R V Harris, V Lowers, J Green, R Kirby, J Hennessy, J E Clarkson, G Burnside
{"title":"RETURN Randomized Controlled Trial to Increase Adult Routine Dental Visits.","authors":"R V Harris, V Lowers, J Green, R Kirby, J Hennessy, J E Clarkson, G Burnside","doi":"10.1177/00220345261425929","DOIUrl":"https://doi.org/10.1177/00220345261425929","url":null,"abstract":"<p><p>Groups with low socioeconomic status are less likely to make planned dental visits even though routine attenders have fewer caries and less tooth loss. Because behavioral interventions positioned in urgent dental care may improve health and inequalities, RETURN, which involved a nurse conversation supported by videos, booklets, and goal/action-plan setting, was developed. The objective of this study was to investigate the effectiveness of the RETURN intervention at increasing planned dental visits and lessening the oral health impact. Adults attending 14 National Health Service urgent dental services were recruited to a randomized controlled trial and followed up after 6, 12, and 18 mo. Co-primary outcomes were (1) planned visits at 12 mo as measured by Business Services Authority (BSA) data and (2) Oral Health Impact Profile (OHIP) summary score at 12 mo adjusted for baseline. Of the 1,176 consenting adults who were randomized, 591 were allocated to the RETURN group. More than half (55.2%, 315 intervention; 54.7%, 310 control) lived in the lowest Index Multiple Deprivation decile. RETURN participants had a 20% greater odds of planned care as recorded by the BSA at 12 mo (odds ratio [OR] = 1.21; 97.5% confidence interval [CI] = 0.86, 1.70; <i>P</i> = 0.217). There was a reduction (improvement) in OHIP scores at 12 mo in both groups (RETURN group, mean = -7.4, standard deviation [SD] = 12.9; control group, mean = -6.2, SD = 12.9). The least squares mean of the RETURN Modified Dental Anxiety Score decreased with time (anxiety improved) whereas it increased (worsened) in the control group (Modified Dental Anxiety Scale time and treatment group interaction = -0.01; CI = -0.03, 0.00; <i>P</i> = 0.027). RETURN participants had a more than 3 times greater odds of attempting to make an appointment, with the treatment effect increasing with time (at 18 mo: OR = 3.39; 95% CI = 1.83, 6.27; <i>P</i> = 0.0001). We are moderately certain RETURN produced small, consistently favorable effects on routine visits, oral health impact, and dental anxiety despite limited-service availability. RETURN also significantly increased attempts to make routine appointments even in a disadvantaged cohort. This supports integrating behavioral support alongside service reforms to support the transition into continuing care and the optimum use of resources.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261425929"},"PeriodicalIF":5.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848022","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":"Oral Health-Related Quality of Life and Social Engagement: Gender Differences.","authors":"P Sung, Y Zhang, M Kang, S H Kang","doi":"10.1177/00220345261438375","DOIUrl":"https://doi.org/10.1177/00220345261438375","url":null,"abstract":"<p><p>Growing evidence supports the interdependence between oral health-related quality of life (OHRQoL) and formal social engagement (FSE) in later life. However, the causal direction of this relationship and potential gender differences therein remain underexplored. This study, informed by social causation and health selection perspectives within a social determinants of health framework, examines gender-specific patterns in the reciprocal relationship between OHRQoL and FSE among older adults in South Korea. A random-intercept cross-lagged panel model was applied to 3-wave panel data (2018, 2020, 2022) from 6,106 Korean adults aged ≥55 y. OHRQoL was assessed by the Geriatric Oral Health Assessment Index, validated for the Korean population. FSE was measured by the frequency of participation in structured organizational activities. The analysis identified significant bidirectional associations between OHRQoL and FSE at the within-person level, with distinct gender-specific patterns. Among men, better-than-usual OHRQoL predicted subsequent FSE, but the reverse path was not significant (health selection only). Among women, significant bidirectional associations were observed (social causation and health selection). These findings suggest gender-tailored interventions: alleviating oral health barriers to facilitate social reengagement for both genders, while leveraging social engagement to enhance OHRQoL specifically for women.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261438375"},"PeriodicalIF":5.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848005","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":"New Speed-Sintered CaO-Zirconia for Strong, Tough, Translucent Restorations.","authors":"A Vettorel, B V Meerbeek, J Vleugels, F Zhang","doi":"10.1177/00220345261435597","DOIUrl":"https://doi.org/10.1177/00220345261435597","url":null,"abstract":"<p><p>The demand for rapid, reliable, and esthetic ceramic restorations continues to drive innovation in dental materials and chairside manufacturing technology. However, conventional yttria-stabilized zirconia presents an inherent trade-off between mechanical and optical properties, with moderate fracture toughness ≤5 MPa·m<sup>1/2</sup>. This study investigates the feasibility of chairside speed-sintering of a 4.5 mol% CaO-stabilized tetragonal zirconia polycrystal (4.5Ca-TZP), focusing on its microstructure, mechanical reliability, translucency, and aging resistance. Nano-sized 4.5Ca-TZP powders were compacted and speed-sintered within 60 min at 1,250 °C to 1,350 °C. Four sintering groups were evaluated (<i>n</i> = 20/group for density; <i>n</i> = 1 for grain size; <i>n</i> = 10 for hardness; <i>n</i> = 3 for Rietveld refinement; <i>n</i> = 5 for fracture toughness, translucency, and aging; <i>n</i> = 30 for biaxial strength and Weibull analysis) with statistical differences set at α = 0.05. Speed-sintering gave rise to fully dense ceramics (≥99% relative density) with a homogeneous, fine microstructure (<200 nm) and negligible monoclinic content (≤2 vol%). The ceramics demonstrated excellent mechanical reliability, exhibiting a characteristic strength of ≥1.1 GPa and a Weibull modulus ≥11. Hardness slightly decreased with increasing temperature, whereas translucency reached its maximum (≈22) at 1,250 °C. Indentation testing revealed the absence of radial cracks in specimens sintered above 1,300 °C. No tetragonal-to-monoclinic transformation occurred after 20 h of hydrothermal aging at 134 °C, demonstrating aging resistance. Compared with conventionally sintered 4.5Ca-TZP, speed-sintered ceramics showed comparable translucency and strength with enhanced mechanical reliability but significantly lower fracture toughness of >5 MPa·m<sup>1/2</sup>. Overall, this work demonstrates that 4.5Ca-TZP can be speed-sintered to achieve fully dense zirconia with performance exceeding that of conventional 3Y-TZP, providing a tougher alternative zirconia restoration. A computer-aided design/computer-aided manufacturing-milled crown fabricated as a proof of concept showed isotropic shrinkage, supporting its potential for chairside application, while further investigation of long-term resistance, large-scale manufacturing, and dimension limitations is required to confirm clinical applicability.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261435597"},"PeriodicalIF":5.9,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825053","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":"Dental Service Use during the 30 Years before Type 2 Diabetes Onset.","authors":"E Raittio, F V Bitencourt, V Baelum, R Lopez","doi":"10.1177/00220345261432661","DOIUrl":"https://doi.org/10.1177/00220345261432661","url":null,"abstract":"<p><p>Although the association between type 2 diabetes mellitus (T2DM) and oral disease has been widely investigated, little is known about long-term dental care patterns before T2DM diagnosis. This study therefore described dental service utilization up to 30 y prior to the incidence of a T2DM, compared with age- and sex-matched controls. This matched cohort study used nationwide Danish registry data on individuals born between 1950 and 1970 who maintained permanent residency from 1990 to 2021. For each person with incident T2DM in 2021, 4 age- and sex-matched controls were selected. Incident T2DM was identified based on the purchases of glucose-lowering medication or a hospital diagnosis. Dental service utilization included receipt of any dental care, periodontal, endodontic, restorative, and extraction treatments. Time trends were analyzed using logistic and Poisson regression models. Among 1,231,846 eligible individuals, 10,205 had incident T2DM in 2021 and were matched to 40,820 controls. The incident T2DM population was less likely to receive dental care in a calendar year than the controls and had 2.4 (95% confidence interval [CI]: 2.2 to 2.6) fewer years with a dental visit in the years preceding the diagnosis. The individuals with incident T2DM were more likely to have received periodontal (risk ratio: 1.08, 95% CI 1.05 to 1.12) and endodontic treatments (risk ratio: 1.14, 95% CI: 1.11 to 1.17), and they had received more extractions (rate ratio: 1.32, 95% CI: 1.29 to 1.36) and slightly more restorative treatments (rate ratio: 1.02, 95% CI: 1.00 to 1.04) during a calendar year over the period preceding the T2DM diagnosis than did the controls. More than 30 y prior to diagnosis, individuals who developed T2DM were less likely to attend dental care, but when they did attend, they underwent more complex and invasive procedures. These findings support a common risk factor approach to prevent T2DM and oral diseases at the clinical, health system, and policy levels.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261432661"},"PeriodicalIF":5.9,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825102","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":"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":"10.1177/00220345261424748","DOIUrl":"https://doi.org/10.1177/00220345261424748","url":null,"abstract":"<p><p>The purpose of this study was to determine the average treatment effect (ATE) of tooth extraction before radiotherapy on the risk of osteoradionecrosis (ORN) in patients with head and neck cancer (HNC) and to estimate the conditional average treatment effect (CATE) to characterize heterogeneous treatment effects (HTE). In this retrospective cohort study of adults with HNC treated with curative radiotherapy from 2011 to 2018 with ongoing follow-up, the intervention was the extraction of at least 1 tooth before radiotherapy, and the outcome was ORN (ClinRad grade ≥1). Twenty sociodemographic and clinical covariates were recorded. A causal survival forest targeting restricted mean survival time (RMST) was trained with 100 repetitions of 5-fold cross-validation. Calibration used out-of-fold augmented inverse probability weighting (AIPW) scores as pseudo-outcomes, and treatment prioritization was assessed using the rank-weighted average treatment effect (RATE). A best linear projection regression identified covariates with direct associations to the predicted benefit. Among 2,466 patients, 810 underwent preradiotherapy extraction, and 183 developed ORN during the follow-up. The ATE was not significant at -0.26 mo (95% confidence interval [CI]: -0.68 to 0.17). However, the CATE distributions revealed substantial HTE, with patients in the lowest quartile (Q1) experiencing harm and those in the highest quartile (Q4) deriving benefit. Calibration against AIPW scores confirmed median RMST differences of -1.47 mo in Q1 and +0.94 mo in Q4. The RATE was positive at 1.10 (95% CI: 0.04 to 2.15). Best linear projection identified Eastern Cooperative Oncology Group performance status 1 to 4 versus 0 (β = 2.68; 95% CI: 0.19 to 5.17) and periodontal grade III-IV versus 0 (β = 4.33; 95% CI: 1.05 to 7.60) as independent modifiers of benefit. Radiation dose had a nonlinear association with treatment effect. If preradiotherapy tooth extraction was applied across all eligible patients, it would not alter the overall risk of ORN. However, individualized treatment effects varied, with some patients benefiting and others harmed, underscoring the importance of targeted interventions.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"220345261424748"},"PeriodicalIF":5.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147438590","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}
L G Do, A Sawyer, A J Spencer, S Leary, J K Kuring, A Jones, T Le, C E Reece, D H Ha
{"title":"Response to Letter to the Editor: \"Early Childhood Exposures to Fluorides and Cognitive Neurodevelopment: A Population-Based Longitudinal Study\".","authors":"L G Do, A Sawyer, A J Spencer, S Leary, J K Kuring, A Jones, T Le, C E Reece, D H Ha","doi":"10.1177/00220345251390898","DOIUrl":"10.1177/00220345251390898","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"278"},"PeriodicalIF":5.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794925","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}
N Alkhars, S Manning, N Al Jallad, Y Zeng, T T Wu, C Fogarty, M Mendoza, E van Wijngaarden, D T Kopycka-Kedzierawski, R Billings, K Fiscella, H Koo, J Xiao
{"title":"Birth Cohort Study Identifies <i>Candida albicans</i> as a Risk Factor for Dental Caries.","authors":"N Alkhars, S Manning, N Al Jallad, Y Zeng, T T Wu, C Fogarty, M Mendoza, E van Wijngaarden, D T Kopycka-Kedzierawski, R Billings, K Fiscella, H Koo, J Xiao","doi":"10.1177/00220345251340040","DOIUrl":"10.1177/00220345251340040","url":null,"abstract":"<p><p><i>Candida albicans</i> has been implicated as a potential cariogenic microorganism, yet no prospective longitudinal studies have examined its role in severe early childhood caries (S-ECC). This study aimed to evaluate the association between oral <i>C. albicans</i> and the onset of S-ECC in a longitudinal setting. This prospective birth cohort study (2018 to 2023) enrolled 186 low-income pregnant women in their third trimester in Western New York, United States. Overall, 160 eligible infants born to these women were followed from birth to 2 y at 7 time points. Oral samples were collected to assess <i>Candida</i> species (<i>C. albicans</i>, <i>Candida krusei</i>, and <i>Candida glabrata</i>) and <i>Streptococcus mutans</i>. The primary outcome was the onset of S-ECC. Two-step LASSO (least absolute shrinkage and selection operator)-penalized logistic regression models were developed to identify predictive factors for S-ECC from 234 covariates grouped by their proximal association with S-ECC: infant oral microorganisms, biological-environmental factors, and maternal characteristics. Logistic regression was used to validate the association between <i>C. albicans</i> and S-ECC. Among the 118 children who completed the study, 28% developed S-ECC. The racial background of the cohort was 57% Black, 21% White, and 22% other. Oral <i>C. albicans</i> colonized in 12% of infants at 1 wk, peaking at 57% by 18 mo. Salivary <i>C. albicans</i> was associated with a 4.47-fold increased risk for S-ECC (odds ratio [OR]; 95% CI, 1.28 to 15.58; <i>P</i> = 0.02), in addition to other risk factors, including plaque score (OR, 5.19; 95% CI, 2.10 to 12.83) and salivary <i>S. mutans</i> (OR, 9.74; 95% CI, 2.27 to 41.79). <i>C. albicans</i> demonstrated strong time sensitivity in predicting S-ECC as early as 1 mo, contrasting with <i>S. mutans</i>, which exhibited predictive ability after 1 y. Oral <i>C. albicans</i> could serve as a novel biological marker for predicting ECC risk in infancy, shining a light on opportunities to develop innovative caries-predictive and preventive strategies targeting fungal contributions in pediatric care settings.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1470-1478"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12757439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510066","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}
C Feng, X Dou, S-R Li, X Xu, Z Dang, Z Jiang, E Jiang, Z Shang
{"title":"Single-Cell Insights into Unicystic and Solid Ameloblastoma Heterogeneity.","authors":"C Feng, X Dou, S-R Li, X Xu, Z Dang, Z Jiang, E Jiang, Z Shang","doi":"10.1177/00220345251340892","DOIUrl":"10.1177/00220345251340892","url":null,"abstract":"<p><p>The clinical classification of ameloblastoma (AM) plays a decisive role in the selection of treatment options, but the difference of single-cell landscape among clinical classifications is still unclear. At the same time, there is an urgent need to understand the key cell subtypes that determine the clinical subtypes. We characterized the single-cell transcriptional profiles of clinical subtypes of AM. We also characterized a pseudotime transition trajectory from immunoactive epithelial cells to vascular-associated fibroblasts, identifying key transcription factors involved in this process. Notably, we observed significant heterogeneity between M1 and M2 macrophages among the clinical subtypes of AM. Furthermore, our analysis revealed that metabolic disorder in AM was primarily driven by the metabolic disturbances in M1 and M2 macrophages. At the cellular communication level, we highlighted the role of M2 macrophages in mediating cell interactions, focusing on the RANKL/RANK pathway associated with osteoclast activity. Finally, we attempted to establish a unicystic AM-derived epithelial cell line and utilized it to construct an AM-like organoid model; we found that M2 macrophages competed with AM for L-cysteine to achieve cystic changes in the solid lesion. Our exploration of pathogenesis underlying various clinical types of AM advances our knowledge of AM heterogeneity, offering promising targets for novel therapeutic strategies.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1506-1516"},"PeriodicalIF":5.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144510067","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 Zhang, M Yuan, K Asam, Z Gong, T Xie, F Gleber-Netto, M D Santi, Y Kobayashi, E Shimizu, B Aouizerat, M Amit, M D Boada, Y Ye
{"title":"Perineural Invasion Exhibits Traits of Neurodegeneration.","authors":"M Zhang, M Yuan, K Asam, Z Gong, T Xie, F Gleber-Netto, M D Santi, Y Kobayashi, E Shimizu, B Aouizerat, M Amit, M D Boada, Y Ye","doi":"10.1177/00220345251334379","DOIUrl":"10.1177/00220345251334379","url":null,"abstract":"<p><p>Perineural invasion (PNI) frequently occurs in head and neck squamous cell carcinoma (HNSCC), which correlates with poor survival and induces intractable pain and numbness. There is no effective treatment for PNI or associated pain. To gain a better understanding of PNI at the molecular and cellular level, we produced an orthotopic, syngeneic mouse model of PNI by inoculating mouse oral cancer cells into the infraorbital nerve (ION), a nerve that is susceptible to cancer invasion in patients with HNSCC. Mice with PNI in the ION exhibited both evoked and spontaneous nociception and impaired oral function, mimicking human conditions. PNI resulted in a drastic reduction in the proportion and altered mechanical thresholds in mechanically sensitive trigeminal neurons; axon and myelin abnormalities, as well as phagocytic cells, were observed. The tumor bed is marked by CD4<sup>+</sup> and CD8<sup>+</sup> T cells, CD68<sup>+</sup> cells, and F4/80<sup>+</sup> macrophages, while CD4<sup>+</sup>, CD8<sup>+</sup>, and CD68<sup>+</sup> immune cells can be found surrounding the nerve. The intraneural niche is predominantly marked by CD68 that does not overlap with F4/80 but instead overlaps with NF200 and MPZ and occasionally with DAPI, suggesting these are likely phagocytic macrophages or Schwann cells. Finally, our RNA sequencing pathway analysis in mouse and human HNSCC found perturbed pathways in neuroinflammation, mitochondrial dysfunction, and cellular metabolism. Additionally, ION-PNI exhibits nerve degenerative features with perturbed pathways that are observed in Alzheimer, Parkinson, and prion diseases. In conclusion, we report a novel, anatomically relevant in vivo model that could be used to study the cellular and molecular mechanisms of PNI-induced neuropathies. Importantly, we found that PNI resembles neurodegenerative diseases with features of altered sensory transduction and conduction, neuroinflammation, and mitochondrial dysfunction, which may underlie peripheral neuropathies, such as pain.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1352-1360"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12678856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259698","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}
R Mahmoud, A Simon, J Luther, J Pothe, Y Du, C Nottmeier, E Okine, S Knauth, M G Lopez, E Bockamp, J Krivanek, A LeBlanc, J Helms, M Amling, M Kaucka, T Schinke, T Koehne, J Petersen
{"title":"Wnt1's Differential Effects on Craniofacial Bone and Tooth Development.","authors":"R Mahmoud, A Simon, J Luther, J Pothe, Y Du, C Nottmeier, E Okine, S Knauth, M G Lopez, E Bockamp, J Krivanek, A LeBlanc, J Helms, M Amling, M Kaucka, T Schinke, T Koehne, J Petersen","doi":"10.1177/00220345251336191","DOIUrl":"10.1177/00220345251336191","url":null,"abstract":"<p><p>The development of craniofacial bones and teeth relies heavily on the Wnt signaling pathway, yet the specific mechanisms and Wnt variants involved remain under continual investigation. Using publicly available single-cell sequencing data from the mouse incisor, we reveal <i>Wnt1</i> expression across dental structures and investigate its role using a <i>Col1a1</i>-dependent <i>Wnt1</i> transgenic mouse model. Inducing <i>Wnt1</i> early on affects craniofacial bone without disturbing tooth development, but prolonged embryonic induction leads to postnatal mortality with osteopetrosis-like bone overgrowth and malformed teeth. While tooth formation was initially unaffected by postnatal <i>Wnt1</i> induction, prolonged activation impaired tooth root formation and odontoblast differentiation, resulting in shortened roots and thinner dentin. Three-dimensional micro-computed tomography quantification reveal that both embryonic and postnatal activation of <i>Wnt1</i> significantly increase neural crest-derived craniofacial bone volume, whereas mesenchymal-derived craniofacial bones are unaffected. Importantly, osteoclastogenesis is suppressed by <i>Wnt1</i> in a dose-dependent manner, revealed through bulk RNA sequencing and in vitro experiments. These findings emphasize the differential effects of <i>Wnt1</i> on bone development based on origin and highlight its role in modulating osteoclast activity, indicating broader implications for craniofacial development and potential therapeutic avenues.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"1415-1424"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12508500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201249","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}