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}
The development of caries management materials has concentrated on the dual objectives of inhibiting cariogenic microorganisms and promoting remineralization. In this study, 2 dual-functional ionic liquid (IL) varnishes, exhibiting both antibacterial and remineralization capabilities, were synthesized as novel anticaries agents. The ionic liquids (ILs) were prepared by modifying 1-hexylimidazolium IL with 3-chloropropyltriethoxysilane, followed by anion exchange with F- and a coordination reaction with Sr2+, respectively. The ILs were characterized using energy-dispersive spectroscopy (EDS), ion chromatography (IC), inductively coupled plasma optical emission spectrometry (ICP-OES), and Fourier transform infrared spectroscopy (FTIR). The antibacterial efficacy of the ILs was evaluated through colony counting, live/dead staining, and scanning electron microscopy (SEM). Subsequently, the ILs were blended with rosin to form IL varnishes. The remineralization potential of the IL varnishes was assessed through microhardness test, acid resistance test, SEM, EDS, and X-ray diffraction. In addition, in vivo anticaries treatment with the IL varnishes was conducted using a dental caries animal model. Histopathological and oral microbiome analyses were performed to evaluate the in vivo biocompatibility of the materials. The comprehensive analysis by EDS, IC, ICP-OES, and FTIR collectively confirmed the successful synthesis of the ILs. Antibacterial assays revealed that ILs at concentrations as low as 25 µM eliminated more than 80% of cariogenic bacteria within 60 min and significantly decreased viable bacteria in biofilms within 24 h. Following a 7-d treatment with the IL varnishes, SEM analysis of acid-etched enamel demonstrated reduced interspace depth, along with substantially increased microhardness and significantly improved acid resistance versus the negative control group. As compared with the fluoride varnish, the IL varnishes are more effective in preventing dental caries in rats, without harming oral buccal mucosa, major organs, or microbiota diversity. In conclusion, the IL varnishes developed in this study are not only straightforward to synthesize but also exhibit significant potential against dental caries.
{"title":"Dual-Functional Ionic Liquid Varnishes for Dental Caries Management.","authors":"H-W Chen,Y-F Yuan,C-L Wang,D-Y Wang,Z-C Zhou,L Fan,Q-X Zhang,Y-N He,W-K Jiang,S-C Wang","doi":"10.1177/00220345251397916","DOIUrl":"https://doi.org/10.1177/00220345251397916","url":null,"abstract":"The development of caries management materials has concentrated on the dual objectives of inhibiting cariogenic microorganisms and promoting remineralization. In this study, 2 dual-functional ionic liquid (IL) varnishes, exhibiting both antibacterial and remineralization capabilities, were synthesized as novel anticaries agents. The ionic liquids (ILs) were prepared by modifying 1-hexylimidazolium IL with 3-chloropropyltriethoxysilane, followed by anion exchange with F- and a coordination reaction with Sr2+, respectively. The ILs were characterized using energy-dispersive spectroscopy (EDS), ion chromatography (IC), inductively coupled plasma optical emission spectrometry (ICP-OES), and Fourier transform infrared spectroscopy (FTIR). The antibacterial efficacy of the ILs was evaluated through colony counting, live/dead staining, and scanning electron microscopy (SEM). Subsequently, the ILs were blended with rosin to form IL varnishes. The remineralization potential of the IL varnishes was assessed through microhardness test, acid resistance test, SEM, EDS, and X-ray diffraction. In addition, in vivo anticaries treatment with the IL varnishes was conducted using a dental caries animal model. Histopathological and oral microbiome analyses were performed to evaluate the in vivo biocompatibility of the materials. The comprehensive analysis by EDS, IC, ICP-OES, and FTIR collectively confirmed the successful synthesis of the ILs. Antibacterial assays revealed that ILs at concentrations as low as 25 µM eliminated more than 80% of cariogenic bacteria within 60 min and significantly decreased viable bacteria in biofilms within 24 h. Following a 7-d treatment with the IL varnishes, SEM analysis of acid-etched enamel demonstrated reduced interspace depth, along with substantially increased microhardness and significantly improved acid resistance versus the negative control group. As compared with the fluoride varnish, the IL varnishes are more effective in preventing dental caries in rats, without harming oral buccal mucosa, major organs, or microbiota diversity. In conclusion, the IL varnishes developed in this study are not only straightforward to synthesize but also exhibit significant potential against dental caries.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"13 1","pages":"220345251397916"},"PeriodicalIF":7.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710897","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: 10.1177/00220345251394281
K M Desai,N A Tadkalkar,M Amin,R Kumar,S U Rahman,S Ponnusamy,P Angadi,W Liu,R V Dayani,A D Kale,J Slone,D Chandra,P R Arany
Cell survival, differentiation, and death are tightly regulated processes that maintain tissue homeostasis. Arecoline and transforming growth factor-beta (TGF-β) have been implicated as key mediators in oral submucous fibrosis (OSMF). The persistent, overactive fibroblasts in fibrotic lesions have altered metabolism and cytoskeletal changes. The present work evaluated the effects of arecoline and TGF-β on the mitochondrial bioenergetics and phenotype of oral fibroblasts. Human oral fibroblasts were treated with arecoline, TGF-β1, and combinations and evaluated for cell survival using AlamarBlue and vital staining. To assess mitochondrial fusion, MF18 inhibitor and OPA-1, MFN-2, and fission, Mdivi inhibitor and DRP-1 were used. Changes in cell responses were assessed with real-time quantitative polymerase chain reaction, immunofluorescence, and Seahorse analysis. Following institutional review board approval, archival human tissue biopsies from OSMF at various grades were evaluated for correlation with modulation of fibroblast metabolism and cytoskeletal changes. Arecoline-treated fibroblasts showed significant (n = 3, P < 0.05) cell death rescued by TGF-β1 treatments (n = 3, P < 0.05). Further examination revealed that arecoline-treated cells exhibited mitochondrial fission with a glycolytic (reduced transcription factor of mitochondria [TFAM], increased hexokinase II, n = 3, P < 0.05) metabolic profile and reduced OPA1 expression. In contrast, TGF-β1 treatments demonstrated mitochondrial fusion, accompanied by increased OPA1 expression. Combined treatments with arecoline and TGF-β1 demonstrated improved cell survival, reduced fission, and improved mitochondrial bioenergetics. These results correlated with increased TFAM and vimentin-actin (VA) expression, representing a synthetic, overactive fibroblast phenotype. Finally, clinical samples from patients with OSMF exhibited a progressive increase in TFAM and VA-positive fibroblasts in advanced clinical disease, corroborating the in vitro observations. TGF-β1 appears to modulate mitochondrial responses in arecoline-induced cytotoxicity, resulting in fibroblast survival, leading to a profibrotic phenotype. These observations suggest that selective targeting of the mitochondria driving these surviving myofibroblasts may serve as a novel therapeutic target for clinical translation.
细胞的存活、分化和死亡是维持组织稳态的严格调控过程。槟榔碱和转化生长因子β (TGF-β)被认为是口腔粘膜下纤维化（OSMF）的关键介质。纤维化病变中持续的、过度活跃的成纤维细胞改变了代谢和细胞骨架的变化。本研究探讨槟榔碱和TGF-β对口腔成纤维细胞线粒体生物能量学和表型的影响。用槟榔碱、TGF-β1和组合处理人口腔成纤维细胞，并使用AlamarBlue和vital染色评估细胞存活率。为了评估线粒体融合，使用MF18抑制剂和OPA-1， MFN-2，以及裂变，Mdivi抑制剂和DRP-1。通过实时定量聚合酶链反应、免疫荧光和海马分析来评估细胞反应的变化。在机构审查委员会批准后，评估了不同级别OSMF的档案人体组织活检与成纤维细胞代谢调节和细胞骨架变化的相关性。槟榔碱处理的成纤维细胞经TGF-β1处理后出现显著的细胞死亡（n = 3, P < 0.05）。进一步的研究表明，槟榔碱处理的细胞表现出线粒体分裂，糖酵解（线粒体转录因子[TFAM]减少，己糖激酶II增加，n = 3, P < 0.05）代谢谱和降低OPA1表达。相比之下，TGF-β1处理表现为线粒体融合，并伴有OPA1表达增加。槟榔碱和TGF-β1联合治疗可提高细胞存活率，减少裂变，改善线粒体生物能量学。这些结果与TFAM和vimentin-actin （VA）表达增加相关，代表了合成的、过度活跃的成纤维细胞表型。最后，来自OSMF患者的临床样本在晚期临床疾病中表现出TFAM和va阳性成纤维细胞的进行性增加，证实了体外观察。TGF-β1似乎在槟榔碱诱导的细胞毒性中调节线粒体反应，导致成纤维细胞存活，导致纤维化表型。这些观察结果表明，选择性靶向线粒体驱动这些存活的肌成纤维细胞可能作为临床翻译的新治疗靶点。
{"title":"TGF-β1 Directs TFAM-Mediated Mitochondrial Reprogramming in Oral Submucous Fibrosis.","authors":"K M Desai,N A Tadkalkar,M Amin,R Kumar,S U Rahman,S Ponnusamy,P Angadi,W Liu,R V Dayani,A D Kale,J Slone,D Chandra,P R Arany","doi":"10.1177/00220345251394281","DOIUrl":"https://doi.org/10.1177/00220345251394281","url":null,"abstract":"Cell survival, differentiation, and death are tightly regulated processes that maintain tissue homeostasis. Arecoline and transforming growth factor-beta (TGF-β) have been implicated as key mediators in oral submucous fibrosis (OSMF). The persistent, overactive fibroblasts in fibrotic lesions have altered metabolism and cytoskeletal changes. The present work evaluated the effects of arecoline and TGF-β on the mitochondrial bioenergetics and phenotype of oral fibroblasts. Human oral fibroblasts were treated with arecoline, TGF-β1, and combinations and evaluated for cell survival using AlamarBlue and vital staining. To assess mitochondrial fusion, MF18 inhibitor and OPA-1, MFN-2, and fission, Mdivi inhibitor and DRP-1 were used. Changes in cell responses were assessed with real-time quantitative polymerase chain reaction, immunofluorescence, and Seahorse analysis. Following institutional review board approval, archival human tissue biopsies from OSMF at various grades were evaluated for correlation with modulation of fibroblast metabolism and cytoskeletal changes. Arecoline-treated fibroblasts showed significant (n = 3, P < 0.05) cell death rescued by TGF-β1 treatments (n = 3, P < 0.05). Further examination revealed that arecoline-treated cells exhibited mitochondrial fission with a glycolytic (reduced transcription factor of mitochondria [TFAM], increased hexokinase II, n = 3, P < 0.05) metabolic profile and reduced OPA1 expression. In contrast, TGF-β1 treatments demonstrated mitochondrial fusion, accompanied by increased OPA1 expression. Combined treatments with arecoline and TGF-β1 demonstrated improved cell survival, reduced fission, and improved mitochondrial bioenergetics. These results correlated with increased TFAM and vimentin-actin (VA) expression, representing a synthetic, overactive fibroblast phenotype. Finally, clinical samples from patients with OSMF exhibited a progressive increase in TFAM and VA-positive fibroblasts in advanced clinical disease, corroborating the in vitro observations. TGF-β1 appears to modulate mitochondrial responses in arecoline-induced cytotoxicity, resulting in fibroblast survival, leading to a profibrotic phenotype. These observations suggest that selective targeting of the mitochondria driving these surviving myofibroblasts may serve as a novel therapeutic target for clinical translation.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"140 1","pages":"220345251394281"},"PeriodicalIF":7.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710734","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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