Pub Date : 2025-12-18DOI: 10.1177/00220345251387713
L Kumaralingam,M H Hoang,K C T Nguyen,N R Kaipatur,H B V Dinh,J Alavi,K Punithakumar,E H M Lou,P W Major,L H Le
Intraoral ultrasound (IUS) is emerging as a valuable imaging modality in dentistry, offering noninvasive, radiation-free, real-time visualization of periodontal structures. Unlike traditional imaging methods, IUS enables dynamic assessments during clinical procedures, supporting diagnostic and treatment-planning capabilities. The accurate evaluation of parameters such as alveolar bone level (ABL), gingival thickness (GT), and alveolar bone thickness (ABT) is critical for diagnosing periodontal diseases. However, current assessment techniques are typically manual, time-consuming, and based on static images, leading to inter-operator variability and limiting real-time application. To address these gaps, this study aimed to develop OralSAM, an end-to-end machine learning network for automated segmentation and quantitative assessment of periodontal structures in IUS videos. The network segments gingiva, enamel, alveolar bone, and cementum, followed by a morphological analysis pipeline to extract clinically relevant measurements. A total of 158 IUS videos from 30 orthodontic patients were included, and the dataset was split into training, validation, and testing subsets following a 6:2:2 ratio. The segmentation performance of OralSAM, evaluated against expert-annotated ground truth, demonstrated high segmentation accuracy across key periodontal structures. Morphological measurements derived from the machine learning network also exhibited strong inter-rater reliability, as confirmed by Bland-Altman analysis, which demonstrated narrow limits of agreement (LOAs) for ABL (mean bias = -0.063 mm, LOA = -0.771 to 0.646 mm), GT (mean bias = -0.063 mm, LOA = -0.24 to 0.115 mm), and ABT (mean bias = -0.002 mm, LOA = -0.104 to 0.1 mm). The intraclass correlation coefficients were 0.893 (95% confidence interval [CI], 0.864 to 0.915) for ABL, 0.918 (95% CI, 0.768 to 0.960) for GT, and 0.848 (95% CI, 0.806 to 0.880) for ABT. These findings highlight OralSAM's capability to accurately delineate periodontal structures and provide consistent assessments. The proposed framework shows strong potential for integration into routine chairside workflows, enabling early detection, real-time monitoring, and personalized management of periodontal disease.
口腔内超声（IUS）正在成为一种有价值的牙科成像方式，提供无创，无辐射，牙周结构的实时可视化。与传统的成像方法不同，IUS能够在临床过程中进行动态评估，支持诊断和治疗计划能力。准确评估牙槽骨水平（ABL）、牙龈厚度（GT）和牙槽骨厚度（ABT）等参数对牙周病的诊断至关重要。然而，目前的评估技术通常是手动的，耗时的，并且基于静态图像，导致操作员之间的变化，限制了实时应用。为了解决这些差距，本研究旨在开发OralSAM，这是一个端到端机器学习网络，用于自动分割和定量评估IUS视频中的牙周结构。网络分割牙龈、牙釉质、牙槽骨和牙骨质，然后通过形态学分析管道提取临床相关测量值。共纳入了来自30名正畸患者的158个IUS视频，并按照6:2:2的比例将数据集分为训练、验证和测试子集。OralSAM的分割性能，根据专家注释的基础事实进行评估，在关键牙周结构上显示出很高的分割准确性。Bland-Altman分析证实，机器学习网络的形态学测量结果也表现出很强的评分间可靠性，结果表明，ABL（平均偏差= -0.063 mm, LOA = -0.771至0.646 mm）、GT（平均偏差= -0.063 mm, LOA = -0.24至0.115 mm）和ABT（平均偏差= -0.002 mm, LOA = -0.104至0.1 mm）的一致性限制（LOAs）较窄。ABL的类内相关系数为0.893(95%可信区间[CI]， 0.864至0.915)，GT的类内相关系数为0.918 (95% CI， 0.768至0.960)，ABT的类内相关系数为0.848 （95% CI， 0.806至0.880）。这些发现突出了OralSAM准确描绘牙周结构并提供一致评估的能力。拟议的框架显示出整合到常规主席工作流程中的强大潜力，从而实现牙周病的早期发现、实时监测和个性化管理。
{"title":"Automatic Assessment of Periodontium Complex in Intraoral Ultrasound Videos.","authors":"L Kumaralingam,M H Hoang,K C T Nguyen,N R Kaipatur,H B V Dinh,J Alavi,K Punithakumar,E H M Lou,P W Major,L H Le","doi":"10.1177/00220345251387713","DOIUrl":"https://doi.org/10.1177/00220345251387713","url":null,"abstract":"Intraoral ultrasound (IUS) is emerging as a valuable imaging modality in dentistry, offering noninvasive, radiation-free, real-time visualization of periodontal structures. Unlike traditional imaging methods, IUS enables dynamic assessments during clinical procedures, supporting diagnostic and treatment-planning capabilities. The accurate evaluation of parameters such as alveolar bone level (ABL), gingival thickness (GT), and alveolar bone thickness (ABT) is critical for diagnosing periodontal diseases. However, current assessment techniques are typically manual, time-consuming, and based on static images, leading to inter-operator variability and limiting real-time application. To address these gaps, this study aimed to develop OralSAM, an end-to-end machine learning network for automated segmentation and quantitative assessment of periodontal structures in IUS videos. The network segments gingiva, enamel, alveolar bone, and cementum, followed by a morphological analysis pipeline to extract clinically relevant measurements. A total of 158 IUS videos from 30 orthodontic patients were included, and the dataset was split into training, validation, and testing subsets following a 6:2:2 ratio. The segmentation performance of OralSAM, evaluated against expert-annotated ground truth, demonstrated high segmentation accuracy across key periodontal structures. Morphological measurements derived from the machine learning network also exhibited strong inter-rater reliability, as confirmed by Bland-Altman analysis, which demonstrated narrow limits of agreement (LOAs) for ABL (mean bias = -0.063 mm, LOA = -0.771 to 0.646 mm), GT (mean bias = -0.063 mm, LOA = -0.24 to 0.115 mm), and ABT (mean bias = -0.002 mm, LOA = -0.104 to 0.1 mm). The intraclass correlation coefficients were 0.893 (95% confidence interval [CI], 0.864 to 0.915) for ABL, 0.918 (95% CI, 0.768 to 0.960) for GT, and 0.848 (95% CI, 0.806 to 0.880) for ABT. These findings highlight OralSAM's capability to accurately delineate periodontal structures and provide consistent assessments. The proposed framework shows strong potential for integration into routine chairside workflows, enabling early detection, real-time monitoring, and personalized management of periodontal disease.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"24 1","pages":"220345251387713"},"PeriodicalIF":7.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777276","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: 10.1177/00220345251392876
L M Dias,A C Pavarina,W L Siqueira
Oral candidiasis is primarily caused by Candida albicans; however, bacteria such as Streptococcus mutans can also coexist and cooperate within the same biofilm. This study evaluated the combined effects of Histatin 3 (His3) and Histatin 5 (His5) with antimicrobial photodynamic therapy (aPDT) using a 3-dimensional oral epithelium model infected with mixed biofilms of C. albicans (polyene-resistant strains) and S. mutans. The tissues, divided into groups (His3 + aPDT, His5+aPDT, His3, His5, or aPDT), were first treated with the salivary proteins His3 or His5 (2 h, 37 °C, 60 rpm/min) followed by infection with mixed biofilms. After 24 h of biofilm formation, aPDT was applied (PDZ: 200 mg/L; LED light: 660 nm with 50 J/cm²) using intermittent irradiation cycles (n = 9/group). Biofilm viability (CFU/mL), total proteins (intracellular and extracellular), and proteomic analysis were performed. Biocompatibility and tissue invasion were also assessed by MTT assays and histological analysis, respectively. His3+aPDT and His5+aPDT reduced mixed biofilm viability by 67% (P = 0.0038) and 65% (P = 0.0062), respectively. His3 and His5 alone promoted a 35% to 45% (P = 0.018; P = 00.24) reduction, while aPDT alone reduced by 50% to 55% (P = 0.022; P = 0.037). Combined treatments enhanced efficacy by ~30% compared with individual treatments. Histological evaluation also confirmed reduced biofilm penetration and hyphal formation, particularly with His5+aPDT. Proteomic analysis of the proteins from C. albicans revealed the downregulation of structural and transport proteins, which can likely weaken the biofilm. The combination of His3 and His5 with aPDT enhances antimicrobial efficacy against resistant multispecies biofilms while maintaining biocompatibility. By reducing biofilm viability and compromising proteins, this approach provides a promising alternative for treating oral candidiasis associated with polyene-resistant C. albicans species.
{"title":"Histatin-Photodynamic Therapy for Polyene-Resistant Biofilms in a 3D Model.","authors":"L M Dias,A C Pavarina,W L Siqueira","doi":"10.1177/00220345251392876","DOIUrl":"https://doi.org/10.1177/00220345251392876","url":null,"abstract":"Oral candidiasis is primarily caused by Candida albicans; however, bacteria such as Streptococcus mutans can also coexist and cooperate within the same biofilm. This study evaluated the combined effects of Histatin 3 (His3) and Histatin 5 (His5) with antimicrobial photodynamic therapy (aPDT) using a 3-dimensional oral epithelium model infected with mixed biofilms of C. albicans (polyene-resistant strains) and S. mutans. The tissues, divided into groups (His3 + aPDT, His5+aPDT, His3, His5, or aPDT), were first treated with the salivary proteins His3 or His5 (2 h, 37 °C, 60 rpm/min) followed by infection with mixed biofilms. After 24 h of biofilm formation, aPDT was applied (PDZ: 200 mg/L; LED light: 660 nm with 50 J/cm²) using intermittent irradiation cycles (n = 9/group). Biofilm viability (CFU/mL), total proteins (intracellular and extracellular), and proteomic analysis were performed. Biocompatibility and tissue invasion were also assessed by MTT assays and histological analysis, respectively. His3+aPDT and His5+aPDT reduced mixed biofilm viability by 67% (P = 0.0038) and 65% (P = 0.0062), respectively. His3 and His5 alone promoted a 35% to 45% (P = 0.018; P = 00.24) reduction, while aPDT alone reduced by 50% to 55% (P = 0.022; P = 0.037). Combined treatments enhanced efficacy by ~30% compared with individual treatments. Histological evaluation also confirmed reduced biofilm penetration and hyphal formation, particularly with His5+aPDT. Proteomic analysis of the proteins from C. albicans revealed the downregulation of structural and transport proteins, which can likely weaken the biofilm. The combination of His3 and His5 with aPDT enhances antimicrobial efficacy against resistant multispecies biofilms while maintaining biocompatibility. By reducing biofilm viability and compromising proteins, this approach provides a promising alternative for treating oral candidiasis associated with polyene-resistant C. albicans species.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"248 1","pages":"220345251392876"},"PeriodicalIF":7.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777275","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: 10.1177/00220345251397375
E. Juuri, S. Strausz, Md. R. Hasan, M. Hongqiang, T. Jónsson, Á. Thordarsson, G. Auðólfsson, D. Gudbjartsson, H. Stefansson, P. Nieminen, H.M. Ollila, D.P. Rice
Mandibular retrognathia is a common craniofacial anomaly characterized by a posteriorly positioned mandible, which can affect a person’s oral function, esthetics, and quality of life. While facial characteristics are widely acknowledged to have a hereditary component, the etiology of this skeletal anomaly is poorly understood. This study aims to identify genetic loci associated with mandibular retrognathia and help elucidate its causes. Using the FinnGen cohort (2,647 cases, 497,020 controls), a genome-wide association study identified 2 regions of genome-wide significance with lead single-nucleotide polymorphisms rs227727 at NOG locus and rs7225448 at SOX9 locus. Interestingly, both associations were driven by results from females. The rs227727 association was replicated in an independent cohort from Iceland. Functional annotation revealed that rs227727 disrupts an enhancer regulating NOG , a gene important for normal bone and cartilage development and previously implicated in craniofacial anomalies. Morphological analyses of Nog-/- mice revealed mandibular retrognathia-like features, including reduced mandibular length and condylar width. Variants in linkage disequilibrium with rs7225448 were located within distal enhancers near SOX9 , a transcription factor essential for cartilage development. SOX9 mutations are known to cause Robin sequence with its constituent severe mandibular retrognathia. In addition, regional analysis revealed variation in the prevalence of mandibular retrognathia across Finland’s 18 administrative regions, which was correlated especially with the rs227727 risk allele regional prevalence. These findings highlight genetic contributors to mandibular retrognathia and emphasize the importance of long-range regulatory elements in craniofacial development. By integrating genetic, functional, and epidemiological data, this study enhances our understanding of the genetic architecture underlying craniofacial anomalies.
{"title":"Variants Near NOG and SOX9 Are Associated with Mandibular Retrognathia","authors":"E. Juuri, S. Strausz, Md. R. Hasan, M. Hongqiang, T. Jónsson, Á. Thordarsson, G. Auðólfsson, D. Gudbjartsson, H. Stefansson, P. Nieminen, H.M. Ollila, D.P. Rice","doi":"10.1177/00220345251397375","DOIUrl":"https://doi.org/10.1177/00220345251397375","url":null,"abstract":"Mandibular retrognathia is a common craniofacial anomaly characterized by a posteriorly positioned mandible, which can affect a person’s oral function, esthetics, and quality of life. While facial characteristics are widely acknowledged to have a hereditary component, the etiology of this skeletal anomaly is poorly understood. This study aims to identify genetic loci associated with mandibular retrognathia and help elucidate its causes. Using the FinnGen cohort (2,647 cases, 497,020 controls), a genome-wide association study identified 2 regions of genome-wide significance with lead single-nucleotide polymorphisms rs227727 at <jats:italic toggle=\"yes\">NOG</jats:italic> locus and rs7225448 at <jats:italic toggle=\"yes\">SOX9</jats:italic> locus. Interestingly, both associations were driven by results from females. The rs227727 association was replicated in an independent cohort from Iceland. Functional annotation revealed that rs227727 disrupts an enhancer regulating <jats:italic toggle=\"yes\">NOG</jats:italic> , a gene important for normal bone and cartilage development and previously implicated in craniofacial anomalies. Morphological analyses of <jats:italic toggle=\"yes\">Nog</jats:italic> <jats:sup>-/-</jats:sup> mice revealed mandibular retrognathia-like features, including reduced mandibular length and condylar width. Variants in linkage disequilibrium with rs7225448 were located within distal enhancers near <jats:italic toggle=\"yes\">SOX9</jats:italic> , a transcription factor essential for cartilage development. <jats:italic toggle=\"yes\">SOX9</jats:italic> mutations are known to cause Robin sequence with its constituent severe mandibular retrognathia. In addition, regional analysis revealed variation in the prevalence of mandibular retrognathia across Finland’s 18 administrative regions, which was correlated especially with the rs227727 risk allele regional prevalence. These findings highlight genetic contributors to mandibular retrognathia and emphasize the importance of long-range regulatory elements in craniofacial development. By integrating genetic, functional, and epidemiological data, this study enhances our understanding of the genetic architecture underlying craniofacial anomalies.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"93 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770727","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: 10.1177/00220345251400253
M. Zhang, L. Meng, X. Li, Y. Zhang, R. Yuan, S. Liu, H. Liu, M. Li
Diabetic periodontitis (DPD) is recognized as a common complication of diabetes mellitus. It progresses rapidly and causes severe destruction of periodontal tissues. The condition often leads to a poor prognosis for affected patients. CD4 + T lymphocytes—pivotal effector cells in adaptive immunity—play a central role in driving DPD pathogenesis through immunometabolic dysregulation. The functional dynamics and contributions of CD4 + T cells to DPD pathogenesis remain insufficiently investigated. To investigate this, single-cell RNA sequencing data from the gingival tissues of DPD mice in the Gene Expression Omnibus database were analyzed, identifying significant CD4 + T cell senescence in DPD. This finding was experimentally confirmed using a DPD mouse model. Furthermore, through adoptive transfer experiments, we demonstrated that in DPD, senescent CD4 + T cells exacerbate the release of senescence-associated secretory phenotype (SASP). SASP chemokines recruit immune cells, which in turn release additional inflammatory factors, creating a self-amplifying cycle that disrupts the Th17/Treg balance and worsens bone loss. This reveals the pathogenic role of senescent CD4 + T cells, whereas adoptive transfer of normal CD4 + T cells rescues this pathological process. Bioinformatics analysis linked CD4 + T cell senescence to the JAK-STAT and p38 MAPK signaling pathways. Subsequent experimental validation detected upregulated JAK-STAT and p38 MAPK activity in DPD gingival tissues. Pharmacological inhibition of these pathways in vitro markedly reduced CD4 + T cell senescence. Mechanistically, JAK-STAT activation elevated mitochondrial reactive oxygen species (mtROS), subsequently triggering the tumor necrosis factor α (TNF-α)–p38 MAPK axis. This cascade led to p53 upregulation and enhanced cellular senescence. This study clarifies the immunopathological mechanisms underlying CD4 + T cell senescence in DPD, emphasizing the crosstalk between metabolic dysregulation via JAK-STAT-mtROS and inflammatory signaling through TNF-α–p38 MAPK (proinflammatory signaling cascade). These findings provide novel perspectives for developing therapeutic strategies targeting CD4 + T cell senescence in DPD, thereby mitigating inflammatory factor release and inhibiting alveolar bone resorption.
{"title":"Senescent CD4 + T Cells Drive Diabetic Periodontitis via JAK-STAT-ROS-p38 MAPK","authors":"M. Zhang, L. Meng, X. Li, Y. Zhang, R. Yuan, S. Liu, H. Liu, M. Li","doi":"10.1177/00220345251400253","DOIUrl":"https://doi.org/10.1177/00220345251400253","url":null,"abstract":"Diabetic periodontitis (DPD) is recognized as a common complication of diabetes mellitus. It progresses rapidly and causes severe destruction of periodontal tissues. The condition often leads to a poor prognosis for affected patients. CD4 <jats:sup>+</jats:sup> T lymphocytes—pivotal effector cells in adaptive immunity—play a central role in driving DPD pathogenesis through immunometabolic dysregulation. The functional dynamics and contributions of CD4 <jats:sup>+</jats:sup> T cells to DPD pathogenesis remain insufficiently investigated. To investigate this, single-cell RNA sequencing data from the gingival tissues of DPD mice in the Gene Expression Omnibus database were analyzed, identifying significant CD4 <jats:sup>+</jats:sup> T cell senescence in DPD. This finding was experimentally confirmed using a DPD mouse model. Furthermore, through adoptive transfer experiments, we demonstrated that in DPD, senescent CD4 <jats:sup>+</jats:sup> T cells exacerbate the release of senescence-associated secretory phenotype (SASP). SASP chemokines recruit immune cells, which in turn release additional inflammatory factors, creating a self-amplifying cycle that disrupts the Th17/Treg balance and worsens bone loss. This reveals the pathogenic role of senescent CD4 <jats:sup>+</jats:sup> T cells, whereas adoptive transfer of normal CD4 <jats:sup>+</jats:sup> T cells rescues this pathological process. Bioinformatics analysis linked CD4 <jats:sup>+</jats:sup> T cell senescence to the JAK-STAT and p38 MAPK signaling pathways. Subsequent experimental validation detected upregulated JAK-STAT and p38 MAPK activity in DPD gingival tissues. Pharmacological inhibition of these pathways in vitro markedly reduced CD4 <jats:sup>+</jats:sup> T cell senescence. Mechanistically, JAK-STAT activation elevated mitochondrial reactive oxygen species (mtROS), subsequently triggering the tumor necrosis factor α (TNF-α)–p38 MAPK axis. This cascade led to p53 upregulation and enhanced cellular senescence. This study clarifies the immunopathological mechanisms underlying CD4 <jats:sup>+</jats:sup> T cell senescence in DPD, emphasizing the crosstalk between metabolic dysregulation via JAK-STAT-mtROS and inflammatory signaling through TNF-α–p38 MAPK (proinflammatory signaling cascade). These findings provide novel perspectives for developing therapeutic strategies targeting CD4 <jats:sup>+</jats:sup> T cell senescence in DPD, thereby mitigating inflammatory factor release and inhibiting alveolar bone resorption.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"1 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770729","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: 10.1177/00220345251401502
S. Cha, W. Gao, J. Wang, Z. Tan, C. Zhou, Q. Zhao, D. Bai
Osteoarthritis (OA) is the most prevalent degenerative disorder of the temporomandibular joint (TMJ), with aging as a major risk factor. Although circadian clocks are essential for maintaining tissue homeostasis and metabolic balance, the influence of aging on tissue-specific circadian regulation of TMJ homeostasis remains unclear. Here, using aged mice and transgenic mouse models, we demonstrated that the mesenchymal circadian clock is indispensable for preserving TMJ osteochondral integrity during aging. Loss of the core circadian regulator Bmal1 in mesenchymal cells leads to progressive osteochondral abnormalities in TMJ condyles, including disrupted cartilage stratification, thinning of the cartilage layer, and abnormal subchondral bone architecture, resembling age-related TMJ degeneration. Mechanistically, BMAL1 directly regulates Prg4 transcription, suppresses aberrant transforming growth factor β (TGF-β) signaling to maintain osteochondral homeostasis, and preserves the circadian rhythmicity of lipid metabolism. Notably, circadian-timed intra-articular administration of recombinant PRG4 at night, corresponding to its physiological expression peak, partially restores the cartilage integrity in both Bmal1 mutant and aged mice. Collectively, our findings reveal a mesenchymal clock-driven PRG4–TGF-β signaling axis that integrates circadian regulation with osteochondral homeostasis while also linking lipid metabolism, establishing chronotherapeutic PRG4 supplementation as a potential strategy to mitigate age-associated TMJ degeneration.
{"title":"Mesenchymal Clock Regulates TMJ Homeostasis and Lipid Metabolic Rhythms with Age","authors":"S. Cha, W. Gao, J. Wang, Z. Tan, C. Zhou, Q. Zhao, D. Bai","doi":"10.1177/00220345251401502","DOIUrl":"https://doi.org/10.1177/00220345251401502","url":null,"abstract":"Osteoarthritis (OA) is the most prevalent degenerative disorder of the temporomandibular joint (TMJ), with aging as a major risk factor. Although circadian clocks are essential for maintaining tissue homeostasis and metabolic balance, the influence of aging on tissue-specific circadian regulation of TMJ homeostasis remains unclear. Here, using aged mice and transgenic mouse models, we demonstrated that the mesenchymal circadian clock is indispensable for preserving TMJ osteochondral integrity during aging. Loss of the core circadian regulator <jats:italic toggle=\"yes\">Bmal1</jats:italic> in mesenchymal cells leads to progressive osteochondral abnormalities in TMJ condyles, including disrupted cartilage stratification, thinning of the cartilage layer, and abnormal subchondral bone architecture, resembling age-related TMJ degeneration. Mechanistically, BMAL1 directly regulates <jats:italic toggle=\"yes\">Prg4</jats:italic> transcription, suppresses aberrant transforming growth factor β (TGF-β) signaling to maintain osteochondral homeostasis, and preserves the circadian rhythmicity of lipid metabolism. Notably, circadian-timed intra-articular administration of recombinant PRG4 at night, corresponding to its physiological expression peak, partially restores the cartilage integrity in both <jats:italic toggle=\"yes\">Bmal1</jats:italic> mutant and aged mice. Collectively, our findings reveal a mesenchymal clock-driven PRG4–TGF-β signaling axis that integrates circadian regulation with osteochondral homeostasis while also linking lipid metabolism, establishing chronotherapeutic PRG4 supplementation as a potential strategy to mitigate age-associated TMJ degeneration.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"22 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770750","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 : 2025-12-17DOI: 10.1177/00220345251391189
J. Markeli, S. Listl
Access to affordable oral health care is central to achieving universal health coverage. While out-of-pocket expenditures can pose particular challenges for older population groups, little is known about catastrophic oral health expenditures (COHE) among people aged ≥50 y. The present study aimed to identify the extent and variation of COHE for persons aged ≥50 y from 12 European countries, for which dental expenditure data were available from the seventh wave of the Survey of Health, Ageing and Retirement in Europe. Specifically, information from 77,261 persons was included in the analysis. According to World Health Organization definitions, COHEs were calculated as out-of-pocket dental spendings exceeding 40% of the net total household expenditure on basic needs (ie, food, housing, and utilities). Descriptive and regression analyses were applied to test if COHEs at age ≥50 y differ across countries or regions and do not vary by demographic characteristics (age, gender, education, marital status, household size). On average across countries, >2.27% of study participants were identified to have COHE, with the highest observed population proportion of COHE in Spain (10.95%) and the lowest in Sweden (0.12%). Older age was associated with a significantly higher likelihood of experiencing COHE: the risk of people aged ≥70 y (2.6%) was significantly higher than for people aged 50 to 60 y (1.7%). There was a significant difference in COHE between males (1.7%) and females (2.6%). This study is the first to identify the extent and differences in COHE among people aged ≥50 y in European countries. Out-of-pocket oral health expenditures detrimentally affect older adults, with unequitable variations by gender, age, and country/region of residence. These findings are pivotal for policy makers to inform strategies to achieve equity in access to affordable oral health care.
{"title":"Catastrophic Oral Health Expenditures among Europeans Aged 50 y and Older","authors":"J. Markeli, S. Listl","doi":"10.1177/00220345251391189","DOIUrl":"https://doi.org/10.1177/00220345251391189","url":null,"abstract":"Access to affordable oral health care is central to achieving universal health coverage. While out-of-pocket expenditures can pose particular challenges for older population groups, little is known about catastrophic oral health expenditures (COHE) among people aged ≥50 y. The present study aimed to identify the extent and variation of COHE for persons aged ≥50 y from 12 European countries, for which dental expenditure data were available from the seventh wave of the Survey of Health, Ageing and Retirement in Europe. Specifically, information from 77,261 persons was included in the analysis. According to World Health Organization definitions, COHEs were calculated as out-of-pocket dental spendings exceeding 40% of the net total household expenditure on basic needs (ie, food, housing, and utilities). Descriptive and regression analyses were applied to test if COHEs at age ≥50 y differ across countries or regions and do not vary by demographic characteristics (age, gender, education, marital status, household size). On average across countries, >2.27% of study participants were identified to have COHE, with the highest observed population proportion of COHE in Spain (10.95%) and the lowest in Sweden (0.12%). Older age was associated with a significantly higher likelihood of experiencing COHE: the risk of people aged ≥70 y (2.6%) was significantly higher than for people aged 50 to 60 y (1.7%). There was a significant difference in COHE between males (1.7%) and females (2.6%). This study is the first to identify the extent and differences in COHE among people aged ≥50 y in European countries. Out-of-pocket oral health expenditures detrimentally affect older adults, with unequitable variations by gender, age, and country/region of residence. These findings are pivotal for policy makers to inform strategies to achieve equity in access to affordable oral health care.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"17 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765078","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 : 2025-12-17DOI: 10.1177/00220345251397364
C. Yanez, Z. Sarroukh, S. Listl
{"title":"Disability Weights for Orofacial Pain","authors":"C. Yanez, Z. Sarroukh, S. Listl","doi":"10.1177/00220345251397364","DOIUrl":"https://doi.org/10.1177/00220345251397364","url":null,"abstract":"","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"27 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765081","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 : 2025-12-17DOI: 10.1177/00220345251391194
R. Naamneh, F.L. Shoukair, M. Gera, Y. Jaber, S. Yacoub, Y. Netanely, Y. Saba, K. Zubeidat, A. Wilensky, I. Prinz, N. Casap, A.H. Hovav
Bone fracture healing requires coordinated interactions between immune cells and skeletal tissues, with flat bones exhibiting unique biomechanical and physiologic characteristics as compared with long bones. The mandible, the lower jawbone that supports the oral cavity, has distinct features due to its proximity to the oral mucosa, which is enriched in immune cells and microbiota, and its exposure to masticatory forces, making it a clinically relevant model for studying immune–skeletal interactions during fracture repair. Moreover, mandibular fractures are common maxillofacial injuries, posing challenges owing to functional and aesthetic considerations, as well as the risk of infection and impaired healing. Recent studies have highlighted conflicting roles for interleukin 17 (IL-17) and γδT cells in bone fracture or defect healing. As the primary source of IL-17 in the oral mucosa, γδT cells play a critical role in alveolar bone remodeling and respond to environmental factors such as the microbiota and age. We thus sought to investigate their role in the repair process of a mandibular defect. Here, we developed a murine model where a 1.5-mm drill hole defect spontaneously healed within 3 wk. Analysis revealed rapid leukocyte infiltration at the defect site by day 3, predominantly neutrophils and inflammatory monocytes, with γδT cells and adaptive leukocytes accumulating later at days 7 and 14. Depletion of γδT cells via Tcrd-GDL mice or genetic ablation of IL-17 in Il17af-/- mice accelerated the kinetics of mandibular healing. Bulk RNA sequencing and immunologic analysis revealed that while early recruitment of neutrophils and monocytes was unaffected in Il17af-/- mice, later inflammatory responses were diminished, resulting in accelerated repair. These findings suggest that IL-17–producing γδT cells (γδ17T cells) delay mandibular fracture repair by inhibiting inflammation resolution, thus prolonging the reparative phase. Targeting γδ17T cells or IL-17 may thus represent therapeutic strategies to enhance bone regeneration, particularly in challenging clinical settings involving mandibular fractures.
{"title":"γδ17T Cells Hinder Mandibular Bone Defect Healing","authors":"R. Naamneh, F.L. Shoukair, M. Gera, Y. Jaber, S. Yacoub, Y. Netanely, Y. Saba, K. Zubeidat, A. Wilensky, I. Prinz, N. Casap, A.H. Hovav","doi":"10.1177/00220345251391194","DOIUrl":"https://doi.org/10.1177/00220345251391194","url":null,"abstract":"Bone fracture healing requires coordinated interactions between immune cells and skeletal tissues, with flat bones exhibiting unique biomechanical and physiologic characteristics as compared with long bones. The mandible, the lower jawbone that supports the oral cavity, has distinct features due to its proximity to the oral mucosa, which is enriched in immune cells and microbiota, and its exposure to masticatory forces, making it a clinically relevant model for studying immune–skeletal interactions during fracture repair. Moreover, mandibular fractures are common maxillofacial injuries, posing challenges owing to functional and aesthetic considerations, as well as the risk of infection and impaired healing. Recent studies have highlighted conflicting roles for interleukin 17 (IL-17) and γδT cells in bone fracture or defect healing. As the primary source of IL-17 in the oral mucosa, γδT cells play a critical role in alveolar bone remodeling and respond to environmental factors such as the microbiota and age. We thus sought to investigate their role in the repair process of a mandibular defect. Here, we developed a murine model where a 1.5-mm drill hole defect spontaneously healed within 3 wk. Analysis revealed rapid leukocyte infiltration at the defect site by day 3, predominantly neutrophils and inflammatory monocytes, with γδT cells and adaptive leukocytes accumulating later at days 7 and 14. Depletion of γδT cells via <jats:italic toggle=\"yes\">Tcrd-GDL</jats:italic> mice or genetic ablation of IL-17 in <jats:italic toggle=\"yes\">Il17af</jats:italic> <jats:sup>-/-</jats:sup> mice accelerated the kinetics of mandibular healing. Bulk RNA sequencing and immunologic analysis revealed that while early recruitment of neutrophils and monocytes was unaffected in <jats:italic toggle=\"yes\">Il17af</jats:italic> <jats:sup>-/-</jats:sup> mice, later inflammatory responses were diminished, resulting in accelerated repair. These findings suggest that IL-17–producing γδT cells (γδ17T cells) delay mandibular fracture repair by inhibiting inflammation resolution, thus prolonging the reparative phase. Targeting γδ17T cells or IL-17 may thus represent therapeutic strategies to enhance bone regeneration, particularly in challenging clinical settings involving mandibular fractures.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"20 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765080","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 : 2025-12-09DOI: 10.1177/00220345251392891
M L Chin,Z Li,G G Madureira,Y Zhang
Despite being introduced into restorative dentistry nearly 30 y ago and having evolved into the most widely used ceramic restorative system, zirconia has only recently become available for chairside, same-day treatments, thanks to the development of high-speed sintering technology. However, recent studies have revealed that high-speed sintering not only severely compromises the translucency of dental zirconias (particularly in 3YSZ and 5YSZ) but also alters the translucency hierarchy among these compositions. Building on these critical findings, we hypothesized that a composition between 3YSZ and 4YSZ, such as 3.5YSZ, may be better suited for high-speed sintering protocols, offering both excellent strength and translucency. To test this hypothesis, 30 disc-shaped 3.5YSZ were uniaxially pressed, followed by cold-isostatic pressing and bisque firing. These presintered discs were then subjected to high-speed sintering using a commercial 18-min zirconia speed-fire protocol. Translucency parameters (TP and TP00; n = 18), contrast ratio (CR; n = 18), and biaxial flexural strength (n = 18) tests were conducted, along with density (n = 10), microstructural (n = 3), and compositional (n = 3) characterizations. Our findings show that high-speed sintered 3.5YSZ exhibited superior TP and CR values (P < 0.0001) compared to existing YSZ counterparts, while maintaining the high-strength characteristic of 3YSZ (P = 0.7420). The clinical implications of this newly developed composition, as well as future directions for fabricating this material with improved translucency and strength for efficient chairside workflows, are discussed.
尽管近30年前被引入修复牙科，并已发展成为最广泛使用的陶瓷修复系统，但由于高速烧结技术的发展，氧化锆直到最近才可用于椅子旁的当日治疗。然而，最近的研究表明，高速烧结不仅严重损害了牙科氧化锆（特别是3YSZ和5YSZ）的半透明性，而且改变了这些成分之间的半透明等级。基于这些关键发现，我们假设介于3YSZ和4YSZ之间的成分，如3.5YSZ，可能更适合高速烧结方案，同时提供出色的强度和半透明性。为了验证这一假设，我们对30个圆盘形的3.5YSZ进行单轴挤压，然后进行冷等静压和浓汤烧制。然后使用商用的18分钟氧化锆速烧方案对这些预印光盘进行高速烧结。进行了半透明参数（TP和TP00， n = 18）、对比度（CR, n = 18）和双轴抗弯强度（n = 18）测试，以及密度（n = 10）、微观结构（n = 3）和成分（n = 3）表征。研究结果表明，高速烧结3.5YSZ在保持3YSZ高强度特性的同时，其TP和CR值均优于现有的同类材料（P < 0.0001）。本文讨论了这种新开发的组合物的临床意义，以及制造这种材料的未来方向，该材料具有改进的半透明性和强度，可用于有效的椅子边工作流程。
{"title":"A Novel Zirconia Composition for Speed Sintering with Enhanced Properties.","authors":"M L Chin,Z Li,G G Madureira,Y Zhang","doi":"10.1177/00220345251392891","DOIUrl":"https://doi.org/10.1177/00220345251392891","url":null,"abstract":"Despite being introduced into restorative dentistry nearly 30 y ago and having evolved into the most widely used ceramic restorative system, zirconia has only recently become available for chairside, same-day treatments, thanks to the development of high-speed sintering technology. However, recent studies have revealed that high-speed sintering not only severely compromises the translucency of dental zirconias (particularly in 3YSZ and 5YSZ) but also alters the translucency hierarchy among these compositions. Building on these critical findings, we hypothesized that a composition between 3YSZ and 4YSZ, such as 3.5YSZ, may be better suited for high-speed sintering protocols, offering both excellent strength and translucency. To test this hypothesis, 30 disc-shaped 3.5YSZ were uniaxially pressed, followed by cold-isostatic pressing and bisque firing. These presintered discs were then subjected to high-speed sintering using a commercial 18-min zirconia speed-fire protocol. Translucency parameters (TP and TP00; n = 18), contrast ratio (CR; n = 18), and biaxial flexural strength (n = 18) tests were conducted, along with density (n = 10), microstructural (n = 3), and compositional (n = 3) characterizations. Our findings show that high-speed sintered 3.5YSZ exhibited superior TP and CR values (P < 0.0001) compared to existing YSZ counterparts, while maintaining the high-strength characteristic of 3YSZ (P = 0.7420). The clinical implications of this newly developed composition, as well as future directions for fabricating this material with improved translucency and strength for efficient chairside workflows, are discussed.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"239 1","pages":"220345251392891"},"PeriodicalIF":7.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710899","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 : 2025-12-09DOI: 10.1177/00220345251388914
W. Thompson, A. Al-Ahmad, F. Cieplik, A. Hbibi, N.S. Jakubovics, K.J. Scholz, L. Teoh, M. Charles-Ayinde, C.H. Fox
Antimicrobial resistance (AMR) poses an urgent global health threat, with significant implications for dentistry, which accounts for an estimated 10% of global antibiotic prescriptions. In response, the International Association for Dental, Oral, and Craniofacial Research (IADR) developed a new policy statement recognizing the critical role of oral health professionals and research in addressing AMR. This statement, adopted at the 103rd IADR General Session, highlights the misuse and overuse of antibiotics and antiseptics in dental settings and underscores the role of the oral microbiome as a potential AMR gene reservoir. Drawing on World Health Organization priorities, it outlines key research areas across prevention, diagnosis, treatment, health systems, environmental surveillance, and gender equity. The IADR calls for integrated, evidence-based approaches to antimicrobial stewardship, emphasizing the need for improved diagnostics, context-specific interventions, and cross-sectoral collaboration. This policy reinforces IADR’s commitment to advancing science-based solutions to preserve antimicrobial efficacy and promote global oral and public health.
{"title":"The IADR Policy Statement on Antimicrobial Resistance","authors":"W. Thompson, A. Al-Ahmad, F. Cieplik, A. Hbibi, N.S. Jakubovics, K.J. Scholz, L. Teoh, M. Charles-Ayinde, C.H. Fox","doi":"10.1177/00220345251388914","DOIUrl":"https://doi.org/10.1177/00220345251388914","url":null,"abstract":"Antimicrobial resistance (AMR) poses an urgent global health threat, with significant implications for dentistry, which accounts for an estimated 10% of global antibiotic prescriptions. In response, the International Association for Dental, Oral, and Craniofacial Research (IADR) developed a new policy statement recognizing the critical role of oral health professionals and research in addressing AMR. This statement, adopted at the 103rd IADR General Session, highlights the misuse and overuse of antibiotics and antiseptics in dental settings and underscores the role of the oral microbiome as a potential AMR gene reservoir. Drawing on World Health Organization priorities, it outlines key research areas across prevention, diagnosis, treatment, health systems, environmental surveillance, and gender equity. The IADR calls for integrated, evidence-based approaches to antimicrobial stewardship, emphasizing the need for improved diagnostics, context-specific interventions, and cross-sectoral collaboration. This policy reinforces IADR’s commitment to advancing science-based solutions to preserve antimicrobial efficacy and promote global oral and public health.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"34 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704199","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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