{"title":"Corrigendum to Molecular Profiling of Odontoclasts during Physiological Tooth Replacement","authors":"","doi":"10.1177/00220345251384972","DOIUrl":"https://doi.org/10.1177/00220345251384972","url":null,"abstract":"","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"1 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209960","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}
L Huang,X Yang,Z Bai,Y Lu,J Bian,H Xie,C Chen,K Chen
{"title":"The Remineralization Potential of Resveratrol and Cucurbit[n]uril.","authors":"L Huang,X Yang,Z Bai,Y Lu,J Bian,H Xie,C Chen,K Chen","doi":"10.1177/00220345251350135","DOIUrl":"https://doi.org/10.1177/00220345251350135","url":null,"abstract":"The degradation of exposed collagen fibers in the deep layers of dentin during bonding procedures hampers its durability. Inducing the remineralization of demineralized dentin areas and inhibiting collagen degradation can improve bonding durability. Resveratrol, a natural polyphenol, has garnered attention for its positive effects on bonding durability. The positive effects on dentin remineralization and matrix metalloproteinase (MMP) inhibition are concentration dependent; high concentrations increase cytotoxicity. This study investigated the use of complexes of resveratrol and cucurbit[n]uril (Q[6] and Q[7]) to maintain adequate concentrations and achieve a stable rate of release in the deep dentin layers without causing cytotoxicity. Resveratrol and Q[n] complexes (Res@Q[n]) were prepared and their structures and the extent of resveratrol release were examined using analytical chemistry methods and quantum chemical analysis. In addition, the effects of resveratrol and the complexes of Res@Q[n] on cell cytotoxicity, recombinant type I collagen and dentin mineralization, microtensile bond strength (µTBS), nanoleakage, rhMMP-9 colorimetric assays, and in situ zymography were compared. Resveratrol was stably released from the Res@Q[n] complexes for nearly a month, reducing the cell cytotoxicity of high concentrations of the polyphenol, exhibiting stronger inhibition of MMPs, and facilitating more pronounced remineralization of recombinant type I collagen and dentin. Pretreating the dentin surface with complexes significantly increased the µTBS values and reduced nanoleakage and MMP activity before and after aging compared with single resveratrol. In conclusion, Res@Q[n] complexes can promote the continuous stability of the hybrid layer and improve the durability of dentin bonding compared with resveratrol alone without inducing cytotoxicity.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"1 1","pages":"220345251350135"},"PeriodicalIF":7.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209152","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}
X Li,Z Cao,X Chen,Y Xu,H Liu,X Wang,J Wang,L Hu,S Wang
{"title":"Salivary Nitrate Maintains Mucosal Homeostasis via the Sialin-Neuropeptide Axis.","authors":"X Li,Z Cao,X Chen,Y Xu,H Liu,X Wang,J Wang,L Hu,S Wang","doi":"10.1177/00220345251362203","DOIUrl":"https://doi.org/10.1177/00220345251362203","url":null,"abstract":"While saliva critically maintains oral homeostasis and accelerates mucosal repair, the molecular mediators driving this regenerative capacity remain unclear. Here, we identify salivary nitrate as a neuromodulatory signal coordinating oral mucosal regeneration through sensory neuron activation. In a palatal wound model, salivary nitrate depletion (via bilateral submandibular duct ligation or dietary restriction) impaired wound healing, characterized by reduced epithelial proliferation, aberrant collagen organization, and suppressed vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) expression-phenotypes rescued by nitrate supplementation. Transcriptomic profiling revealed that both nitrate-dependent upregulation of Rnf112 and the enhancement of the mucin type O-glycan biosynthesis pathway were mechanistically linked to myelinated sensory nerve modulation. Crucially, salivary nitrate promoted the reinnervation of myelinated sensory nerve fibers, upregulated the nitrate transporter sialin (Slc17a5), and stimulated the secretion of regenerative neuropeptides including calcitonin gene-related peptide, vasoactive intestinal peptide, and neuropeptide Y. In vitro, sialin knockdown abolished nitrate-induced cell proliferation and neuropeptide release in H4 cells while disrupting O-glycosylation, a key posttranslational modification for mucosal barrier function. Sensory neuron-specific sialin knockout mice (Slc17a5∆Trpv1, cKO) exhibited impaired neuropeptide release and failed to respond therapeutically to nitrate, confirming the indispensable role of sialin. These findings establish a sialin-dependent sensory neuropeptide axis wherein nitrate activates sensory neurons to drive mucosal regeneration, providing both mechanistic understanding of neuroepithelial crosstalk and a druggable target for tissue repair strategies.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"50 1","pages":"220345251362203"},"PeriodicalIF":7.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103452","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}
{"title":"GCN2-Mediated Integrated Stress Response Attenuates Periodontitis.","authors":"D Huang,Q Li,S Peng,Y Li,Q Yin,X Yang,X Gan,Y Wang,X Li,Y Zhao,Y Guo,W Lin,Y Li,N Feng,Q Yuan","doi":"10.1177/00220345251363525","DOIUrl":"https://doi.org/10.1177/00220345251363525","url":null,"abstract":"The integrated stress response (ISR), regulated by general control nonderepressible 2 (GCN2), is essential for maintaining tissue homeostasis, yet its role in periodontitis remains poorly understood. Here, through transcriptomic analysis and immunohistochemistry of gingival biopsies from patients and a ligature-induced mouse periodontitis model, we demonstrate that GCN2-mediated ISR is activated in both human and mouse periodontitis and mainly functioned in macrophages. Using Gcn2-/- mice, we show that Gcn2 deletion exacerbates gingival inflammation and bone loss in experimental periodontitis. Mechanistically, bulk RNA-seq and in vitro assays revealed that the loss of GCN2 impairs autophagy and leads to overactivation of the NLRP3/CASPASE1 inflammasome pathway. Notably, local administration of halofuginone, a GCN2 activator, mitigates oral inflammation and tissue destruction in a GCN2-dependent manner. In summary, our work highlights the protective role of the GCN2-mediated ISR in oral mucosa and indicates GCN2 as a promising therapeutic target for periodontitis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"1 1","pages":"220345251363525"},"PeriodicalIF":7.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103451","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}
K Martin,R Dabaja,M J Mianecki,A Sheikh,V Maglaras,M H A Saleh,J T Decker,A M Decker
{"title":"Periodontitis Leads to Systemic Bone Loss through Neutrophil Reprogramming.","authors":"K Martin,R Dabaja,M J Mianecki,A Sheikh,V Maglaras,M H A Saleh,J T Decker,A M Decker","doi":"10.1177/00220345251360752","DOIUrl":"https://doi.org/10.1177/00220345251360752","url":null,"abstract":"Periodontitis is a chronic oral inflammatory disease characterized by alveolar bone loss. Other diseases, such as osteoporosis, cardiovascular disease, and diabetes, can exacerbate its progression. These chronic diseases also have systemic effects that vary in frequency in men and women. Thus, this study sought to determine if periodontitis induced sex-specific changes in long bones. Periodontitis was induced by tying a 5-0 silk suture around the second maxillary molar of 6- to 8-wk-old male and female C57BL/6J mice. Ligatures were left in place for 7 d or 21 d, and the tibia was subsequently collected for characterization using micro-computed tomography, flow cytometry, and proteomics analysis. Female mice exhibited sustained trabecular and cortical bone loss through day 21, whereas males recovered from any bone loss observed at day 7. Flow cytometry and proteomics analysis indicated that an increased neutrophil response contributes to this bone loss by upregulating pathways associated with neutrophil extracellular trap (NET) formation and reactive oxygen species production. Eliminating NET generation using a Padi4-deficient mouse eliminated the bone loss phenotype during periodontitis. This study suggests that the neutrophil-driven pattern of bone loss observed in female mice, as well as the higher prevalence of osteoporosis in women, may highlight a potential mechanism by which periodontitis exacerbates systemic bone loss.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"128 1","pages":"220345251360752"},"PeriodicalIF":7.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089870","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}
J R H Tay,U Cooray,A Chan,M S Tonetti,G G Nascimento,M A Peres
{"title":"Perceived Masticatory Function and Mortality: A Causal Study.","authors":"J R H Tay,U Cooray,A Chan,M S Tonetti,G G Nascimento,M A Peres","doi":"10.1177/00220345251363851","DOIUrl":"https://doi.org/10.1177/00220345251363851","url":null,"abstract":"Masticatory function has been implicated in overall health decline, making it a potential target for public health interventions. We aimed 1) to assess whether perceived masticatory function is associated with all-cause mortality and 2) to quantify the impact of perceived masticatory function on all-cause mortality with a doubly robust causal inference approach. Data from a nationally representative longitudinal study of older people in Singapore were utilized. Perceived masticatory function was treated as a time-varying exposure (measured at the first 2 time points). It was categorized into 6 groups, ranging from group 1 (able to chew the toughest foods) to group 6 (unable to chew even the softest foods), reflecting increasing levels of chewing difficulty. All-cause mortality information until December 31, 2015, was assessed. Multivariable Cox regression models assessed the association between perceived masticatory function and all-cause mortality. Then, the longitudinal modified treatment policies approach was applied to estimate the effect of hypothetical preventive scenarios to preserve perceived masticatory function on mortality over 6 y. A total of 4,990 individuals were included in the analysis. The mean age at baseline was 72.8 y (SD, 8.1). For each level decrease in perceived masticatory function, the hazard ratio was 1.09 (95% CI, 1.05 to 1.14; P < 0.05). When perceived masticatory function was dichotomized into a binary variable with group 1 (no chewing difficulty) vs groups 2 to 6 (any level of difficulty), the hazard ratio was 1.25 (95% CI, 1.10 to 1.43; P < 0.05). The best hypothetical preventive scenario where all participants preserved maximum perceived masticatory function throughout the follow-up increased survival probability by 3% (relative risk, 1.03; 95% CI, 1.01 to 1.05; P < 0.05). Increased perceived masticatory function is associated and causally linked with reduced all-cause mortality among older adults in an Asian population. Policies aimed at preserving perceived masticatory function may be beneficial for older people's longer life spans and healthy life expectancy.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"75 1","pages":"220345251363851"},"PeriodicalIF":7.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059086","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}
A Lövgren,P Liv,J Durham,D A G Goncalves,F P Kapos,S F Kothari,M Drangsholt,C C Peck,C M Visscher,L Ong,P Svensson
{"title":"Disability Weights for Global Burden Estimation of Orofacial Pain.","authors":"A Lövgren,P Liv,J Durham,D A G Goncalves,F P Kapos,S F Kothari,M Drangsholt,C C Peck,C M Visscher,L Ong,P Svensson","doi":"10.1177/00220345251363852","DOIUrl":"https://doi.org/10.1177/00220345251363852","url":null,"abstract":"The global burden of orofacial pain (OFP), including temporomandibular disorders (TMDs), has never been estimated due to lacking disability weights (DWs). This is a significant limitation in the World Health Organization's goals for oral health. The present study presents DWs with directions for the development of corresponding health state descriptions. We used general population data on OFP and TMD (n > 180,000) with linked data on health-related quality of life from the Short Form Health Survey (SF-36; n > 110,000). From the SF-36 sum scores, a cumulative DW was mapped, and condition-specific DWs adjusted for common risk factors were calculated. Pain disability and related self-reported clinical characteristics were presented descriptively in a subsample of 300 individuals. In the study sample (n = 26,253, 49.9% women), participants with OFP reported significantly lower scores on the mental and physical components of the SF-36 when compared with pain-free individuals (P < 0.001), as did individuals with TMD as compared with those without TMD (P < 0.001). After adjusting for the presence of common health states, the mean DW was 0.024 (95% CI, 0.011 to 0.038) for OFP and 0.026 (95% CI, 0.016 to 0.038) for TMD. Individuals with higher pain disability reported higher pain intensity as well as increased pain catastrophizing and functional jaw limitations. Our findings demonstrate a feasible solution for estimating DW for OFP and TMD as an important step toward incorporation of these conditions into the Global Burden of Disease study and suggest a greater impact of pain than other common oral diseases. Further efforts are needed to develop lay descriptions and validate DW findings in other populations.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"313 1","pages":"220345251363852"},"PeriodicalIF":7.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059218","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}
A A Akinkugbe,C-Y S Hsu,C Lesseur,V Midya,K H Tan,K Y Jerry Chan,J G Eriksson,S-Y Chan,Y S Chong,Y S Lee,D Wang,J Huang,R O Wright,N Karnani,K M Godfrey,A L Teh,R J Wright
{"title":"Smoking-Associated DNA Methylation and Offspring Caries Experience: Findings from the GUSTO Study.","authors":"A A Akinkugbe,C-Y S Hsu,C Lesseur,V Midya,K H Tan,K Y Jerry Chan,J G Eriksson,S-Y Chan,Y S Chong,Y S Lee,D Wang,J Huang,R O Wright,N Karnani,K M Godfrey,A L Teh,R J Wright","doi":"10.1177/00220345251362803","DOIUrl":"https://doi.org/10.1177/00220345251362803","url":null,"abstract":"Self-reported smoking during pregnancy is subject to measurement error, bringing into question previously reported associations with offspring caries experience. We evaluated whether a previously identified prenatal smoking-associated DNA methylation (DNAm) signature, and separately gestational smoking indexed through self-report and plasma cotinine, was associated with offspring caries. The Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort (n = 577 mother-child dyads, recruited from June 2009-September 2010) ascertained gestational smoking exposure (by questionnaires and plasma cotinine), DNAm (using umbilical cord tissue), and child dental caries (by clinical examinations at age 3 y). We used zero-inflated Poisson regression to evaluate whether a weighted smoking-associated DNAm risk score (wMRSDNAm) was associated with the count of tooth surface caries, adjusted for maternal age, education, ethnicity, breastfeeding, preterm status, child sex, and toothbrushing frequency. Of the women, 53% were never smokers and 3% were heavy smokers; children had a mean (standard deviation) of 2.47 (5.20) decayed, missing, and filled surfaces. The mean wMRSDNAm for the 16 CpGs included was -0.21 (0.02), with an interquartile range of 0.02. Each additional IQR of wMRSDNAm was associated with a 20% higher adjusted caries experience risk, relative risk (RR) (95% confidence interval [CI]) = 1.20 (1.10, 1.31), and a lower adjusted odds of excess zeros, odds ratio (95% CI) = 0.91 (0.70, 1.17). Children of mothers who smoked during gestation (based on self-report/cotinine) also had higher adjusted caries experience risk: relative risk (RR) (95% CI) = 1.31 (1.11, 1.55) and RR (95% CI) = 1.12 (0.81, 1.54) for light and heavy smoking, respectively. These findings corroborate a link between prenatal smoking and offspring caries and provide novel information of a positive association between maternal smoking-associated DNAm risk scores and greater offspring caries experience. While replication in independent studies is warranted as these results are based on CpGs derived from umbilical cord DNA, these findings point to a need for greater smoking cessation support.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"20 1","pages":"220345251362803"},"PeriodicalIF":7.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059085","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}
{"title":"Acid α-Glucosidase Impairs Diabetic Bone Regeneration via Altering Macrophage Polarization.","authors":"S C Yu,J F Liang,Y Li,S Y Ma,J Sun,A Li,D D Pei","doi":"10.1177/00220345251350658","DOIUrl":"https://doi.org/10.1177/00220345251350658","url":null,"abstract":"The diabetic microenvironment intensifies M1-type macrophage-mediated inflammation and impairs bone regeneration. Glycophagy-a process of glycogen-selective autophagy that degrades intracellular glycogen into glucose-is essential for maintaining glucose homeostasis under metabolic stress. The role of glycophagy in regulating M1-type polarization remains unclear. In this study, we found that M1-type polarization correlated with increased glycophagy in a diabetic mandibular bone defect model. Proteomic analysis revealed the involvement of the glycophagy mediator acid α-glucosidase (GAA) in M1-type polarization in diabetic bone callus. Mechanistically, the upregulation of GAA drove M1-type polarization to inhibit osteogenesis under high-glucose conditions by activating the mTORC1 signaling pathway. Transplant of GAA-silenced macrophages restored the osteogenic capability in mandibular injury in diabetic rats. In conclusion, our study unravels the regulation of a fundamental mechanism of M1-type polarization by the glycophagy mediator GAA, providing insights relevant for promoting bone generation in diabetic individuals.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"35 1","pages":"220345251350658"},"PeriodicalIF":7.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025372","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}
L S Ma,Z S Shen,S Y Huang,M Y Li,D Tian,D Zhang,S L Wang
{"title":"Therapeutic Potential of TCRαβ+CD4-CD8- T Cells in Periodontitis.","authors":"L S Ma,Z S Shen,S Y Huang,M Y Li,D Tian,D Zhang,S L Wang","doi":"10.1177/00220345251362744","DOIUrl":"https://doi.org/10.1177/00220345251362744","url":null,"abstract":"Periodontitis, a pervasive chronic inflammatory disorder, is distinguished by the progressive degradation of periodontal tissues and alveolar bone. Despite remarkable progress in understanding the pathogenesis of periodontitis, the involvement of TCRαβ+CD4-CD8- T cells, also known as double-negative T (DNT) cells, in the pathophysiology of this disease has not been thoroughly investigated. In this study, we observed a significant reduction in the frequency of TCRαβ+ DNT cells within the gingival tissues of patients afflicted with periodontitis when compared with healthy individuals. Employing a murine model, we demonstrated that the therapeutic administration of TCRαβ+ DNT cells resulted in a reduction of alveolar bone resorption and a decrease in inflammatory biomarkers, with the most significant effects observed at lower cell doses. Histological examination and gene expression analysis revealed a notable attenuation in the expression levels of proinflammatory cytokines. Furthermore, transcriptomic profiling elucidated the downregulation of pathways associated with neutrophil activation and interleukin-17 signaling, which are critical in the inflammatory cascade of periodontitis. Both in vitro and in vivo experiments underscored the pivotal role of perforin in TCRαβ+ DNT cells, which is essential for modulating periodontal inflammation and preventing alveolar bone loss. Collectively, our findings suggest that TCRαβ+ DNT cell therapy may represent a promising novel therapeutic strategy for periodontitis, providing valuable insights into the development of innovative treatment modalities for this prevalent oral health condition.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"44 1","pages":"220345251362744"},"PeriodicalIF":7.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025374","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}