Pub Date : 2025-10-16DOI: 10.1177/00220345251368263
K Seo,J Moon,R Bhat,U Mangal,S-H Choi,J-S Kwon
Dental caries caused by cariogenic biofilms is a significant challenge in modern dentistry, especially with aligner treatments, where biofilms can easily build up during prolonged use and lead to serious risks. Traditional antimicrobial methods focus on bacterial killing and often overlook the vital task of removing the biofilm matrix, allowing the quick reattachment of bacteria. In this study, we introduce an osmotic-driven biofilm removal strategy that harnesses osmotic dynamics to remove entire biofilm structures physically. Internal osmotic pressure is generated by a precisely designed cationic copolymer, triggering controlled detachment of the biofilm matrix. When tested in vitro on Streptococcus mutans biofilms grown on dental aligners and in hard-to-reach interproximal spaces, our method eliminated biofilms more efficiently than traditional cleaning methods. The technique showed concentration-dependent cytotoxicity, highlighting the need for further polymer optimization. Overall, our osmotic-driven biofilm removal strategy significantly advances biofilm control strategies, offering a novel solution for improving oral health and presenting a potential physical removal method for medical settings.
{"title":"Cationic Polymer for Aligner and Oral Biofilm Removal via Osmotic Mechanism.","authors":"K Seo,J Moon,R Bhat,U Mangal,S-H Choi,J-S Kwon","doi":"10.1177/00220345251368263","DOIUrl":"https://doi.org/10.1177/00220345251368263","url":null,"abstract":"Dental caries caused by cariogenic biofilms is a significant challenge in modern dentistry, especially with aligner treatments, where biofilms can easily build up during prolonged use and lead to serious risks. Traditional antimicrobial methods focus on bacterial killing and often overlook the vital task of removing the biofilm matrix, allowing the quick reattachment of bacteria. In this study, we introduce an osmotic-driven biofilm removal strategy that harnesses osmotic dynamics to remove entire biofilm structures physically. Internal osmotic pressure is generated by a precisely designed cationic copolymer, triggering controlled detachment of the biofilm matrix. When tested in vitro on Streptococcus mutans biofilms grown on dental aligners and in hard-to-reach interproximal spaces, our method eliminated biofilms more efficiently than traditional cleaning methods. The technique showed concentration-dependent cytotoxicity, highlighting the need for further polymer optimization. Overall, our osmotic-driven biofilm removal strategy significantly advances biofilm control strategies, offering a novel solution for improving oral health and presenting a potential physical removal method for medical settings.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"10 1","pages":"220345251368263"},"PeriodicalIF":7.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305736","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 : 2025-10-16DOI: 10.1177/00220345251363561
T Tuwatnawanit,N Anthwal,A S Tucker
The temporomandibular joint (TMJ) plays a critical role in the daily activities of mastication and communication, with disorders of the TMJ significantly impairing quality of life. Temporomandibular disorders (TMDs) are highly prevalent, presenting a pressing need for regenerative therapies. The TMJ's key components-condyle, TMJ disc, and glenoid fossa-are crucial for proper function; however, the limited self-repair capability of these tissues makes managing TMJ pathology particularly challenging. Emerging research in animal models has emphasized the importance of fibrocartilage stem/progenitor cells (FCSCs) located in and around the superficial layers of the condyle. Lineage tracing of condylar FCSCs in vivo has identified subpopulations with different contributions to growth and homeostasis, providing potential targets for regenerative therapies. In addition to the FCSCs, niche-supporting cells have been recently identified in the superficial layers of the condyle, further highlighting the complex cellular environment of the TMJ. Several signaling pathways, including Wnt, Hedgehog, and Notch, play pivotal roles in establishing cell fate in the developing and growing TMJ and have been additionally implicated in both the control of FCSC populations and progression of TMDs. Recent research has used this understanding of the signaling pathways involved in the creation of the joint to stimulate the endogenous stem cells/FCSCs of the adult in vivo, leading to enhancement of regenerative capacity in mouse, rat, rabbit, and porcine injury and disease models. Manipulation of signaling pathways has been combined with advanced bioengineering techniques, providing scaffolds to allow controlled dispersal of activators and inhibitors. Such advances in understanding the triggers and molecular mechanisms that control TMJ FCSCs, combined with improved targeting of specific signaling pathways, have opened new avenues for regenerative therapies. These insights have begun to be leveraged in the development of novel hydrogel-based injectable regenerative therapeutic approaches to not only alleviate symptoms but also promote true regeneration of TMJ structures.
{"title":"Activating Endogenous Condylar Stem Cells to Enhance TMJ Repair.","authors":"T Tuwatnawanit,N Anthwal,A S Tucker","doi":"10.1177/00220345251363561","DOIUrl":"https://doi.org/10.1177/00220345251363561","url":null,"abstract":"The temporomandibular joint (TMJ) plays a critical role in the daily activities of mastication and communication, with disorders of the TMJ significantly impairing quality of life. Temporomandibular disorders (TMDs) are highly prevalent, presenting a pressing need for regenerative therapies. The TMJ's key components-condyle, TMJ disc, and glenoid fossa-are crucial for proper function; however, the limited self-repair capability of these tissues makes managing TMJ pathology particularly challenging. Emerging research in animal models has emphasized the importance of fibrocartilage stem/progenitor cells (FCSCs) located in and around the superficial layers of the condyle. Lineage tracing of condylar FCSCs in vivo has identified subpopulations with different contributions to growth and homeostasis, providing potential targets for regenerative therapies. In addition to the FCSCs, niche-supporting cells have been recently identified in the superficial layers of the condyle, further highlighting the complex cellular environment of the TMJ. Several signaling pathways, including Wnt, Hedgehog, and Notch, play pivotal roles in establishing cell fate in the developing and growing TMJ and have been additionally implicated in both the control of FCSC populations and progression of TMDs. Recent research has used this understanding of the signaling pathways involved in the creation of the joint to stimulate the endogenous stem cells/FCSCs of the adult in vivo, leading to enhancement of regenerative capacity in mouse, rat, rabbit, and porcine injury and disease models. Manipulation of signaling pathways has been combined with advanced bioengineering techniques, providing scaffolds to allow controlled dispersal of activators and inhibitors. Such advances in understanding the triggers and molecular mechanisms that control TMJ FCSCs, combined with improved targeting of specific signaling pathways, have opened new avenues for regenerative therapies. These insights have begun to be leveraged in the development of novel hydrogel-based injectable regenerative therapeutic approaches to not only alleviate symptoms but also promote true regeneration of TMJ structures.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"78 1","pages":"220345251363561"},"PeriodicalIF":7.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305680","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 : 2025-10-16DOI: 10.1177/00220345251368752
Z Ye,X Zhou,J Yu,X Chen,Y Huang,Q Xia,Y Xie,X Tong,Z Chen,Y Li,L Zhu,C Wen,J Lin,J Ma
Endocrowns represent a minimally invasive treatment option for endodontically treated teeth. However, in the anterior dentition, they are more likely to cause fractures in the abutment teeth due to the influence of lateral forces. Developing endocrowns that closely replicate the mechanical properties of the different components of natural teeth offers a promising strategy for improving the biomechanical performance of single-component restorations. Therefore, this study reports a novel multilevel ceramic composite achieved through fabrication of a diamond-topology lithium disilicate (LD) ceramic scaffold using vat photopolymerization, followed by toughening through potassium nitrate ion exchange (IE) and epoxy resin infiltration. This ceramic composite exhibited mechanical properties close to those of human dentin and therefore can prevent catastrophic stress-induced fractures of the abutment teeth due to enhanced toughness. Heating treatment and phase analyses were conducted to determine the optimal debinding and sintering parameters. Residual stress measurements, flexural strength testing, and microhardness evaluations were performed to assess the mechanical properties of the IE-toughened LD. In addition, the elastic modulus, compressive strength, and toughness of the ceramic composite were comprehensively characterized, using Vita Enamic and human dentin as reference materials. With the optimization of the heat-treatment and IE processes, the ceramic composite achieved a maximum compressive strength of 217 ± 11.8 MPa and a minimum elastic modulus of 3.7 ± 0.1 GPa, similar to the elastic modulus of human dentin (1.9 ± 0.4 GPa). In addition, the 0.25RD (relative density) composite group showed a maximum energy absorption of 37.7 ± 1.9 MJ/m³. The quasi in situ compression test revealed that the enhanced toughness primarily resulted from microcrack aggregation, interface delamination, and macroscopic crack splitting.
{"title":"A Biomimetic Li2Si2O5 Composite with High Energy Absorption for Endocrowns.","authors":"Z Ye,X Zhou,J Yu,X Chen,Y Huang,Q Xia,Y Xie,X Tong,Z Chen,Y Li,L Zhu,C Wen,J Lin,J Ma","doi":"10.1177/00220345251368752","DOIUrl":"https://doi.org/10.1177/00220345251368752","url":null,"abstract":"Endocrowns represent a minimally invasive treatment option for endodontically treated teeth. However, in the anterior dentition, they are more likely to cause fractures in the abutment teeth due to the influence of lateral forces. Developing endocrowns that closely replicate the mechanical properties of the different components of natural teeth offers a promising strategy for improving the biomechanical performance of single-component restorations. Therefore, this study reports a novel multilevel ceramic composite achieved through fabrication of a diamond-topology lithium disilicate (LD) ceramic scaffold using vat photopolymerization, followed by toughening through potassium nitrate ion exchange (IE) and epoxy resin infiltration. This ceramic composite exhibited mechanical properties close to those of human dentin and therefore can prevent catastrophic stress-induced fractures of the abutment teeth due to enhanced toughness. Heating treatment and phase analyses were conducted to determine the optimal debinding and sintering parameters. Residual stress measurements, flexural strength testing, and microhardness evaluations were performed to assess the mechanical properties of the IE-toughened LD. In addition, the elastic modulus, compressive strength, and toughness of the ceramic composite were comprehensively characterized, using Vita Enamic and human dentin as reference materials. With the optimization of the heat-treatment and IE processes, the ceramic composite achieved a maximum compressive strength of 217 ± 11.8 MPa and a minimum elastic modulus of 3.7 ± 0.1 GPa, similar to the elastic modulus of human dentin (1.9 ± 0.4 GPa). In addition, the 0.25RD (relative density) composite group showed a maximum energy absorption of 37.7 ± 1.9 MJ/m³. The quasi in situ compression test revealed that the enhanced toughness primarily resulted from microcrack aggregation, interface delamination, and macroscopic crack splitting.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"9 1","pages":"220345251368752"},"PeriodicalIF":7.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305733","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 : 2025-10-16DOI: 10.1177/00220345251368273
Y J Zhang,Y Li,S Y Mo,J W Liu,X T Song,K Y Fu,Q F Xie,X X Xu,Y Cao
Acute occlusal interference may induce chronic masticatory myalgia in some individuals. The potential factors and underlying mechanisms that predispose one to occlusion-related masticatory myalgia remain unclear. Anxiety has been shown to facilitate pain perception. The ventral tegmental area, a critical component of the mesolimbic dopamine circuit, is involved in the neural networks shared by anxiety and pain. Whether anxiety levels influence masticatory myalgia induced by occlusal interference and what role the ventral tegmental area plays in this interaction have yet to be fully elucidated. In this study, we quantified the inborn variability in anxiety levels of male Sprague-Dawley rats using the elevated plus maze. We observed that high anxiety levels enhanced mechanical hypersensitivity in masseter muscle following application of experimental occlusion interference. Immunofluorescence and in vivo electrophysiologic experiments revealed differences in the activity of dopaminergic neurons and low-frequency oscillations in the ventral tegmental area of rats with varying anxiety levels following occlusion interference. Chemogenetic manipulations of dopaminergic neurons in the ventral tegmental area influenced the facilitatory effect of anxiety on occlusion interference-induced masseteric hyperalgesia. These findings provide the first evidence that anxiety can facilitate occlusion interference-induced masticatory myalgia, with the ventral tegmental area playing a crucial role in this neurobiological process.
{"title":"Anxiety Promotes Occlusal Interference-Induced Myalgia via the Mesolimbic System.","authors":"Y J Zhang,Y Li,S Y Mo,J W Liu,X T Song,K Y Fu,Q F Xie,X X Xu,Y Cao","doi":"10.1177/00220345251368273","DOIUrl":"https://doi.org/10.1177/00220345251368273","url":null,"abstract":"Acute occlusal interference may induce chronic masticatory myalgia in some individuals. The potential factors and underlying mechanisms that predispose one to occlusion-related masticatory myalgia remain unclear. Anxiety has been shown to facilitate pain perception. The ventral tegmental area, a critical component of the mesolimbic dopamine circuit, is involved in the neural networks shared by anxiety and pain. Whether anxiety levels influence masticatory myalgia induced by occlusal interference and what role the ventral tegmental area plays in this interaction have yet to be fully elucidated. In this study, we quantified the inborn variability in anxiety levels of male Sprague-Dawley rats using the elevated plus maze. We observed that high anxiety levels enhanced mechanical hypersensitivity in masseter muscle following application of experimental occlusion interference. Immunofluorescence and in vivo electrophysiologic experiments revealed differences in the activity of dopaminergic neurons and low-frequency oscillations in the ventral tegmental area of rats with varying anxiety levels following occlusion interference. Chemogenetic manipulations of dopaminergic neurons in the ventral tegmental area influenced the facilitatory effect of anxiety on occlusion interference-induced masseteric hyperalgesia. These findings provide the first evidence that anxiety can facilitate occlusion interference-induced masticatory myalgia, with the ventral tegmental area playing a crucial role in this neurobiological process.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"46 1","pages":"220345251368273"},"PeriodicalIF":7.6,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305737","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 : 2025-10-15DOI: 10.1177/00220345251356408
F Schwendicke,S K Sidhu,J L Ferracane,A Tichy,N S Jakubovics
Generative artificial intelligence (AI) has the capability to generate new content-including text, code, imagery, video, and speech-based on human prompts and is entering dental and oral research. By retrieving, analyzing, summarizing, and contextualizing vast datasets, generative AI offers substantial potential to enhance scientific workflows. It can improve documentation, communication, and reproducibility while saving time and accelerating discovery. However, its integration into research brings significant ethical, societal, and scientific challenges. Concerns include embedded data biases, automation bias, overreliance, and error propagation, all requiring critical human oversight. Furthermore, generative AI raises complex issues around plagiarism, fraud, attribution, and reproducibility, compounded by the potential for AI "hallucinations" or fabricated content. Addressing these concerns demands transparency, robust verification processes, ethical compliance, and clear documentation distinguishing synthetic from real-world data. Several scientific and regulatory bodies have published guidelines to support responsible AI use. Recommendations relevant to scientists in dental, oral, and craniofacial research include transparent disclosure of AI tools and methods, thorough verification of AI outputs, ethical oversight, and active monitoring. Scientists are urged to work collaboratively with stakeholders to enforce these principles and engage the public in the evolving discourse. The risk of misuse, particularly through fraudulent AI-generated publications, is growing. Paper mills exploiting generative AI can produce fabricated or manipulated articles, which may mislead the scientific community and distort evidence bases. Coordinated action, involving journals, institutions, and ethics bodies, is essential to combat these threats. As generative AI continues to evolve, adaptive and harmonized guidelines will be necessary to safeguard scientific integrity. Researchers, reviewers, and editors must play a proactive role in ensuring that AI serves to advance-not undermine-the quality and trustworthiness of dental and oral science.
{"title":"Generative AI: Opportunities, Risks, and Responsibilities for Oral Sciences.","authors":"F Schwendicke,S K Sidhu,J L Ferracane,A Tichy,N S Jakubovics","doi":"10.1177/00220345251356408","DOIUrl":"https://doi.org/10.1177/00220345251356408","url":null,"abstract":"Generative artificial intelligence (AI) has the capability to generate new content-including text, code, imagery, video, and speech-based on human prompts and is entering dental and oral research. By retrieving, analyzing, summarizing, and contextualizing vast datasets, generative AI offers substantial potential to enhance scientific workflows. It can improve documentation, communication, and reproducibility while saving time and accelerating discovery. However, its integration into research brings significant ethical, societal, and scientific challenges. Concerns include embedded data biases, automation bias, overreliance, and error propagation, all requiring critical human oversight. Furthermore, generative AI raises complex issues around plagiarism, fraud, attribution, and reproducibility, compounded by the potential for AI \"hallucinations\" or fabricated content. Addressing these concerns demands transparency, robust verification processes, ethical compliance, and clear documentation distinguishing synthetic from real-world data. Several scientific and regulatory bodies have published guidelines to support responsible AI use. Recommendations relevant to scientists in dental, oral, and craniofacial research include transparent disclosure of AI tools and methods, thorough verification of AI outputs, ethical oversight, and active monitoring. Scientists are urged to work collaboratively with stakeholders to enforce these principles and engage the public in the evolving discourse. The risk of misuse, particularly through fraudulent AI-generated publications, is growing. Paper mills exploiting generative AI can produce fabricated or manipulated articles, which may mislead the scientific community and distort evidence bases. Coordinated action, involving journals, institutions, and ethics bodies, is essential to combat these threats. As generative AI continues to evolve, adaptive and harmonized guidelines will be necessary to safeguard scientific integrity. Researchers, reviewers, and editors must play a proactive role in ensuring that AI serves to advance-not undermine-the quality and trustworthiness of dental and oral science.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"213 1","pages":"220345251356408"},"PeriodicalIF":7.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288607","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 : 2025-10-03DOI: 10.1177/00220345251384972
{"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}
Pub Date : 2025-10-03DOI: 10.1177/00220345251350135
L Huang,X Yang,Z Bai,Y Lu,J Bian,H Xie,C Chen,K Chen
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.
{"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}
Pub Date : 2025-09-22DOI: 10.1177/00220345251362203
X Li,Z Cao,X Chen,Y Xu,H Liu,X Wang,J Wang,L Hu,S Wang
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.
{"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}
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.
{"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}
Pub Date : 2025-09-20DOI: 10.1177/00220345251360752
K Martin,R Dabaja,M J Mianecki,A Sheikh,V Maglaras,M H A Saleh,J T Decker,A M Decker
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.
{"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}
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