Pub Date : 2026-02-24DOI: 10.1177/00220345261417597
R. Miyazaki, H. Kawasaki, H. Kato, I. Ohta, R. Ishikawa, K. Yoshimura, H. Yamada, Y. Sakai, H. Suzuki, M. Sugita, Y. Watanabe, K. Masumoto, K. Shinmura
Ameloblastoma (AB) is a benign yet locally aggressive odontogenic epithelial tumor, characterized by frequent recurrence and a potential for distant metastasis. The primary cilium (PC), a microtubule-based organelle that serves as a signaling hub for multiple oncogenic pathways, is typically reduced or absent in most human malignancies; however, its status in AB remains poorly defined. In this retrospective, tissue-based observational study, we investigated the presence of PC in 42 AB cases, encompassing all major histological subtypes, using immunohistochemistry, immunofluorescence, and ultrastructural techniques. As a comparator, 41 cases of oral squamous cell carcinoma (OSCC), a tumor originating from the same oral cavity region, were also analyzed. PC were consistently detected in all ABs but were absent in OSCCs. In ABs, the presence of PC was validated by multiple markers and imaging modalities. In conventional AB, the density of PC varies significantly among the histological patterns. Notably, the cilia frequently exhibited a polarized orientation in the peripheral columnar cells of the follicular subtype. PC were also present in recurrent and metastatic lesions, although their significance in disease progression remains uncertain. Elevated GLI1 mRNA expression, nuclear accumulation of GLI1, and elevated SHH mRNA and protein expression indicated the activation of the Hh signaling pathway in ABs. Transcriptomic screening of early ciliogenesis-related genes revealed selective upregulation of CEP164 in ABs but not in OSCCs or other PC-deficient carcinomas. CEP164 protein was significantly overexpressed and localized closely apposed to but only partially overlapped with γ-tubulin signals, consistent with its role at the distal appendages of the basal body. Functional analyses demonstrated that CEP164 overexpression promoted PC formation, whereas its knockdown suppressed ciliogenesis. These findings indicate that ABs uniquely preserve functional PC and implicate CEP164 as a key mediator of this phenotype, offering novel insights into AB biology and highlighting its potential as a diagnostic and therapeutic target.
{"title":"Ameloblastoma Displays Primary Cilia Maintenance and CEP164 Overexpression","authors":"R. Miyazaki, H. Kawasaki, H. Kato, I. Ohta, R. Ishikawa, K. Yoshimura, H. Yamada, Y. Sakai, H. Suzuki, M. Sugita, Y. Watanabe, K. Masumoto, K. Shinmura","doi":"10.1177/00220345261417597","DOIUrl":"https://doi.org/10.1177/00220345261417597","url":null,"abstract":"Ameloblastoma (AB) is a benign yet locally aggressive odontogenic epithelial tumor, characterized by frequent recurrence and a potential for distant metastasis. The primary cilium (PC), a microtubule-based organelle that serves as a signaling hub for multiple oncogenic pathways, is typically reduced or absent in most human malignancies; however, its status in AB remains poorly defined. In this retrospective, tissue-based observational study, we investigated the presence of PC in 42 AB cases, encompassing all major histological subtypes, using immunohistochemistry, immunofluorescence, and ultrastructural techniques. As a comparator, 41 cases of oral squamous cell carcinoma (OSCC), a tumor originating from the same oral cavity region, were also analyzed. PC were consistently detected in all ABs but were absent in OSCCs. In ABs, the presence of PC was validated by multiple markers and imaging modalities. In conventional AB, the density of PC varies significantly among the histological patterns. Notably, the cilia frequently exhibited a polarized orientation in the peripheral columnar cells of the follicular subtype. PC were also present in recurrent and metastatic lesions, although their significance in disease progression remains uncertain. Elevated GLI1 mRNA expression, nuclear accumulation of GLI1, and elevated SHH mRNA and protein expression indicated the activation of the Hh signaling pathway in ABs. Transcriptomic screening of early ciliogenesis-related genes revealed selective upregulation of CEP164 in ABs but not in OSCCs or other PC-deficient carcinomas. CEP164 protein was significantly overexpressed and localized closely apposed to but only partially overlapped with γ-tubulin signals, consistent with its role at the distal appendages of the basal body. Functional analyses demonstrated that CEP164 overexpression promoted PC formation, whereas its knockdown suppressed ciliogenesis. These findings indicate that ABs uniquely preserve functional PC and implicate CEP164 as a key mediator of this phenotype, offering novel insights into AB biology and highlighting its potential as a diagnostic and therapeutic target.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"97 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147274340","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 : 2026-02-24DOI: 10.1177/00220345261417246
C. Leiva-Sabadini, C.M. Lévesque, L. Bozec, C. Schuh, S. Aguayo
Dental caries remains a globally prevalent disease, driven by microbial dysbiosis and competitive ecological shifts within the oral biofilm. A key interaction in this context is the antagonism between Streptococcus mutans and Streptococcus sanguinis , two early colonizers of the dentin surfaces. While bacterial extracellular vesicles (bEVs) have emerged as important mediators of microbial communication, their role in interspecies adhesion and early biofilm dynamics remains poorly understood. This study explored how S. mutans –derived bEVs, isolated from planktonic cultures and biofilms grown on native or glycated type I collagen substrates, modulate S. sanguinis nanoadhesion and initial biofilm formation. Bacterial EVs were characterized using nanoparticle tracking analysis and transmission electron microscopy, and their functional effects were assessed via atomic force microscopy–based single-cell force spectroscopy. This approach enabled direct quantification of bacterial adhesion forces and single-molecule unbinding events under different vesicle-exposure conditions. Our results demonstrated that planktonic-derived bEVs enhanced S. sanguinis adhesion at 5-s contact times, while bEVs from collagen-bound S. mutans biofilms, particularly those grown on glycated matrices, consistently reduced adhesion forces, rupture lengths, and unbinding events. Optical coherence tomography imaging confirmed that these nanoscale effects translated into altered early biofilm architecture, with planktonic bEVs promoting thicker, denser biofilms and biofilm-derived bEVs leading to sparser colonization. Our findings suggest that S. mutans bEVs exhibit a context-dependent modulatory effect on S. sanguinis , enhancing adhesion under planktonic conditions and suppressing it upon biofilm establishment. This biphasic behavior may represent a strategic mechanism for niche domination during caries initiation. Moreover, collagen glycation—mimicking aged or hyperglycemic dentin—further influenced bEV function, underscoring the importance of the host matrix state in microbial interactions. Overall, this study highlights a previously unrecognized role for bEVs in shaping early oral dysbiosis at the single-cell level.
{"title":"Streptococcus mutans Extracellular Vesicles Regulate Early Streptococcus sanguinis Nanoadhesion","authors":"C. Leiva-Sabadini, C.M. Lévesque, L. Bozec, C. Schuh, S. Aguayo","doi":"10.1177/00220345261417246","DOIUrl":"https://doi.org/10.1177/00220345261417246","url":null,"abstract":"Dental caries remains a globally prevalent disease, driven by microbial dysbiosis and competitive ecological shifts within the oral biofilm. A key interaction in this context is the antagonism between <jats:italic toggle=\"yes\">Streptococcus mutans</jats:italic> and <jats:italic toggle=\"yes\">Streptococcus sanguinis</jats:italic> , two early colonizers of the dentin surfaces. While bacterial extracellular vesicles (bEVs) have emerged as important mediators of microbial communication, their role in interspecies adhesion and early biofilm dynamics remains poorly understood. This study explored how <jats:italic toggle=\"yes\">S. mutans</jats:italic> –derived bEVs, isolated from planktonic cultures and biofilms grown on native or glycated type I collagen substrates, modulate <jats:italic toggle=\"yes\">S. sanguinis</jats:italic> nanoadhesion and initial biofilm formation. Bacterial EVs were characterized using nanoparticle tracking analysis and transmission electron microscopy, and their functional effects were assessed via atomic force microscopy–based single-cell force spectroscopy. This approach enabled direct quantification of bacterial adhesion forces and single-molecule unbinding events under different vesicle-exposure conditions. Our results demonstrated that planktonic-derived bEVs enhanced <jats:italic toggle=\"yes\">S. sanguinis</jats:italic> adhesion at 5-s contact times, while bEVs from collagen-bound <jats:italic toggle=\"yes\">S. mutans</jats:italic> biofilms, particularly those grown on glycated matrices, consistently reduced adhesion forces, rupture lengths, and unbinding events. Optical coherence tomography imaging confirmed that these nanoscale effects translated into altered early biofilm architecture, with planktonic bEVs promoting thicker, denser biofilms and biofilm-derived bEVs leading to sparser colonization. Our findings suggest that <jats:italic toggle=\"yes\">S. mutans</jats:italic> bEVs exhibit a context-dependent modulatory effect on <jats:italic toggle=\"yes\">S. sanguinis</jats:italic> , enhancing adhesion under planktonic conditions and suppressing it upon biofilm establishment. This biphasic behavior may represent a strategic mechanism for niche domination during caries initiation. Moreover, collagen glycation—mimicking aged or hyperglycemic dentin—further influenced bEV function, underscoring the importance of the host matrix state in microbial interactions. Overall, this study highlights a previously unrecognized role for bEVs in shaping early oral dysbiosis at the single-cell level.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"14 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147274326","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}
Saliva secretion requires continuous energy supply throughout the day. Mitochondria dynamically adapt to fluctuating energy demands, yet the mechanisms underlying the adaptions remain poorly understood. Here, we employed real-time intravital imaging and fluorescence lifetime imaging microscopy (FLIM) to monitor mitochondria functions in submandibular glands. We revealed distinct mitochondrial distribution patterns; in acinar cells, mitochondria were predominantly distributed near the cell membranes or scattered throughout the cytoplasm with extensive endoplasmic reticulum (ER)–mitochondria contact sites, whereas in ductal cells, mitochondria were densely packed within the cytoplasm. At resting states, mitochondria exhibited larger volumes, fewer numbers, and higher oxidative phosphorylation activity in acinar cells compared with those in ductal cells. Upon stimulation with pilocarpine, mitochondrial motility, NAD(P)H levels, NAD(P)H enzyme–bound fractions, and mitochondrial adenosine triphosphate (ATP) production were significantly elevated. Pilocarpine-induced secretion, mediated by both aquaporin 5 translocation and the opening of paracellular pathway, was markedly attenuated by oligomycin A, an ATP synthase inhibitor. Notably, pilocarpine increased mitochondria–ER contact sites to 1.7 times the control level (from 18% to 31%), and blocking mitochondrial calcium uptake significantly suppressed pilocarpine-induced NAD(P)H and ATP production. These findings highlight the critical role of ER–mitochondria calcium transfer in sustaining bioenergetics required for salivary secretion, providing new insights into mitochondrial functional adaptation and its physiological significance in intact secretory systems.
{"title":"Endoplasmic Reticulum–Mitochondria Calcium Drives Salivary Bioenergetics","authors":"S.N. Min, X.D. Mao, J.Z. Su, L.L. Wu, G.Y. Yu, X. Cong","doi":"10.1177/00220345251411909","DOIUrl":"https://doi.org/10.1177/00220345251411909","url":null,"abstract":"Saliva secretion requires continuous energy supply throughout the day. Mitochondria dynamically adapt to fluctuating energy demands, yet the mechanisms underlying the adaptions remain poorly understood. Here, we employed real-time intravital imaging and fluorescence lifetime imaging microscopy (FLIM) to monitor mitochondria functions in submandibular glands. We revealed distinct mitochondrial distribution patterns; in acinar cells, mitochondria were predominantly distributed near the cell membranes or scattered throughout the cytoplasm with extensive endoplasmic reticulum (ER)–mitochondria contact sites, whereas in ductal cells, mitochondria were densely packed within the cytoplasm. At resting states, mitochondria exhibited larger volumes, fewer numbers, and higher oxidative phosphorylation activity in acinar cells compared with those in ductal cells. Upon stimulation with pilocarpine, mitochondrial motility, NAD(P)H levels, NAD(P)H enzyme–bound fractions, and mitochondrial adenosine triphosphate (ATP) production were significantly elevated. Pilocarpine-induced secretion, mediated by both aquaporin 5 translocation and the opening of paracellular pathway, was markedly attenuated by oligomycin A, an ATP synthase inhibitor. Notably, pilocarpine increased mitochondria–ER contact sites to 1.7 times the control level (from 18% to 31%), and blocking mitochondrial calcium uptake significantly suppressed pilocarpine-induced NAD(P)H and ATP production. These findings highlight the critical role of ER–mitochondria calcium transfer in sustaining bioenergetics required for salivary secretion, providing new insights into mitochondrial functional adaptation and its physiological significance in intact secretory systems.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"15 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147274333","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}
Oral diseases remain a pressing global health challenge, affecting billions and disproportionately affecting underserved and vulnerable populations. Despite strong evidence supporting preventive measures, this evidence often fails to translate into real-world practice due to fragmented health systems, a treatment-dominated model of dental care, and a lack of focus on upstream, population-wide prevention strategies. Implementation research helps to bridge the effectiveness-implementation gap by systematically studying how interventions can be integrated into real-world settings and sustained effectively. Implementation research requires a multidisciplinary approach that often goes beyond traditional research settings, prioritizing stakeholder engagement, local context, and iterative testing and aligning interventions with community needs. To support the design and evaluation of these implementation efforts, logic models are practical tools that can be used to help map determinants, strategies, and outcomes using underlying causal reasoning. Once determinants have been identified, trials can be developed to incorporate implementation outcomes such as acceptability (how agreeable it is among stakeholders), adoption (the uptake), and fidelity (how closely implemented as intended), providing insights into the real-world performance of interventions. Implementation strategies should be clearly defined and documented by detailing their rationale, specific actions, and outcomes they are intended to affect. Specifying and contextualizing strategies in this way ensures they can be appropriately evaluated. This article identifies 3 examples that show the importance of embedding interventions within existing health systems and policies and how bottom-up approaches, such as engaging stakeholders from the outset, are critical to the success of the implementation. Integrating implementation considerations early in the research process and fostering strategic partnerships between research organizations, policymakers, and communities are essential to translating evidence into meaningful oral health improvements and bridging the gap between research and real-world impact.
{"title":"Implementation Research Is Underdeveloped in Oral Health: Bridging the Gap","authors":"J.R.H. Tay, H.B. Bosworth, C.H. Fox, J.E. Gallagher, N.S. Jakubovics, F. Schwendicke, G.G. Nascimento","doi":"10.1177/00220345251410462","DOIUrl":"https://doi.org/10.1177/00220345251410462","url":null,"abstract":"Oral diseases remain a pressing global health challenge, affecting billions and disproportionately affecting underserved and vulnerable populations. Despite strong evidence supporting preventive measures, this evidence often fails to translate into real-world practice due to fragmented health systems, a treatment-dominated model of dental care, and a lack of focus on upstream, population-wide prevention strategies. Implementation research helps to bridge the effectiveness-implementation gap by systematically studying how interventions can be integrated into real-world settings and sustained effectively. Implementation research requires a multidisciplinary approach that often goes beyond traditional research settings, prioritizing stakeholder engagement, local context, and iterative testing and aligning interventions with community needs. To support the design and evaluation of these implementation efforts, logic models are practical tools that can be used to help map determinants, strategies, and outcomes using underlying causal reasoning. Once determinants have been identified, trials can be developed to incorporate implementation outcomes such as acceptability (how agreeable it is among stakeholders), adoption (the uptake), and fidelity (how closely implemented as intended), providing insights into the real-world performance of interventions. Implementation strategies should be clearly defined and documented by detailing their rationale, specific actions, and outcomes they are intended to affect. Specifying and contextualizing strategies in this way ensures they can be appropriately evaluated. This article identifies 3 examples that show the importance of embedding interventions within existing health systems and policies and how bottom-up approaches, such as engaging stakeholders from the outset, are critical to the success of the implementation. Integrating implementation considerations early in the research process and fostering strategic partnerships between research organizations, policymakers, and communities are essential to translating evidence into meaningful oral health improvements and bridging the gap between research and real-world impact.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"4 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215580","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 : 2026-02-18DOI: 10.1177/00220345261417685
R. Ridout, R. Ahmad, A. Smith
{"title":"Letter to the Editor, “Global Oral Health: Defining the Research Agenda in the Public Interest”","authors":"R. Ridout, R. Ahmad, A. Smith","doi":"10.1177/00220345261417685","DOIUrl":"https://doi.org/10.1177/00220345261417685","url":null,"abstract":"","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"37 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146210353","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 : 2026-02-12DOI: 10.1177/00220345261416408
G. Sarra, S. Parsaei, M.P. Gomes, Y.-C. Lin, A.C. Pedroni, D. Raval, D. Hu, S. Berry, R. Baron, F.B. Bidlack, F. Gori
Our studies have established that loss-of-function mutations in the Wnt signaling antagonist SFRP4 (Secreted Frizzled Related Protein 4) cause Pyle disease, a rare skeletal disease characterized by limb deformity. Pyle disease can also present with a number of dental conditions, including tooth decay and taurodontism. Aside from the sparse clinical descriptions of the tooth anomalies seen in Pyle disease, the role of Sfrp4 in teeth has not been investigated. Here we show that in adult mouse incisors, Sfrp4 is expressed in the mesenchymal and epithelial compartments and their derivatives as well in the developing apex of the molar roots, pulp, odontoblasts, and periodontal ligament. We report that Sfrp4 deletion in mice leads to markedly shorter incisors, with reduced dentin mineral apposition and enamel volume. In addition, we find that Sfrp4 deletion leads to a reduction in the root length and bifurcation height of the developing molars, both features of taurodontism. Rodent incisors grow continuously during the animal’s lifetime, thanks to the maintenance and interactions of epithelial (EpSCs) and mesenchymal stem cells (MSCs) at their apex. As such, the mouse incisor is a powerful tool for studying adult stem cells, their interactions, and their regulation. Using this model, we found that Sfrp4 deletion leads to a significant decrease in Gli1 + MSCs and in Ki67 levels in mesenchymal transient amplifying cells and preameloblasts. Sfrp4 -null incisors have reduced type I collagen levels and altered amelogenin and Mmp20 secretion accompanied by changes in the enamel maturation stages. When incisor growth is accelerated by preventing occlusion through tooth clipping, Sfrp4 -null incisors grow significantly slower than wt incisors do. Our study suggests a key role for Sfrp4 in the fast-growing teeth (incisors) and developing molars, where there is a need to balance the maintenance and differentiation of the stem cell niche.
{"title":"Sfrp4 Is Required for Proper Dental Formation and Stem Cell Regulation","authors":"G. Sarra, S. Parsaei, M.P. Gomes, Y.-C. Lin, A.C. Pedroni, D. Raval, D. Hu, S. Berry, R. Baron, F.B. Bidlack, F. Gori","doi":"10.1177/00220345261416408","DOIUrl":"https://doi.org/10.1177/00220345261416408","url":null,"abstract":"Our studies have established that loss-of-function mutations in the Wnt signaling antagonist <jats:italic toggle=\"yes\">SFRP4</jats:italic> (Secreted Frizzled Related Protein 4) cause Pyle disease, a rare skeletal disease characterized by limb deformity. Pyle disease can also present with a number of dental conditions, including tooth decay and taurodontism. Aside from the sparse clinical descriptions of the tooth anomalies seen in Pyle disease, the role of Sfrp4 in teeth has not been investigated. Here we show that in adult mouse incisors, Sfrp4 is expressed in the mesenchymal and epithelial compartments and their derivatives as well in the developing apex of the molar roots, pulp, odontoblasts, and periodontal ligament. We report that <jats:italic toggle=\"yes\">Sfrp4</jats:italic> deletion in mice leads to markedly shorter incisors, with reduced dentin mineral apposition and enamel volume. In addition, we find that <jats:italic toggle=\"yes\">Sfrp4</jats:italic> deletion leads to a reduction in the root length and bifurcation height of the developing molars, both features of taurodontism. Rodent incisors grow continuously during the animal’s lifetime, thanks to the maintenance and interactions of epithelial (EpSCs) and mesenchymal stem cells (MSCs) at their apex. As such, the mouse incisor is a powerful tool for studying adult stem cells, their interactions, and their regulation. Using this model, we found that <jats:italic toggle=\"yes\">Sfrp4</jats:italic> deletion leads to a significant decrease in Gli1 <jats:sup>+</jats:sup> MSCs and in Ki67 levels in mesenchymal transient amplifying cells and preameloblasts. <jats:italic toggle=\"yes\">Sfrp4</jats:italic> -null incisors have reduced type I collagen levels and altered amelogenin and Mmp20 secretion accompanied by changes in the enamel maturation stages. When incisor growth is accelerated by preventing occlusion through tooth clipping, <jats:italic toggle=\"yes\">Sfrp4</jats:italic> -null incisors grow significantly slower than <jats:italic toggle=\"yes\">wt</jats:italic> incisors do. Our study suggests a key role for Sfrp4 in the fast-growing teeth (incisors) and developing molars, where there is a need to balance the maintenance and differentiation of the stem cell niche.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"98 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146160509","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 : 2026-02-12DOI: 10.1177/00220345251407609
H. Dong, L. Guan, J. Zhong, F. Lai, L. Lin, M. Li, J. Zhang, B. Wang, Y. Li, Y. Huang, Y. Jiang, Q. Jiang
Bone marrow stem cells (BMSCs), dental pulp stem cells (DPSCs), and periodontal ligament stem cells (PDLSCs) represent key stem cell sources for regenerative endodontic therapy. Recent studies indicate that these 3 cell types exhibit similar mineralization potential during mineralized induction. This study aimed to compare the mineralization potential (including odontogenic and osteogenic potential) of these 3 mouse-derived cells and identify shared or related circular RNA-mediated regulatory mechanisms. In this study, we observed high expression levels of osteogenic differentiation markers alkaline phosphatase (ALP), RUNX2, and osteocalcin (OCN) in both BMSCs and PDLSCs during mineralization, while key markers for odontoblastic differentiation (DSPP and DMP-1) were significantly upregulated, specifically in DPSCs. Bioinformatics and experimental validation identified circ_015350 as consistently upregulated during mineralization. Functional studies demonstrated that circ_015350 knockdown reduced mineralization markers: ALP and OCN in BMSCs/PDLSCs, while primarily affecting DMP-1 and DSPP in DPSCs. Conversely, circ_015350 overexpression enhanced odonto/osteogenic markers across all cell types, with particularly strong DMP-1 and DSPP elevation in DPSCs. Bioinformatics analysis predicted circ_015350 interactions with 10 microRNAs and 89 RNA-binding proteins, along with involvement in Hippo, PI3K-Akt, and AMPK pathways. Our findings reveal distinct differentiation potential: BMSCs showed greater osteogenic capacity, while DPSCs displayed stronger odontogenic potential. Circ_015350 emerged as a key regulator promoting both odontogenic and osteogenic differentiation in all 3 stem cell types, with particularly pronounced effects on odontogenic differentiation. These results suggest circ_015350 as a potential therapeutic target for dental tissue regeneration, although further investigation is needed to fully elucidate its downstream regulatory mechanisms.
{"title":"Circ_015350 Mediates Odonto/osteogenic Differentiation in Different Stem Cells","authors":"H. Dong, L. Guan, J. Zhong, F. Lai, L. Lin, M. Li, J. Zhang, B. Wang, Y. Li, Y. Huang, Y. Jiang, Q. Jiang","doi":"10.1177/00220345251407609","DOIUrl":"https://doi.org/10.1177/00220345251407609","url":null,"abstract":"Bone marrow stem cells (BMSCs), dental pulp stem cells (DPSCs), and periodontal ligament stem cells (PDLSCs) represent key stem cell sources for regenerative endodontic therapy. Recent studies indicate that these 3 cell types exhibit similar mineralization potential during mineralized induction. This study aimed to compare the mineralization potential (including odontogenic and osteogenic potential) of these 3 mouse-derived cells and identify shared or related circular RNA-mediated regulatory mechanisms. In this study, we observed high expression levels of osteogenic differentiation markers alkaline phosphatase (ALP), RUNX2, and osteocalcin (OCN) in both BMSCs and PDLSCs during mineralization, while key markers for odontoblastic differentiation (DSPP and DMP-1) were significantly upregulated, specifically in DPSCs. Bioinformatics and experimental validation identified circ_015350 as consistently upregulated during mineralization. Functional studies demonstrated that circ_015350 knockdown reduced mineralization markers: ALP and OCN in BMSCs/PDLSCs, while primarily affecting DMP-1 and DSPP in DPSCs. Conversely, circ_015350 overexpression enhanced odonto/osteogenic markers across all cell types, with particularly strong DMP-1 and DSPP elevation in DPSCs. Bioinformatics analysis predicted circ_015350 interactions with 10 microRNAs and 89 RNA-binding proteins, along with involvement in Hippo, PI3K-Akt, and AMPK pathways. Our findings reveal distinct differentiation potential: BMSCs showed greater osteogenic capacity, while DPSCs displayed stronger odontogenic potential. Circ_015350 emerged as a key regulator promoting both odontogenic and osteogenic differentiation in all 3 stem cell types, with particularly pronounced effects on odontogenic differentiation. These results suggest circ_015350 as a potential therapeutic target for dental tissue regeneration, although further investigation is needed to fully elucidate its downstream regulatory mechanisms.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"91 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146160510","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 : 2026-02-12DOI: 10.1177/00220345251409777
Z. Zhao, H. Feng, X. Wang, B. Cheng, W. Zhao, X. Pei
Diabetic periodontitis constitutes a serious and multifaceted public health issue, acting as a significant risk factor for various systemic diseases by exacerbating inflammatory responses and disrupting metabolic stability. Its high prevalence, severe periodontal tissue destruction, and complex pathological mechanisms present substantial therapeutic challenges. Conventional therapies frequently fail to target underlying molecular pathological mechanisms. Ferroptosis, an iron-dependent form of regulated cell death characterized by iron accumulation and lipid peroxidation, has been increasingly implicated in diabetic periodontitis. However, translating ferroptosis inhibition into effective therapy remains problematic. Current strategies, primarily relying on single-pathway inhibitors, exhibit insufficient effectiveness. To overcome this, we engineered a bimetallic ZIF-8 codelivery nanoplatform (FGZ nanoparticles [NPs]) for sustained release of gallium ions (Ga³+) and canonical ferroptosis inhibitor ferrostatin-1 (Fer-1), synergistically integrating the functions of the 2 drugs. FGZ NPs potently activated the Nrf2/HO-1 cytoprotective pathway, simultaneously reestablishing iron homeostasis and strengthening antioxidant capacity, resulting in effective dual-pathway ferroptosis inhibition. FGZ NPs demonstrated outstanding therapeutic outcomes, significantly promoting the regeneration of damaged periodontal tissues. This study validates ferroptosis as a promising target for diabetic periodontitis and introduces a novel strategy that surpasses the constraints of single-pathway ferroptosis inhibition, providing a new design framework for biomaterials targeting ferroptosis-related diseases.
{"title":"Nano-Driven Dual Ferroptosis Inhibition for Diabetic Periodontitis Therapy","authors":"Z. Zhao, H. Feng, X. Wang, B. Cheng, W. Zhao, X. Pei","doi":"10.1177/00220345251409777","DOIUrl":"https://doi.org/10.1177/00220345251409777","url":null,"abstract":"Diabetic periodontitis constitutes a serious and multifaceted public health issue, acting as a significant risk factor for various systemic diseases by exacerbating inflammatory responses and disrupting metabolic stability. Its high prevalence, severe periodontal tissue destruction, and complex pathological mechanisms present substantial therapeutic challenges. Conventional therapies frequently fail to target underlying molecular pathological mechanisms. Ferroptosis, an iron-dependent form of regulated cell death characterized by iron accumulation and lipid peroxidation, has been increasingly implicated in diabetic periodontitis. However, translating ferroptosis inhibition into effective therapy remains problematic. Current strategies, primarily relying on single-pathway inhibitors, exhibit insufficient effectiveness. To overcome this, we engineered a bimetallic ZIF-8 codelivery nanoplatform (FGZ nanoparticles [NPs]) for sustained release of gallium ions (Ga³+) and canonical ferroptosis inhibitor ferrostatin-1 (Fer-1), synergistically integrating the functions of the 2 drugs. FGZ NPs potently activated the Nrf2/HO-1 cytoprotective pathway, simultaneously reestablishing iron homeostasis and strengthening antioxidant capacity, resulting in effective dual-pathway ferroptosis inhibition. FGZ NPs demonstrated outstanding therapeutic outcomes, significantly promoting the regeneration of damaged periodontal tissues. This study validates ferroptosis as a promising target for diabetic periodontitis and introduces a novel strategy that surpasses the constraints of single-pathway ferroptosis inhibition, providing a new design framework for biomaterials targeting ferroptosis-related diseases.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"162 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146160513","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 : 2026-02-12DOI: 10.1177/00220345251407594
Y. Zhang, W. Wu, J. Sun, X. Chen, J. Zhang, Z. Chen
Tooth replantation is a clinical treatment commonly used for refractory periapical periodontitis, tooth avulsion, and autotransplantation. The condition of the periodontal ligament (PDL) is a prognostic factor that affects replantation outcomes. Various studies have been devoted to improving the repair of the PDL after replantation to improve the prognosis. Prostaglandin E2 (PGE2), an inflammatory mediator with critical effects involved in stem cell regulation as well as in tissue repair and regeneration, has been found to be increased after replantation. Thus, we hypothesized that the increased PGE2 in the PDL microenvironment may influence the viability of the PDL stem cells to affect PDL repair and improve replantation outcomes. We established a mouse model and found increased cyclooxygenase-2 expression and PGE2 concentrations within 1 to 3 d postreplantation. Human PDL stem cells (hPDLSCs) were stimulated with PGE2 and an EP4 agonist (L-902688) to assess viability, apoptosis, and cell cycle. Ribonucleic acid sequencing was performed to explore downstream mechanisms. The reanalysis of single-cell ribonucleic acid sequencing data suggested EP4 was the principal effective PGE2 receptor. PGE2 and EP4 agonist treatment enhanced the proliferation and viability of hPDLSCs. Ribonucleic acid sequencing identified transcriptional and immune response regulator (TCIM), a positive regulator of the Wnt/β-catenin signaling pathway, as a key downstream target. Knockdown of TCIM abrogated the proliferative effects of PGE2. In a mouse intervention model, the administration of SW033291 (a 15-hydroxyprostaglandin dehydrogenase inhibitor) or L-902688 significantly improved outcomes and increased TCIM expression in vivo. Our study demonstrates that PGE2 transiently increases in the PDL following replantation and enhances the proliferative capacity of hPDLSCs via EP4 activation, leading to the upregulation of TCIM and Wnt pathway activation. These findings offer mechanistic insight into periodontal repair and support the development of pharmaceutical strategies to improve replantation outcomes.
{"title":"PGE2 Regulates Periodontal Ligament Repair after Tooth Replantation","authors":"Y. Zhang, W. Wu, J. Sun, X. Chen, J. Zhang, Z. Chen","doi":"10.1177/00220345251407594","DOIUrl":"https://doi.org/10.1177/00220345251407594","url":null,"abstract":"Tooth replantation is a clinical treatment commonly used for refractory periapical periodontitis, tooth avulsion, and autotransplantation. The condition of the periodontal ligament (PDL) is a prognostic factor that affects replantation outcomes. Various studies have been devoted to improving the repair of the PDL after replantation to improve the prognosis. Prostaglandin E2 (PGE2), an inflammatory mediator with critical effects involved in stem cell regulation as well as in tissue repair and regeneration, has been found to be increased after replantation. Thus, we hypothesized that the increased PGE2 in the PDL microenvironment may influence the viability of the PDL stem cells to affect PDL repair and improve replantation outcomes. We established a mouse model and found increased cyclooxygenase-2 expression and PGE2 concentrations within 1 to 3 d postreplantation. Human PDL stem cells (hPDLSCs) were stimulated with PGE2 and an EP4 agonist (L-902688) to assess viability, apoptosis, and cell cycle. Ribonucleic acid sequencing was performed to explore downstream mechanisms. The reanalysis of single-cell ribonucleic acid sequencing data suggested EP4 was the principal effective PGE2 receptor. PGE2 and EP4 agonist treatment enhanced the proliferation and viability of hPDLSCs. Ribonucleic acid sequencing identified transcriptional and immune response regulator (TCIM), a positive regulator of the Wnt/β-catenin signaling pathway, as a key downstream target. Knockdown of TCIM abrogated the proliferative effects of PGE2. In a mouse intervention model, the administration of SW033291 (a 15-hydroxyprostaglandin dehydrogenase inhibitor) or L-902688 significantly improved outcomes and increased TCIM expression in vivo. Our study demonstrates that PGE2 transiently increases in the PDL following replantation and enhances the proliferative capacity of hPDLSCs via EP4 activation, leading to the upregulation of TCIM and Wnt pathway activation. These findings offer mechanistic insight into periodontal repair and support the development of pharmaceutical strategies to improve replantation outcomes.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"39 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146160508","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 : 2026-02-12DOI: 10.1177/00220345251408835
C.C. Salomon-Ibarra, J. Wu, V. Toffolutti, E. Bernabe
This study evaluated the impact of the Soft Drinks Industry Levy (SDIL) on socioeconomic inequalities in hospital admissions for caries-related extractions in England. The study used monthly data on hospital admissions in NHS hospitals in England between March 2007 and December 2024 for 0- to 17-y-olds. Admission rates for caries-related extractions were standardised by population size (per 100,000 person-months) and stratified by area deprivation quintiles. The slope and relative indices of inequality (SII and RII) were used to evaluate the magnitude of the absolute and relative inequalities in admission rates by area deprivation. Admission rates for tonsillectomy were chosen as a negative control outcome. A segmented regression model was fitted with a parameterization that incorporated 4 key policy and contextual phases: SDIL announcement, implementation, COVID-19 lockdown, and postlockdown recovery. When the counterfactual and observed trends were compared, there were absolute reductions in the SII for caries-related extractions of 3.89 (95% CI: 2.38, 5.39) and 9.27 (95% CI: 7.15, 11.40) at 22 and 80 mo after implementation, corresponding to relative reductions of 9.16% (95% CI: 3.18, 15.13) and 25.54% (95% CI: 15.74, 35.34), respectively. There were also absolute reductions in the RII of 0.03 (95% CI: 0.01, 0.05) at 22 and 80 mo after implementation, corresponding to relative reductions of 13.52% (95% CI: 4.56, 22.48) and 12.74% (95% CI: 4.49, 20.99). No differences in SII or RII were observed for tonsillectomy admission rates. The introduction of the SDIL was associated with reductions in deprivation-related inequalities in admission rates for caries-related extractions among children in England.
{"title":"The UK Soft Drink Industry Levy and Inequalities in Caries-Related Extractions","authors":"C.C. Salomon-Ibarra, J. Wu, V. Toffolutti, E. Bernabe","doi":"10.1177/00220345251408835","DOIUrl":"https://doi.org/10.1177/00220345251408835","url":null,"abstract":"This study evaluated the impact of the Soft Drinks Industry Levy (SDIL) on socioeconomic inequalities in hospital admissions for caries-related extractions in England. The study used monthly data on hospital admissions in NHS hospitals in England between March 2007 and December 2024 for 0- to 17-y-olds. Admission rates for caries-related extractions were standardised by population size (per 100,000 person-months) and stratified by area deprivation quintiles. The slope and relative indices of inequality (SII and RII) were used to evaluate the magnitude of the absolute and relative inequalities in admission rates by area deprivation. Admission rates for tonsillectomy were chosen as a negative control outcome. A segmented regression model was fitted with a parameterization that incorporated 4 key policy and contextual phases: SDIL announcement, implementation, COVID-19 lockdown, and postlockdown recovery. When the counterfactual and observed trends were compared, there were absolute reductions in the SII for caries-related extractions of 3.89 (95% CI: 2.38, 5.39) and 9.27 (95% CI: 7.15, 11.40) at 22 and 80 mo after implementation, corresponding to relative reductions of 9.16% (95% CI: 3.18, 15.13) and 25.54% (95% CI: 15.74, 35.34), respectively. There were also absolute reductions in the RII of 0.03 (95% CI: 0.01, 0.05) at 22 and 80 mo after implementation, corresponding to relative reductions of 13.52% (95% CI: 4.56, 22.48) and 12.74% (95% CI: 4.49, 20.99). No differences in SII or RII were observed for tonsillectomy admission rates. The introduction of the SDIL was associated with reductions in deprivation-related inequalities in admission rates for caries-related extractions among children in England.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"37 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146160545","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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