Pub Date : 2026-02-04DOI: 10.1177/00220345251396418
M. Charles-Ayinde, H. Benzian, J.E. Gallagher, S. Imazato, C.H. Fox
{"title":"The Bangkok Declaration: A Global Mandate for Oral Health Research and Universal Health Coverage","authors":"M. Charles-Ayinde, H. Benzian, J.E. Gallagher, S. Imazato, C.H. Fox","doi":"10.1177/00220345251396418","DOIUrl":"https://doi.org/10.1177/00220345251396418","url":null,"abstract":"","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"20 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115814","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}
Pub Date : 2026-01-30DOI: 10.1177/00220345251408838
J Xu,Y Lei,M Pan,Z Li,W Lao,Q Luo,X Li
Inadequate dentin bonding persists as a major cause of secondary caries and restoration failure, accounting for >60% of global dental restorative costs. Prevailing adhesion theory attributes this to challenges in displacing water from the demineralized dentin matrix (DDM) to infiltrate hydrophobic monomers. However, techniques such as ethanol-wet bonding, which eliminate water, yield only partial improvement, suggesting limitations in this water-centric view. Using chromatography equivalence modeling and Nile red molecular tracing, we identified a solvent-independent redistribution effect exerted by the DDM itself on BisGMA, which was selected as a representative hydrophobic multifunctional monomer. This effect causes BisGMA to concentrate preferentially in the adhesive layer rather than infiltrating the 3-dimensional DDM uniformly, resulting in a sharply attenuated penetration profile and a defective hybrid layer. We demonstrate that interface-confined water exacerbates this effect by swelling the DDM, amplifying its polarity, and increasing viscous resistance, whereas free water has minimal influence. Crucially, DDM reconstruction mitigates the effect and improves infiltration. Our findings establish that the DDM's inherent properties, not merely the water that it contains, fundamentally limit hydrophobic monomer infiltration, challenging the existing paradigm and advocating for a new interface-focused framework in dentin bonding.
{"title":"Redistribution Effect of Demineralized Dentin on Hydrophobic Monomers.","authors":"J Xu,Y Lei,M Pan,Z Li,W Lao,Q Luo,X Li","doi":"10.1177/00220345251408838","DOIUrl":"https://doi.org/10.1177/00220345251408838","url":null,"abstract":"Inadequate dentin bonding persists as a major cause of secondary caries and restoration failure, accounting for >60% of global dental restorative costs. Prevailing adhesion theory attributes this to challenges in displacing water from the demineralized dentin matrix (DDM) to infiltrate hydrophobic monomers. However, techniques such as ethanol-wet bonding, which eliminate water, yield only partial improvement, suggesting limitations in this water-centric view. Using chromatography equivalence modeling and Nile red molecular tracing, we identified a solvent-independent redistribution effect exerted by the DDM itself on BisGMA, which was selected as a representative hydrophobic multifunctional monomer. This effect causes BisGMA to concentrate preferentially in the adhesive layer rather than infiltrating the 3-dimensional DDM uniformly, resulting in a sharply attenuated penetration profile and a defective hybrid layer. We demonstrate that interface-confined water exacerbates this effect by swelling the DDM, amplifying its polarity, and increasing viscous resistance, whereas free water has minimal influence. Crucially, DDM reconstruction mitigates the effect and improves infiltration. Our findings establish that the DDM's inherent properties, not merely the water that it contains, fundamentally limit hydrophobic monomer infiltration, challenging the existing paradigm and advocating for a new interface-focused framework in dentin bonding.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"8 1","pages":"220345251408838"},"PeriodicalIF":7.6,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089134","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}
Pub Date : 2026-01-21DOI: 10.1177/00220345251406260
N S Jakubovics,F Schwendicke,V Muirhead,J Feine
{"title":"Nothing to Hide: The Merits of Open Data in Dental Research.","authors":"N S Jakubovics,F Schwendicke,V Muirhead,J Feine","doi":"10.1177/00220345251406260","DOIUrl":"https://doi.org/10.1177/00220345251406260","url":null,"abstract":"","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"65 1","pages":"220345251406260"},"PeriodicalIF":7.6,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005392","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}
Enamel mineralization critically depends on maturation-stage ameloblasts (M-ABs) regulating pH, protein secretion, and cell-matrix adhesion. However, the molecular mechanisms underlying these processes remain poorly understood. This study identifies the vacuolar-type H+-ATPase (V-ATPase) a3 subunit as a key regulator of enamel formation via its role in secretory lysosome trafficking. In a3 knockout (a3KO) mice and cultured ameloblasts, a3 is required for both lysosomal acidification and the directional transport of odontogenic ameloblast-associated protein (ODAM)-containing secretory lysosomes to the ruffled border membrane of M-ABs. At this site, ODAM is crucial for mediating ameloblast adhesion to the enamel matrix. Loss of a3 caused severe enamel hypomineralization, characterized by reduced matrix acidification, cystic enamel defects, abnormal ruffled border morphology, and ameloblast detachment from the mineralizing surface. In vitro, a3-deficient ameloblasts exhibited significantly impaired adhesion to hydroxyapatite, decreased ODAM expression, and suppressed lysosomal acidification, indicating a3 is functionally required for maintaining ameloblast function and polarity. Mechanistically, Rab27A served as an important adaptor linking a3-positive secretory lysosomes to the microtubule network, enabling their polarized movement toward the distal plasma membrane. Disruption of this a3-Rab27A axis in a3KO cells mislocalized secretory lysosomes and defective ODAM delivery into the enamel matrix, compromising enamel mineralization. These findings reveal a new mechanism by which a3 orchestrates lysosomal positioning and ODAM secretion in enamel-forming cells. By integrating proton transport with vesicular trafficking and adhesion protein delivery, a3 functions as a key regulator of enamel mineralization. This study provides new insights into the pathogenesis of enamel hypomineralization and identifies a3 and its associated pathways as potential therapeutic targets for treating developmental enamel defects.
{"title":"V-ATPase a3 Directs Secretory Lysosome Transport in Enamel Formation.","authors":"K Otsu,S Ikezaki,N Goto-Matsumoto,A Ikarashi,H Sano,H Ida-Yonemochi,H Ohshima,G-H Sun-Wada,Y Wada,M Nakanishi-Matsui,H Harada","doi":"10.1177/00220345251401512","DOIUrl":"https://doi.org/10.1177/00220345251401512","url":null,"abstract":"Enamel mineralization critically depends on maturation-stage ameloblasts (M-ABs) regulating pH, protein secretion, and cell-matrix adhesion. However, the molecular mechanisms underlying these processes remain poorly understood. This study identifies the vacuolar-type H+-ATPase (V-ATPase) a3 subunit as a key regulator of enamel formation via its role in secretory lysosome trafficking. In a3 knockout (a3KO) mice and cultured ameloblasts, a3 is required for both lysosomal acidification and the directional transport of odontogenic ameloblast-associated protein (ODAM)-containing secretory lysosomes to the ruffled border membrane of M-ABs. At this site, ODAM is crucial for mediating ameloblast adhesion to the enamel matrix. Loss of a3 caused severe enamel hypomineralization, characterized by reduced matrix acidification, cystic enamel defects, abnormal ruffled border morphology, and ameloblast detachment from the mineralizing surface. In vitro, a3-deficient ameloblasts exhibited significantly impaired adhesion to hydroxyapatite, decreased ODAM expression, and suppressed lysosomal acidification, indicating a3 is functionally required for maintaining ameloblast function and polarity. Mechanistically, Rab27A served as an important adaptor linking a3-positive secretory lysosomes to the microtubule network, enabling their polarized movement toward the distal plasma membrane. Disruption of this a3-Rab27A axis in a3KO cells mislocalized secretory lysosomes and defective ODAM delivery into the enamel matrix, compromising enamel mineralization. These findings reveal a new mechanism by which a3 orchestrates lysosomal positioning and ODAM secretion in enamel-forming cells. By integrating proton transport with vesicular trafficking and adhesion protein delivery, a3 functions as a key regulator of enamel mineralization. This study provides new insights into the pathogenesis of enamel hypomineralization and identifies a3 and its associated pathways as potential therapeutic targets for treating developmental enamel defects.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"87 1","pages":"220345251401512"},"PeriodicalIF":7.6,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005333","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}
Pub Date : 2026-01-21DOI: 10.1177/00220345251406559
A T M Dao,L G Do,N Stormon,H V Nguyen,D H Ha
The World Health Organization (WHO) recommends reducing free sugar intake (FSI) to below 10%, and ideally below 5%, of the estimated energy requirement (EER) to prevent noncommunicable diseases, including dental caries. Little progress has been made in lowering FSI to reduce early childhood caries (ECC) over the past few decades. Although sugar's impact on health is well established, no studies have quantified the extent to which reducing FSI to these thresholds would reduce decayed, missing, and filled surfaces (dmfs) scores. Data from 2,182 Australian children in the SMILE birth cohort were analyzed using G-computation analysis to estimate counterfactual dmfs if FSI at age 2 y had been reduced below 10% or 5% of the EER. A dose-response analysis using restricted cubic splines was also conducted to empirically assess thresholds by modeling dmfs at age 5 y as a function of continuous FSI. The G-computation results indicate that, in the general preschool population, reducing FSI to less than 10% or 5% of the EER would result in an absolute reduction (AR) in dmfs of 1.3 and 1.5, respectively, corresponding to attributable fractions among the exposed (AFE) of 84% and 97%. Among high-risk children, the estimation impact is even greater, with ARs in dmfs of 4.4 to 4.5 and AFEs ranging from 75% to 99%. The dose-response analysis identified an empirical threshold of approximately 6.25 g/d, equivalent to 2.5% of the EER, where dmfs began to increase most steeply, which is lower than the WHO cutoffs. These findings underscore the importance of reducing FSI to below 10% of the EER for all children and suggest a target below 5% for high-risk groups. The results offer evidence to support clinical guidance and population-level interventions to lower FSI in early childhood. Future research should test these findings in diverse sociocultural settings, including children and adults in low- and middle-income countries, to strengthen the evidence for global dietary sugar-reduction policies.
{"title":"G-Computation Quantifying Caries Reduction by World Health Organization Sugar Limits in Children.","authors":"A T M Dao,L G Do,N Stormon,H V Nguyen,D H Ha","doi":"10.1177/00220345251406559","DOIUrl":"https://doi.org/10.1177/00220345251406559","url":null,"abstract":"The World Health Organization (WHO) recommends reducing free sugar intake (FSI) to below 10%, and ideally below 5%, of the estimated energy requirement (EER) to prevent noncommunicable diseases, including dental caries. Little progress has been made in lowering FSI to reduce early childhood caries (ECC) over the past few decades. Although sugar's impact on health is well established, no studies have quantified the extent to which reducing FSI to these thresholds would reduce decayed, missing, and filled surfaces (dmfs) scores. Data from 2,182 Australian children in the SMILE birth cohort were analyzed using G-computation analysis to estimate counterfactual dmfs if FSI at age 2 y had been reduced below 10% or 5% of the EER. A dose-response analysis using restricted cubic splines was also conducted to empirically assess thresholds by modeling dmfs at age 5 y as a function of continuous FSI. The G-computation results indicate that, in the general preschool population, reducing FSI to less than 10% or 5% of the EER would result in an absolute reduction (AR) in dmfs of 1.3 and 1.5, respectively, corresponding to attributable fractions among the exposed (AFE) of 84% and 97%. Among high-risk children, the estimation impact is even greater, with ARs in dmfs of 4.4 to 4.5 and AFEs ranging from 75% to 99%. The dose-response analysis identified an empirical threshold of approximately 6.25 g/d, equivalent to 2.5% of the EER, where dmfs began to increase most steeply, which is lower than the WHO cutoffs. These findings underscore the importance of reducing FSI to below 10% of the EER for all children and suggest a target below 5% for high-risk groups. The results offer evidence to support clinical guidance and population-level interventions to lower FSI in early childhood. Future research should test these findings in diverse sociocultural settings, including children and adults in low- and middle-income countries, to strengthen the evidence for global dietary sugar-reduction policies.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"52 1","pages":"220345251406559"},"PeriodicalIF":7.6,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005334","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}
Pub Date : 2026-01-21DOI: 10.1177/00220345251385554
L Y Chen,S L Lin,J L Zhong,W L Xu,W Wen,Z D Wang,W A Xu,B L Wu,C F Zhang
Mural cells, such as pericytes, integrate with endothelial cells (ECs) lining the capillaries, which are pivotal in vascular development and stabilization as well as in supporting EC function. Dental pulp stem cells (DPSCs) were recently revealed to have intimacy with pericytes in the dental pulp microenvironment and are regulated by EphB4/ephrinB2 signaling. However, how EphB4/ephrinB2 signaling regulates DPSC pericyte biology and their interactions with ECs remains unknown. In this study, single-cell RNA sequencing data analysis and immunofluorescence staining of healthy human dental pulp were used to demonstrate the roles of mesenchymal stem cells (MSCs) as pericytes and ephrinB phosphorylation between MSCs and ECs interaction. Bulk RNA-seq further showed transcriptomic similarity between DPSCs and human brain vascular pericytes. In vitro coculture of DPSCs and ECs further confirmed ephrinB2 activation at cell-cell contact sites. To investigate how ephrinB2 influenced DPSCs' pericyte function, EFNB2 was either knocked down using small hairpin RNA or overexpressed via open reading frame (ORF) lentiviral transduction. Focal adhesion protein assessment was conducted, and a 3-dimensional (3D) fibrin beads assay was established to visualize the interaction between DPSCs and ECs in vitro. EFNB2 knockdown in DPSCs significantly reduced cell proliferation, adhesion, and transwell migration but increased contractility. Conversely, EFNB2 overexpression enhanced proliferation and adhesion but reduced migration and contractility. Interestingly, EFNB2 overexpression significantly increased ECs' sprouting capability, improving pericyte coverage in 3D fibrin beads assays. These effects were mediated through the enhanced focal adhesion pathway involving Src, paxillin and FAK phosphorylation, and vinculin. Our findings demonstrate that ephrinB2 signaling regulates critical pericyte functions of DPSCs through the Src/FAK/paxillin signaling pathway, thus modulating their adhesion toward ECs. Targeting ephrinB2 signaling may therefore represent a promising strategy to enhance vascular formation and functional recovery in dental pulp tissue engineering.
{"title":"EphrinB2 Regulates DPSC Pericyte-like Functions via the Focal Adhesion Pathway.","authors":"L Y Chen,S L Lin,J L Zhong,W L Xu,W Wen,Z D Wang,W A Xu,B L Wu,C F Zhang","doi":"10.1177/00220345251385554","DOIUrl":"https://doi.org/10.1177/00220345251385554","url":null,"abstract":"Mural cells, such as pericytes, integrate with endothelial cells (ECs) lining the capillaries, which are pivotal in vascular development and stabilization as well as in supporting EC function. Dental pulp stem cells (DPSCs) were recently revealed to have intimacy with pericytes in the dental pulp microenvironment and are regulated by EphB4/ephrinB2 signaling. However, how EphB4/ephrinB2 signaling regulates DPSC pericyte biology and their interactions with ECs remains unknown. In this study, single-cell RNA sequencing data analysis and immunofluorescence staining of healthy human dental pulp were used to demonstrate the roles of mesenchymal stem cells (MSCs) as pericytes and ephrinB phosphorylation between MSCs and ECs interaction. Bulk RNA-seq further showed transcriptomic similarity between DPSCs and human brain vascular pericytes. In vitro coculture of DPSCs and ECs further confirmed ephrinB2 activation at cell-cell contact sites. To investigate how ephrinB2 influenced DPSCs' pericyte function, EFNB2 was either knocked down using small hairpin RNA or overexpressed via open reading frame (ORF) lentiviral transduction. Focal adhesion protein assessment was conducted, and a 3-dimensional (3D) fibrin beads assay was established to visualize the interaction between DPSCs and ECs in vitro. EFNB2 knockdown in DPSCs significantly reduced cell proliferation, adhesion, and transwell migration but increased contractility. Conversely, EFNB2 overexpression enhanced proliferation and adhesion but reduced migration and contractility. Interestingly, EFNB2 overexpression significantly increased ECs' sprouting capability, improving pericyte coverage in 3D fibrin beads assays. These effects were mediated through the enhanced focal adhesion pathway involving Src, paxillin and FAK phosphorylation, and vinculin. Our findings demonstrate that ephrinB2 signaling regulates critical pericyte functions of DPSCs through the Src/FAK/paxillin signaling pathway, thus modulating their adhesion toward ECs. Targeting ephrinB2 signaling may therefore represent a promising strategy to enhance vascular formation and functional recovery in dental pulp tissue engineering.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"30 1","pages":"220345251385554"},"PeriodicalIF":7.6,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005336","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}
Pub Date : 2025-12-19DOI: 10.1177/00220345251401861
A L Campos,H S Vilela,R B Trinca,V G de Araújo Neto,E T de Sousa,V E Arana-Chavez,M Giannini,S Habelitz,R R Braga
This study investigated the efficacy of the polymer-induced liquid precursor (PILP) process and of an experimental composite containing dicalcium phosphate dihydrate (DCPD) particles for in vitro remineralization of artificial dentin lesions. The hypothesis was that pretreatment with the PILP solution associated with an external Ca2+/PO43- source represented by the composite containing DCPD would increase dentin remineralization in comparison to each strategy alone. Dentin discs with a 2.5-mm × 2.5-mm demineralized window (acetic acid, pH 5, for 66 h) were assigned to one of four experimental conditions, defined by the pretreatment (20 μL for 20 s: PILP solution or deionized water) and by the composite placed on the dentin surface: "control" (50% barium glass, BG) or "DCPD" (40% DCPD and 10% BG). Specimens were placed in artificial pulp chambers with the lower compartment filled with simulated body fluid for 28 d. Remineralization was assessed by changes in the mineral-to-matrix ratio (MMR) at the dentin-composite interface (attenuated total reflection-Fourier transform infrared spectroscopy) and by nanoindentation. Data were analyzed by repeated-measures 2-way analysis of variance/Tukey test (α = 0.05). Selected specimens were observed under scanning electron microscopy/energy-dispersive X-ray spectroscopy (EDS) and transmission electron microscopy with selected area electron diffraction analysis (SAED). All groups recovered MMR to levels similar to sound dentin, but only PILP + DCPD reached MMR levels similar to sound dentin after 14 d (P > 0.05). At the external lesion (0-90 µm), both DCPD and PILP + DCPD groups showed an elastic modulus (EM) statistically higher than the control, but only PILP + DCPD showed EM similar to sound dentin at the internal lesion (90-160 µm, P < 0.001). In relation to sound dentin, EM recovery reached 18% in the PILP group (not different from the control), 31% in the DCPD group, and 57% in the PILP + DCPD group. Micro- and ultramorphological analyses confirmed the increase in mineral content in the latter 2 groups. In conclusion, the association of both remineralization strategies improved dentin remineralization compared to either approach separately.
{"title":"Dentin Remineralization Associating Peptide- and Particle-Assisted Strategies.","authors":"A L Campos,H S Vilela,R B Trinca,V G de Araújo Neto,E T de Sousa,V E Arana-Chavez,M Giannini,S Habelitz,R R Braga","doi":"10.1177/00220345251401861","DOIUrl":"https://doi.org/10.1177/00220345251401861","url":null,"abstract":"This study investigated the efficacy of the polymer-induced liquid precursor (PILP) process and of an experimental composite containing dicalcium phosphate dihydrate (DCPD) particles for in vitro remineralization of artificial dentin lesions. The hypothesis was that pretreatment with the PILP solution associated with an external Ca2+/PO43- source represented by the composite containing DCPD would increase dentin remineralization in comparison to each strategy alone. Dentin discs with a 2.5-mm × 2.5-mm demineralized window (acetic acid, pH 5, for 66 h) were assigned to one of four experimental conditions, defined by the pretreatment (20 μL for 20 s: PILP solution or deionized water) and by the composite placed on the dentin surface: \"control\" (50% barium glass, BG) or \"DCPD\" (40% DCPD and 10% BG). Specimens were placed in artificial pulp chambers with the lower compartment filled with simulated body fluid for 28 d. Remineralization was assessed by changes in the mineral-to-matrix ratio (MMR) at the dentin-composite interface (attenuated total reflection-Fourier transform infrared spectroscopy) and by nanoindentation. Data were analyzed by repeated-measures 2-way analysis of variance/Tukey test (α = 0.05). Selected specimens were observed under scanning electron microscopy/energy-dispersive X-ray spectroscopy (EDS) and transmission electron microscopy with selected area electron diffraction analysis (SAED). All groups recovered MMR to levels similar to sound dentin, but only PILP + DCPD reached MMR levels similar to sound dentin after 14 d (P > 0.05). At the external lesion (0-90 µm), both DCPD and PILP + DCPD groups showed an elastic modulus (EM) statistically higher than the control, but only PILP + DCPD showed EM similar to sound dentin at the internal lesion (90-160 µm, P < 0.001). In relation to sound dentin, EM recovery reached 18% in the PILP group (not different from the control), 31% in the DCPD group, and 57% in the PILP + DCPD group. Micro- and ultramorphological analyses confirmed the increase in mineral content in the latter 2 groups. In conclusion, the association of both remineralization strategies improved dentin remineralization compared to either approach separately.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"50 1","pages":"220345251401861"},"PeriodicalIF":7.6,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785820","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}
Pub Date : 2025-12-18DOI: 10.1177/00220345251399558
E. Demir, I. İlgenli, Z. Guney, S. Mohammadi, K. Lauwens, N. Yakar, C. Alvarez Rivas, O. Unlu, A. Kantarci
Chronic apical periodontitis (CAP) is a persistent inflammatory condition caused by microbial infections in the root canal system, leading to bone loss and tissue damage. In this study, we tested the hypothesis that maresin 1 (MaR1), a specialized proresolving mediator, facilitates inflammatory resolution and promotes bone healing in CAP. We developed a CAP model in mice through pulp exposure. Animals received intracanal administration of either MaR1 or a vehicle. Micro–computed tomography (micro-CT) was used to analyze lesion size and bone volume changes. Inflammatory cell infiltration was assessed in hematoxylin and eosin–stained sections, and microbial diversity was analyzed using next-generation sequencing. The role of regulatory T cells (Tregs) was further explored through diphtheria toxin–induced depletion of Tregs in Foxp3eGFP/IL17 transgenic mice. All statistical analyses were performed using parametric methods, as confirmed by the Shapiro–Wilk test for data normality. Analysis of variance with Tukey’s post hoc and Bonferroni-corrected t tests was applied. P < 0.05 was considered significant. In 2-dimensional analyses, a significant difference was observed between the control and lesion groups, supporting the validity of the experimental model. MaR1 treatment significantly reduced lesion size ( P < 0.0001). The bone volume/total volume ratio was significantly higher in the MaR1 group than in the vehicle group ( P < 0.05). Bone mass was reduced in the lesion group, whereas MaR1 treatment significantly alleviated this loss ( P < 0.05). The number of inflammatory cells was significantly lower in the MaR1 group compared to the vehicle group ( P < 0.05). MaR1 also reduced Enterococcus faecalis , a key pathogen in persistent infections. This study highlights MaR1 as a promising treatment for chronic apical periodontitis, showing benefits in resolving inflammation, preserving bone, and reducing E. faecalis . Unlike conventional therapies, MaR1 supports immune modulation and tissue repair.
{"title":"Maresin 1 Resolves Inflammation and Aids Bone Healing in Periapical Lesions","authors":"E. Demir, I. İlgenli, Z. Guney, S. Mohammadi, K. Lauwens, N. Yakar, C. Alvarez Rivas, O. Unlu, A. Kantarci","doi":"10.1177/00220345251399558","DOIUrl":"https://doi.org/10.1177/00220345251399558","url":null,"abstract":"Chronic apical periodontitis (CAP) is a persistent inflammatory condition caused by microbial infections in the root canal system, leading to bone loss and tissue damage. In this study, we tested the hypothesis that maresin 1 (MaR1), a specialized proresolving mediator, facilitates inflammatory resolution and promotes bone healing in CAP. We developed a CAP model in mice through pulp exposure. Animals received intracanal administration of either MaR1 or a vehicle. Micro–computed tomography (micro-CT) was used to analyze lesion size and bone volume changes. Inflammatory cell infiltration was assessed in hematoxylin and eosin–stained sections, and microbial diversity was analyzed using next-generation sequencing. The role of regulatory T cells (Tregs) was further explored through diphtheria toxin–induced depletion of Tregs in Foxp3eGFP/IL17 transgenic mice. All statistical analyses were performed using parametric methods, as confirmed by the Shapiro–Wilk test for data normality. Analysis of variance with Tukey’s post hoc and Bonferroni-corrected <jats:italic toggle=\"yes\">t</jats:italic> tests was applied. <jats:italic toggle=\"yes\">P</jats:italic> < 0.05 was considered significant. In 2-dimensional analyses, a significant difference was observed between the control and lesion groups, supporting the validity of the experimental model. MaR1 treatment significantly reduced lesion size ( <jats:italic toggle=\"yes\">P</jats:italic> < 0.0001). The bone volume/total volume ratio was significantly higher in the MaR1 group than in the vehicle group ( <jats:italic toggle=\"yes\">P</jats:italic> < 0.05). Bone mass was reduced in the lesion group, whereas MaR1 treatment significantly alleviated this loss ( <jats:italic toggle=\"yes\">P</jats:italic> < 0.05). The number of inflammatory cells was significantly lower in the MaR1 group compared to the vehicle group ( <jats:italic toggle=\"yes\">P</jats:italic> < 0.05). MaR1 also reduced <jats:italic toggle=\"yes\">Enterococcus faecalis</jats:italic> , a key pathogen in persistent infections. This study highlights MaR1 as a promising treatment for chronic apical periodontitis, showing benefits in resolving inflammation, preserving bone, and reducing <jats:italic toggle=\"yes\">E. faecalis</jats:italic> . Unlike conventional therapies, MaR1 supports immune modulation and tissue repair.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"111 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770728","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}
Pub Date : 2025-12-18DOI: 10.1177/00220345251399645
F.V. Bitencourt, A. Trullenque-Eriksson, A. Andersen, M.V. Vettore, C. Tomasi, T. Berglundh, J. Derks
Complete edentulism represents the endpoint of oral diseases and can impair quality of life. Although diabetes is linked to oral inflammation, less is known about its relationship with complete edentulism, particularly by diabetes type. This cross-sectional study examined associations between type 1 and type 2 diabetes and complete edentulism using datasets from Denmark and Sweden and assessed whether socioeconomic status modified these associations. A total of 557,316 adults aged 18 to 75 y were included. Complete edentulism was assessed via clinical examination (register data, Sweden) or self-reporting (survey, Denmark). Diabetes was classified using validated register-based definitions. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for complete edentulism by diabetes type, adjusting for potential confounders. Age-stratified prevalence and effect modification by income and education, using additive and multiplicative scales, were examined. Complete edentulism was more prevalent among individuals with type 2 diabetes (Denmark: 4.3%, 95% CI: 4.1 to 4.6; Sweden: 1.7%, 95% CI: 1.5 to 1.7) than among those with type 1 diabetes (Denmark: 2.1%, 95% CI: 1.6 to 2.7; Sweden: 0.7%, 95% CI: 0.6 to 0.8) and without diabetes (Denmark: 1.9%, 95% CI: 1.7 to 2.0; Sweden: 0.7%, 95% CI: 0.6 to 0.7). Adjusted models showed higher odds of complete edentulism in type 1 diabetes (Denmark: OR 1.77, 95% CI 1.31 to 2.39; Sweden: OR 1.27, 95% CI 1.07 to 1.50) and type 2 diabetes (Denmark: OR 1.89, 95% CI 1.68 to 2.12; Sweden: OR 1.73, 95% CI 1.63 to 1.84). Effect modification analyses revealed a consistent direction of association, with an additive effect of lower income and educational attainment, as indicated by positive relative excess risk due to interaction estimates (Denmark: 0.96 to 2.31; Sweden: 0.26 to 1.83). In conclusion, diabetes types 1 and 2 were associated with complete edentulism, especially among socioeconomically disadvantaged groups.
全牙补牙是口腔疾病的终点，也会影响生活质量。虽然糖尿病与口腔炎症有关，但人们对其与全牙症的关系知之甚少，特别是糖尿病类型。这项横断面研究使用来自丹麦和瑞典的数据集检查了1型和2型糖尿病与全牙化之间的关联，并评估了社会经济地位是否改变了这些关联。共有557,316名18至75岁的成年人被纳入研究。通过临床检查（登记数据，瑞典）或自我报告（调查，丹麦）评估全牙补牙情况。使用基于注册表的有效定义对糖尿病进行分类。采用Logistic回归来估计糖尿病类型的全牙义齿的优势比（ORs）和95%置信区间（ci），并对潜在的混杂因素进行调整。采用加性和乘性量表，对收入和教育对年龄分层患病率和效果的影响进行了研究。2型糖尿病患者（丹麦：4.3%,95% CI: 4.1至4.6；瑞典：1.7%,95% CI: 1.5至1.7）比1型糖尿病患者（丹麦：2.1%,95% CI: 1.6至2.7；瑞典：0.7%,95% CI: 0.6至0.8）和无糖尿病患者（丹麦：1.9%,95% CI: 1.7至2.0；瑞典：0.7%,95% CI: 0.6至0.7）更普遍。调整后的模型显示，1型糖尿病（丹麦：OR 1.77, 95% CI 1.31至2.39；瑞典：OR 1.27, 95% CI 1.07至1.50）和2型糖尿病（丹麦：OR 1.89, 95% CI 1.68至2.12；瑞典：OR 1.73, 95% CI 1.63至1.84）患者患全牙基牙的几率更高。效应修正分析揭示了一个一致的关联方向，即低收入和受教育程度的加性效应，正如由于相互作用估计而产生的正相对超额风险所表明的那样（丹麦：0.96至2.31；瑞典：0.26至1.83）。总之，1型和2型糖尿病与全牙缺牙症有关，特别是在社会经济条件较差的人群中。
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Pub Date : 2025-12-18DOI: 10.1177/00220345251397858
B. Liu, F. Hermans, F. Aellos, J. Dworan, E. Chang, A. Clavelier, N. Ranjith, S.A. Millan, M.M. Torabi, I. Lambrichts, J.A. Helms
Once considered vestigial structures, epithelial rests of Malassez (ERMs) have recently been implicated in periodontal repair, largely based on their location in the periodontal ligament space, adjacent to damaged tissues. This study decodes what ERM activation entails and then tests in a variety of periodontal injury models the consequences of injury activation on ERM behavior and function. A Wnt lineage tracer strain Axin2CreERT2/+ ; R26RmTmG/+ was employed to map the distribution of Wnt-responsive cells and their descendants during root development and in response to injuries to the periodontium. Injury-activated murine ERMs were compared against developmental ERMs, and both were analyzed by histology and immunohistochemistry (IHC). Additionally, ERMs isolated from human tissues were analyzed by single-cell RNA sequencing and IHC. During root development, ERMs were surrounded by Wnt-responsive cells and their progeny. In response to injury, both the number and size of ERMs significantly increased, and this injury-induced enlargement did not involve cell proliferation. The injury-activated state of ERMs was accompanied by expression of Wnt pathway components. Compared to ERMs in uninjured tissues, injury-activated ERMs exhibited a shift toward expression of molecular markers associated with the epithelial-to-mesenchymal transition (EMT). When ERMs were juxtaposed to an injured junctional epithelium (JE) or damaged cementum, some ERM cells adopted a stellate morphology, exhibited evidence of matrix remodeling, and showed a loss of cell–cell adhesion, contributing to the repair of cementum and the JE. A dynamic state of Wnt responsiveness exists in injury-activated ERMs, and a subset of ERM cells undergo EMT. Together, these findings raise the possibility that cells in and around these activated ERMs may adopt an active role in periodontal repair.
{"title":"Injury-Activated ERMs Undergo EMT and May Contribute to Periodontal Repair","authors":"B. Liu, F. Hermans, F. Aellos, J. Dworan, E. Chang, A. Clavelier, N. Ranjith, S.A. Millan, M.M. Torabi, I. Lambrichts, J.A. Helms","doi":"10.1177/00220345251397858","DOIUrl":"https://doi.org/10.1177/00220345251397858","url":null,"abstract":"Once considered vestigial structures, epithelial rests of Malassez (ERMs) have recently been implicated in periodontal repair, largely based on their location in the periodontal ligament space, adjacent to damaged tissues. This study decodes what ERM activation entails and then tests in a variety of periodontal injury models the consequences of injury activation on ERM behavior and function. A Wnt lineage tracer strain <jats:italic toggle=\"yes\">Axin2Cre</jats:italic> <jats:sup>ERT2/+</jats:sup> ; <jats:italic toggle=\"yes\">R26R</jats:italic> <jats:sup>mTmG/+</jats:sup> was employed to map the distribution of Wnt-responsive cells and their descendants during root development and in response to injuries to the periodontium. Injury-activated murine ERMs were compared against developmental ERMs, and both were analyzed by histology and immunohistochemistry (IHC). Additionally, ERMs isolated from human tissues were analyzed by single-cell RNA sequencing and IHC. During root development, ERMs were surrounded by Wnt-responsive cells and their progeny. In response to injury, both the number and size of ERMs significantly increased, and this injury-induced enlargement did not involve cell proliferation. The injury-activated state of ERMs was accompanied by expression of Wnt pathway components. Compared to ERMs in uninjured tissues, injury-activated ERMs exhibited a shift toward expression of molecular markers associated with the epithelial-to-mesenchymal transition (EMT). When ERMs were juxtaposed to an injured junctional epithelium (JE) or damaged cementum, some ERM cells adopted a stellate morphology, exhibited evidence of matrix remodeling, and showed a loss of cell–cell adhesion, contributing to the repair of cementum and the JE. A dynamic state of Wnt responsiveness exists in injury-activated ERMs, and a subset of ERM cells undergo EMT. Together, these findings raise the possibility that cells in and around these activated ERMs may adopt an active role in periodontal repair.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"15 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770749","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}
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