{"title":"<i>Dmp1</i> Knock-in Mice Faithfully Report and Manipulate <i>Dmp1</i>-Expressing Cells.","authors":"T H Wang, M Yang, Y Liu, Y Jin, Y J Hu, Y Yang","doi":"10.1177/00220345261478577","DOIUrl":"https://doi.org/10.1177/00220345261478577","url":null,"abstract":"<p><p>Dentin, the primary structural component of teeth, is a mineralized tissue formed by odontoblasts, which strongly express the <i>Dmp1</i> gene. <i>Dmp1</i> is also expressed in osteocytes, making it a valuable marker for studying bone biology and diseases. Transgenic mouse lines expressing <i>Cre</i>, <i>CreER</i>, or fluorescent reporters such as <i>GFP</i> under the control of 8-kb or 10-kb <i>Dmp1</i> promoters have been widely used to investigate gene functions in odontoblasts and osteocytes. However, the transgenic models exhibit ectopic expression, and reporter signals are often reduced in mature odontoblasts, limiting their utility for lineage tracing and studies of terminal differentiation. To address these limitations, we generated 2 novel knock-in mouse lines, <i>Dmp1</i><sup>CreERT2</sup> and <i>Dmp1</i><sup>ZsGreen</sup>, using CRISPR-Cas9-mediated genome editing. In both models, an internal ribosome entry site (<i>IRES</i>)-<i>CreERT2</i> or <i>IRES-ZsGreen</i> cassette was inserted into the 3' untranslated region (UTR) of the endogenous <i>Dmp1</i> locus. This design preserves normal <i>Dmp1</i> expression while permitting robust, <i>Dmp1</i>-specific expression of <i>CreERT2</i> or <i>ZsGreen</i> in odontoblasts and cementoblast/cementocytes. By maintaining endogenous regulatory control, these knock-in lines eliminate the ectopic transgene expression commonly observed in transgenic mice generated by injecting the promoter-driven constructs. The <i>Dmp1</i><sup>ZsGreen</sup> line enables direct visualization of <i>Dmp1</i>-expressing odontoblasts and cementoblasts/cementocytes, while the <i>Dmp1</i><sup>CreERT2</sup> line allows inducible genetic manipulation in these cells in vivo. Together, these models provide faithful tools for investigating the cellular and molecular mechanisms regulating dentinogenesis and osteocyte biology, as well as for studying dental and alveolar bone tissues, with potential applications in craniofacial biology.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261478577"},"PeriodicalIF":5.9,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043065","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":"Divergent Utilization of Health Care Following Traumatic Life Events.","authors":"N Z Bashir, D Gonzalez-Padilla, A Wood, S Burgess","doi":"10.1177/00220345261475568","DOIUrl":"https://doi.org/10.1177/00220345261475568","url":null,"abstract":"<p><p>Traumatic life events may shape how individuals utilize health care, yet their impact on medical and dental service utilization is underexplored. This study investigates how such events influence subsequent health care use. We analyzed data from the Mexican Health and Aging Study, the first longitudinal cohort in Mexico of middle-aged and older adults. The analytic sample comprised 17,424 unique individuals across 39,875 total observations. Three traumatic events were examined in relation to their effects on medical and dental service use: (1) experience of a natural disaster, (2) experience of the death of a child, and (3) experience of a crime or accident. We combined propensity score weighting with multivariable mixed-effects logistic regression to account for both confounding and correlation arising from repeated measures. We estimated the effect of exposure to each traumatic event by parametric g-computation, calculating risk differences with 95% confidence intervals (CIs). Exposure to a natural disaster increased medical service use by 4.2% (95% CI, 2.2 to 6.2) while reducing utilization of dental care by 4.8% (95% CI, -7.0 to -2.5). The death of a child increased medical service use by 4.9% (95% CI, 2.7 to 7.2) while reducing utilization of dental care by 6.0% (95% CI, -8.6 to -3.4). Crime or accidents increased utilization of medical services by 12.7% (95% CI, 11.1 to 14.2) while having no clear effect on utilization of dental care. Traumatic events have substantial and differential impacts on health care utilization. In particular, among middle-aged and older adults in Mexico, natural disasters and the death of a child have divergent effects on the utilization of medical versus dental care, while crime and accidents only affect medical care. Future research into this underdeveloped area may help to develop a more precise understanding of the underlying mechanisms.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261475568"},"PeriodicalIF":5.9,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893198","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":"Letter to the Editor, \"Estimating the Individualized Effect of Tooth Extraction before Radiotherapy on Osteoradionecrosis Using Causal Machine Learning\".","authors":"Y M Zhou, X Meng","doi":"10.1177/00220345261449697","DOIUrl":"10.1177/00220345261449697","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1369"},"PeriodicalIF":5.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148213834","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}
M Moharrami, E Watson, S Singhal, S H Huang, C Yao, A Hosni, C Quinonez, M Glogauer
{"title":"Response to Letter to Editor: \"Estimating the Individualized Effect of Tooth Extraction before Radiotherapy on Osteoradionecrosis Using Causal Machine Learning\".","authors":"M Moharrami, E Watson, S Singhal, S H Huang, C Yao, A Hosni, C Quinonez, M Glogauer","doi":"10.1177/00220345261455850","DOIUrl":"10.1177/00220345261455850","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1370"},"PeriodicalIF":5.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378906","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}
W Al-Omairi, A Altaie, D J Wood, A Werner, M J German
{"title":"Fluoride-Releasing Fillers Modulate the Response of Fibroblasts to Dental Composites.","authors":"W Al-Omairi, A Altaie, D J Wood, A Werner, M J German","doi":"10.1177/00220345261460387","DOIUrl":"https://doi.org/10.1177/00220345261460387","url":null,"abstract":"<p><p>To reduce secondary caries-related restoration failure, ion-releasing fillers are being incorporated into resin-based composites (RBCs). However, a comprehensive investigation into the cytocompatibility of these materials, particularly concerning transcriptomic responses to monomer and ion release, has yet to be conducted. This study investigated model RBCs (80:20 UDMA:HEMA matrix, 62 vol% filler), including a fluorapatite (FA) containing composite (FA+, 9 vol%), to assess the effect of fluoride ion-releasing filler content on degree of conversion (DC%) and monomer release. Apparent water sorption and fluoride release were evaluated after 28 d of storage in artificial saliva (pH 7 and pH 4) and distilled deionized water. Cytocompatibility was assessed using an XTT assay on human gingival fibroblasts (HGFs), and the expression of genes encoding DNA-repair and stress-response markers following composite exposure was analyzed by quantitative reverse transcription polymerase chain reaction (RT-qPCR). RNA sequencing (RNA-seq) identified differentially expressed genes in response to FA+ and fluorapatite-free RBCs (FA-). Unfilled specimens exhibited lower DC% and higher monomer release compared to the RBCs. FA+ specimens had the highest apparent water sorption, particularly after pH 7 artificial saliva storage. Fluoride release was most significant in acidic environments. UDMA reduced HGF viability compared to HEMA at all concentrations up to 5 mM, but the polymerized RBCs caused no reduction compared to control HGFs. However, expression analysis by RT-qPCR of DNA-repair and stress-response markers following composite exposure revealed that UDMA reduced repair gene expression, whereas HEMA stimulated it. RNA-seq analysis revealed significant changes in gene expression profiles upon composite exposure, with enriched pathways related to ferroptosis and protein digestion. These findings highlight, for the first time, the potential for significant cellular responses even with limited composite component release from ion-releasing RBCs, underscoring the need for further research into the long-term biocompatibility of these materials.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261460387"},"PeriodicalIF":5.9,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148709218","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":"Vascular Patterning Shapes Intramembranous Ossification via the HIF1α-VEGF Axis.","authors":"S Dash, J R Rettig, M Gogol, P A Trainor","doi":"10.1177/00220345261463156","DOIUrl":"10.1177/00220345261463156","url":null,"abstract":"<p><p>Organs and tissues develop in close association with the vasculature, which transports blood and nutrients and helps to remove waste. The vasculature is composed primarily of endothelial cells, which provide structure, form barriers, and are a source of developmental signals. We recently found that Mediator, a multiprotein complex that regulates transcription, was essential for proper vascular development. Here, we investigated the specific role of the Mediator tail subunit Med23 in endothelial cells. Endothelial cell-specific knockout of <i>Med23</i> in mouse embryos using <i>Tek-Cre</i> resulted in vascular anomalies, including edema, hemorrhage, and mispatterned vasculature, alongside craniofacial defects such as micrognathia and cleft palate. Spatial transcriptomics revealed the downregulated expression of key vascular and osteogenic genes in <i>Med23</i> mutants, including <i>Vegfr1</i> and <i>Col1a1</i>, with altered signaling dynamics between endothelial and osteoblast populations. Elevated hypoxia-inducible factor 1-alpha (HIF1α) expression and reduced vascular endothelial growth factor (VEGF) signaling were observed in <i>Med23</i> mutants, suggesting a hypoxia-driven suppression of neural crest cell-derived osteoblast maturation. Consistent with this model, the pharmacologic inhibition of HIF1α, combined with VEGFA supplementation, rescued craniofacial ossification and extended embryonic viability. These findings reveal a critical role for Med23 in coordinating vascular patterning and intramembranous ossification and highlight distinct hypoxic and angiogenic requirements in craniofacial dermal bone versus axial and appendicular endochondral bone development. Thus, the cranial vasculature, and more specifically endothelial cells, plays an instructive role in neural crest cell and osteogenic differentiation during cranioskeletal development.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261463156"},"PeriodicalIF":5.9,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671735","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":"Proteomics of Cervical Mineralized Diaphragm in Molar Root-Incisor Malformation.","authors":"O H Nam, J R Ye, S W Kang, H-K Hyun","doi":"10.1177/00220345261467270","DOIUrl":"https://doi.org/10.1177/00220345261467270","url":null,"abstract":"<p><p>Molar root-incisor malformation (MRIM) is characterized by abnormalities in the root and pulpal floor, which may lead to dental complications. However, research on MRIM remains limited and is largely confined to case-based observations. Therefore, this study aimed to characterize the morphology and proteomic profile of the cervical mineralized diaphragm (CMD) in MRIM. Extracted MRIM-affected teeth (<i>n</i> = 11) from 6 patients and extracted third molars as controls (<i>n</i> = 11) were collected. Two MRIM-affected teeth and two control teeth were subjected to micro-computed tomography and scanning electron microscopy. CMD tissues adjacent to the pulpal floor and control pulpal-floor dentin were harvested for protein extraction and analyzed by liquid chromatography-tandem mass spectrometry. Label-free quantification and bioinformatics analyses (gene set enrichment and protein-protein interaction network analysis) were performed, and proteins with >2-fold change were considered differentially expressed. Micro-computed tomography demonstrated a highly radiopaque CMD at the pulpal floor that occluded pulp-root canal communication, with a radiodensity between that of the enamel and dentin and a dense/porous internal architecture. Scanning electron microscopy revealed columnar and crystal-like structures. Proteomic profiles differed between MRIM and controls, with reduced epithelial-mesenchymal transition signaling in MRIM (normalized enrichment score = 1.47, false discovery rate = 0.116; control vs. MRIM). A total of 116 proteins showed >2-fold change (62 upregulated and 54 downregulated). Upregulated proteins included keratinization-associated proteins (KRT75, KRT82, EVPL, and KRT6B) with enrichment of keratinization- and epidermis-related terms, whereas downregulated proteins included SPP1, AMBN, and ECM1, which were associated with biomineral tissue development. Within the limits of this study, the CMD in MRIM exhibits a distinctive mineralized microarchitecture and a proteomic signature implicating altered epithelial-associated and extracellular matrix/mineralization processes. These findings provide candidate targets for tissue-level validation and mechanistic studies of MRIM.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261467270"},"PeriodicalIF":5.9,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665058","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}
S Weng, Z Mao, I Topolniak, A A Diken Türksayar, J Yassine, F Beuer, F Schmidt
{"title":"Printing Parameters and Surface Treatments on Color and Translucency Stability.","authors":"S Weng, Z Mao, I Topolniak, A A Diken Türksayar, J Yassine, F Beuer, F Schmidt","doi":"10.1177/00220345261466570","DOIUrl":"https://doi.org/10.1177/00220345261466570","url":null,"abstract":"<p><p>Additive manufacturing (AM) has expanded in dentistry, yet the color and translucency stability of 3-dimensional-printed resin-based materials remain insufficiently understood. This study investigated the main and interaction effects of printing orientation, specimen thickness, and surface treatments on the color and translucency stability of a 3-dimensional printed resin-ceramic hybrid material. Ninety AM specimens were fabricated using a factorial design combining 3 printing orientations, 3 specimen thicknesses, and 2 surface treatments (3 × 3 × 2, <i>n</i> = 5 per condition) and compared with 30 subtractively manufactured control specimens (Vita Enamic). Aging was simulated by thermocycling (5000 cycles, 5-55 °C). Color coordinates were measured via the Commission Internationale de l'Éclairage L*a*b* color system, and color change and translucency change were calculated. Degree of conversion, water sorption, and surface roughness were also evaluated. Printing orientation and specimen thickness significantly affected color change and translucency change (<i>P</i> < 0.05), with the 90° orientation showing lower changes than 0° and 45°. Surface treatment had a limited influence on color and translucency stability, although glazing resulted in higher water sorption as compared with polishing (<i>P</i> < 0.05). No significant effects of printing orientation were observed for degree of conversion or surface roughness, whereas surface treatment significantly influenced surface roughness (<i>P</i> < 0.05). Despite these variations, all groups remained within clinically acceptable thresholds for color and translucency changes. Overall, the findings suggest that AM resin-ceramic restorations have potential for use in definitive restorations. Optimizing printing orientation and material thickness may enhance the color and translucency stability of AM resin-ceramic restorations, supporting their clinical applicability.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261466570"},"PeriodicalIF":5.9,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665083","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":"Extracellular Vesicles in Regenerative Dentistry.","authors":"P Ahmad, N E Estrin, R J Miron","doi":"10.1177/00220345261448514","DOIUrl":"10.1177/00220345261448514","url":null,"abstract":"<p><p>The regeneration of orodental and craniofacial tissues remains a primary clinical challenge owing to the requirement of harmonized integration of hard-soft tissues, immune modulation, neurogenesis, angiogenesis, and osteogenesis. Extracellular vesicles (EVs) are nanoparticles containing RNAs, metabolites, lipids, and proteins that have surfaced as vital paracrine regulators able to coordinate these intricate mechanisms without the intrinsic risks associated with cell transplantation. This review synthesizes extensive in vivo evidence and evolving clinical findings highlighting that EVs from immune cells, mesenchymal stem cells, dental stem cells, and engineered origins regulate periodontal and dental pulp regeneration, peri-implant osseointegration, temporomandibular joint disorders, root resorption, orthodontic tooth movement, and craniomaxillofacial bone repair. EVs function as context-based biological regulators: regenerative EVs enhance M2 (anti-inflammatory) macrophage polarization, neurogenesis, angiogenesis, and odonto-osteogenesis, while EVs from pathogenic, mechanically stressed, or inflamed cells can initiate inflammation, osteoclastogenesis, and tissue damage. EV long noncoding RNAs and microRNAs play a critical part in dictating reparative versus destructive outcomes by regulating the TGF-β/SMAD, PI3K/protein kinase B, NF-κB, and immune-metabolic cascades. Biomaterial-based delivery platforms and engineered EVs, such as surface-modified dental implants, scaffolds, and hydrogels, consistently improved local retention, efficacy, and multi-tissue repair. Crucially, human studies indicate clinically significant enhancements in periodontal and alveolar bone regeneration, emphasizing their translational promise. Nonetheless, clinical implementation is restricted by heterogeneity in EV origins, cargo variability, manufacturing methods, dosage, and delivery approaches, together with an incomplete comprehension of how to predict their bioactivity. Future advances will mandate Minimal Information for Studies of Extracellular Vesicles (MISEV)-guided optimization, functional release criteria, localized delivery systems, potency-driven classification, and scalable Good Manufacturing Practices production. Overall, current evidence positions EVs as cell-free, adaptable mediators with transformative potential for precision-guided craniofacial therapy and regenerative dentistry.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1112-1125"},"PeriodicalIF":5.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13403293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201855","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":"Corrigendum to Redistribution Effect of Demineralized Dentin on Hydrophobic Monomers.","authors":"","doi":"10.1177/00220345261460818","DOIUrl":"10.1177/00220345261460818","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1235"},"PeriodicalIF":5.9,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229865","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}