initially, iPSCs were differentiated into neurons to analyze their functional changes. Concurrently, patient-derived iPSCs were differentiated into epidermal progenitor cells, and the effect of the N-methyl-D-aspartate receptor antagonist MK-801 during this process was investigated. We found that the overexpression of excitatory neurotransmitters might disrupt ectodermal development. These deficits were partially rescued after CRISPR-mediated correction of the <i>KDF1</i> mutation. Our work suggests that impaired synaptic structure and signaling impede ectodermal organogenesis in HED.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261450873"},"PeriodicalIF":5.9,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148213760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoring Cellular Homeostasis as a Therapeutic Strategy for Periodontitis.","authors":"H Jang, J Im, D-S Lee, D H Park, C Son, S H Ki, S Park, S M Roh, J-S Seo, O-J Park, J M Park, S Jang, J-C Park, S H Han","doi":"10.1177/00220345261450582","DOIUrl":"https://doi.org/10.1177/00220345261450582","url":null,"abstract":"<p><p>Periodontitis is a chronic inflammatory disease characterized by persistent inflammation, redox imbalance, and mitochondrial dysfunction, leading to progressive impairment of periodontal cellular function and tissue integrity. Current periodontal therapies primarily focus on controlling inflammation and promoting tissue regeneration. However, these approaches do not adequately restore the function of resident cells compromised by an inflammatory microenvironment. Restoration of cellular homeostasis prior to inducing regeneration may enhance treatment outcomes for effective periodontal repair. This study aimed to investigate the role of CPNE7 in periodontal homeostasis and to evaluate whether selcopintide (SCPT), a CPNE7-derived peptide, restores cellular function under inflammatory periodontal conditions and exerts therapeutic effects in a mouse ligature-induced periodontitis model. In aged periodontal tissues, CPNE7 expression was reduced, accompanied by increased oxidative stress and decreased Nrf2 expression. <i>Cpne7</i> knockout mice also exhibited periodontal structural abnormalities and showed aggravated alveolar bone loss and inflammatory responses following periodontitis induction. SCPT reduced excessive reactive oxygen species accumulation induced by inflammatory stimuli and restored redox balance, thereby supporting cellular homeostasis. In addition, SCPT improved mitochondrial function under inflammatory conditions, as evidenced by restored mitochondrial morphology and bioenergetic function, while attenuating inflammatory signaling and apoptosis. These protective effects were associated with activation of the Nrf2 antioxidant pathway. Importantly, topical administration of SCPT significantly attenuated periodontal destruction and alveolar bone loss in the ligature-induced periodontitis model, demonstrating its therapeutic efficacy <i>in vivo</i>. Collectively, these findings indicate that CPNE7 is an important contributor to periodontal tissue homeostasis and that SCPT restores redox balance, mitochondrial function, and inflammatory stability, highlighting CPNE7-derived peptides as a promising therapeutic strategy for periodontitis.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261450582"},"PeriodicalIF":5.9,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148213768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitrate-Sialin Promotes Dentin Regeneration via Mitochondrial Rewiring.","authors":"Z Cao, S Kong, O Jiang, J Wang, S Wang, X Li","doi":"10.1177/00220345261435516","DOIUrl":"https://doi.org/10.1177/00220345261435516","url":null,"abstract":"<p><p>The regenerative capacity of dental pulp declines as dental pulp stem cells (DPSCs) enter senescence, compromising pulp-dentin homeostasis, and actionable strategies to restore odontogenesis remain limited. Here, we identify that nitrate acts as a Sialin (<i>SLC17A5</i>)-dependent metabolic cue that promotes dentin regeneration by rewiring mitochondrial metabolism. Across 3 senescence models (natural aging, hydrogen peroxide, and etoposide), nitrate consistently reduced senescence features and restored odontogenic capacity. Silencing Sialin abolished these benefits, establishing pathway necessity. Untargeted metabolomics with pathway enrichment revealed activation of the tricarboxylic acid and pyruvate pathways, accompanied by higher adenosine triphosphate, an increased nicotinamide adenine dinucleotide redox ratio, improved mitochondrial respiratory performance, and lowered mitochondrial reactive oxygen species; these gains were blunted by Sialin loss. Pharmacologic perturbations linked metabolism to phenotype, as electron-transport inhibition negated nitrate's effects, whereas metabolic modulation partially restored antisenescence and pro-odontogenic outcomes. In a mouse pulp exposure model, local nitrate accelerated dentin bridge formation and tissue repair, but these effects were lost in mesenchymal Sialin conditional-knockout mice. Together, these findings establish a nitrate-Sialin-mitochondria axis that rejuvenates DPSCs, drives dentin regeneration, and restores pulp-dentin homeostasis, while supporting a practical local delivery approach with translational potential for vital pulp therapy.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261435516"},"PeriodicalIF":5.9,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148045174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}