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}
Pub Date : 2025-12-09DOI: 10.1177/00220345251398027
A Orlenko,J D Mure,J I Gluch,J Gregg,C W Compher,Z Ren,H Koo,J H Moore
National Health and Nutrition Examination Survey (NHANES), one of the largest curated repositories of population-level health indicators including physical examinations, blood/urine biochemistry, self-reported surveys, and dietary intake, offers rich resources for oral health research but presents challenges for machine learning analysis due to heterogeneity, missing data, and complexity. Dental caries, the most prevalent chronic disease worldwide, is a multifactorial disease and exhibits variability in clinical manifestation, calling for advanced analytical approaches for deeper understanding. Here, we develop an integrated data-cleaning and subtype discovery pipeline using unsupervised machine learning for comprehensive analysis and visualization of data patterns in the NHANES database. Our multidimensional pipeline declutters and optimizes the NHANES dataset by addressing missingness and outliers to streamline data integration and create a machine learning-ready version. Applying this pipeline reveals data patterns that led to the discovery of previously unrecognized subtypes and variables associated with the clinical heterogeneity of dental caries. We observed diverging patterns of similarity across age groups and variable subsets, identifying distinct clusters particularly in children (<5 y) and senior adults (>65 y). We also discovered unexpected associations involving lead exposure and specific laboratory markers and, importantly, identified novel dietary signatures by linking food type and co-occurring consumption patterns to caries. Altogether, we report a comprehensive data-processing and data-analysis approach that reveals significant dental caries heterogeneity in NHANES data and can support the development of more precise and robust machine learning models for dental caries and other health conditions.
{"title":"Uncovering Dental Caries Heterogeneity in NHANES Using Machine Learning.","authors":"A Orlenko,J D Mure,J I Gluch,J Gregg,C W Compher,Z Ren,H Koo,J H Moore","doi":"10.1177/00220345251398027","DOIUrl":"https://doi.org/10.1177/00220345251398027","url":null,"abstract":"National Health and Nutrition Examination Survey (NHANES), one of the largest curated repositories of population-level health indicators including physical examinations, blood/urine biochemistry, self-reported surveys, and dietary intake, offers rich resources for oral health research but presents challenges for machine learning analysis due to heterogeneity, missing data, and complexity. Dental caries, the most prevalent chronic disease worldwide, is a multifactorial disease and exhibits variability in clinical manifestation, calling for advanced analytical approaches for deeper understanding. Here, we develop an integrated data-cleaning and subtype discovery pipeline using unsupervised machine learning for comprehensive analysis and visualization of data patterns in the NHANES database. Our multidimensional pipeline declutters and optimizes the NHANES dataset by addressing missingness and outliers to streamline data integration and create a machine learning-ready version. Applying this pipeline reveals data patterns that led to the discovery of previously unrecognized subtypes and variables associated with the clinical heterogeneity of dental caries. We observed diverging patterns of similarity across age groups and variable subsets, identifying distinct clusters particularly in children (<5 y) and senior adults (>65 y). We also discovered unexpected associations involving lead exposure and specific laboratory markers and, importantly, identified novel dietary signatures by linking food type and co-occurring consumption patterns to caries. Altogether, we report a comprehensive data-processing and data-analysis approach that reveals significant dental caries heterogeneity in NHANES data and can support the development of more precise and robust machine learning models for dental caries and other health conditions.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"29 1","pages":"220345251398027"},"PeriodicalIF":7.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704377","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: 10.1177/00220345251388919
M S Rahman,A Martinez,H W Elani
Access to general dental care remains a widespread challenge in the United States. In addition, many oral health conditions require treatment by dental specialists. Little is known about the geographic distribution and accessibility of these providers, particularly in rural areas. A national, block group-level analysis of geographic access to 6 core dental specialties-endodontics, oral and maxillofacial surgery, orthodontics, pediatric dentistry, periodontics, and prosthodontics-was conducted. The provider locations from a 2023 national database of practicing dental specialists (N = 38,698) were geocoded. An enhanced 2-step floating catchment area model was applied to generate spatial accessibility scores and drive-time estimates from population-weighted centers. The analysis of these data showed that on average, more than one-third of the US population had adequate access to specialty clinics, while less than 15% resided more than 30 min away from these specialists. Adequate accessibility was highest for orthodontics (61.6%, n = 204.1 million) and lowest for prosthodontics (6.7%, n = 22.2). Rural residents faced average driving times 3.2 times longer than urban residents do. The disparity was most severe in states such as Alaska, Montana, Nevada, North Dakota, South Dakota, and Wyoming, where driving times to specialists often exceeded an hour. More than 98% of dental specialists practice in urban areas, leaving rural regions consistently underserved. These findings indicate pronounced and widespread geographic disparities in access to dental specialists across the United States, driven by geographic concentration in metropolitan areas. These gaps have serious implications for access to timely diagnoses, treatment quality, and oral health-related quality of life. Workforce policies must expand beyond general dentistry to address dental specialty shortages. Integrating dental specialists into shortage designations, loan repayment programs, and training pipelines is essential for achieving equitable access to comprehensive oral health care nationwide.
{"title":"Geographic Access to Dental Specialists in the United States.","authors":"M S Rahman,A Martinez,H W Elani","doi":"10.1177/00220345251388919","DOIUrl":"https://doi.org/10.1177/00220345251388919","url":null,"abstract":"Access to general dental care remains a widespread challenge in the United States. In addition, many oral health conditions require treatment by dental specialists. Little is known about the geographic distribution and accessibility of these providers, particularly in rural areas. A national, block group-level analysis of geographic access to 6 core dental specialties-endodontics, oral and maxillofacial surgery, orthodontics, pediatric dentistry, periodontics, and prosthodontics-was conducted. The provider locations from a 2023 national database of practicing dental specialists (N = 38,698) were geocoded. An enhanced 2-step floating catchment area model was applied to generate spatial accessibility scores and drive-time estimates from population-weighted centers. The analysis of these data showed that on average, more than one-third of the US population had adequate access to specialty clinics, while less than 15% resided more than 30 min away from these specialists. Adequate accessibility was highest for orthodontics (61.6%, n = 204.1 million) and lowest for prosthodontics (6.7%, n = 22.2). Rural residents faced average driving times 3.2 times longer than urban residents do. The disparity was most severe in states such as Alaska, Montana, Nevada, North Dakota, South Dakota, and Wyoming, where driving times to specialists often exceeded an hour. More than 98% of dental specialists practice in urban areas, leaving rural regions consistently underserved. These findings indicate pronounced and widespread geographic disparities in access to dental specialists across the United States, driven by geographic concentration in metropolitan areas. These gaps have serious implications for access to timely diagnoses, treatment quality, and oral health-related quality of life. Workforce policies must expand beyond general dentistry to address dental specialty shortages. Integrating dental specialists into shortage designations, loan repayment programs, and training pipelines is essential for achieving equitable access to comprehensive oral health care nationwide.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"140 1","pages":"220345251388919"},"PeriodicalIF":7.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710896","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 : 2025-12-08DOI: 10.1177/00220345251388641
S Wang,W Kang,D Wang,X Liu,J Feng,T Wang,W Zhao,J Li,S Ge
Periodontitis is a chronic inflammatory disease characterized by a dysregulated interaction between the subgingival microbiota and the host immune response, leading to the accumulation of excessive inflammatory mediators and progressive tissue destruction. In this study, we first established a correlation between polyamine accumulation and periodontal inflammation by testing clinical samples of gingival crevicular fluid. To test the hypothesis that polyamine scavenging will benefit periodontitis treatment, we developed a polyamine-capturing hydrogel loaded with charge modified dodecyl sulfobutyl ether-β-cyclodextrin (SCDC12). The self-assembled SCDC12 nanoparticles effectively alleviated the cellular oxidative stress, improved cell viability, and inhibited the expression of proinflammatory factors by capturing polyamines in vitro. In addition, SCDC12 inhibited the growth of periodontal pathogens and biofilm formation. In a rat periodontitis model, SCDC12 hydrogel inhibited the expression of the rate-limiting enzyme in polyamine anabolism, downregulated the level of proinflammatory factors, and reduced local inflammatory response and alveolar bone loss. Our findings highlight SCDC12 as a promising polyamine scavenger, offering a novel therapeutic strategy for periodontitis treatment by restoring polyamine homeostasis.
{"title":"A Polyamine-Capturing Cyclodextrin Hydrogel for Periodontitis Treatment.","authors":"S Wang,W Kang,D Wang,X Liu,J Feng,T Wang,W Zhao,J Li,S Ge","doi":"10.1177/00220345251388641","DOIUrl":"https://doi.org/10.1177/00220345251388641","url":null,"abstract":"Periodontitis is a chronic inflammatory disease characterized by a dysregulated interaction between the subgingival microbiota and the host immune response, leading to the accumulation of excessive inflammatory mediators and progressive tissue destruction. In this study, we first established a correlation between polyamine accumulation and periodontal inflammation by testing clinical samples of gingival crevicular fluid. To test the hypothesis that polyamine scavenging will benefit periodontitis treatment, we developed a polyamine-capturing hydrogel loaded with charge modified dodecyl sulfobutyl ether-β-cyclodextrin (SCDC12). The self-assembled SCDC12 nanoparticles effectively alleviated the cellular oxidative stress, improved cell viability, and inhibited the expression of proinflammatory factors by capturing polyamines in vitro. In addition, SCDC12 inhibited the growth of periodontal pathogens and biofilm formation. In a rat periodontitis model, SCDC12 hydrogel inhibited the expression of the rate-limiting enzyme in polyamine anabolism, downregulated the level of proinflammatory factors, and reduced local inflammatory response and alveolar bone loss. Our findings highlight SCDC12 as a promising polyamine scavenger, offering a novel therapeutic strategy for periodontitis treatment by restoring polyamine homeostasis.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"6 1","pages":"220345251388641"},"PeriodicalIF":7.6,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704378","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 : 2025-12-06DOI: 10.1177/00220345251379445
K.D. Cox, M. Makara, J.O. Maldonado, J. Frantsve-Hawley, S. E. Carsons, V. Sankar
Sjögren’s disease (SjD) exemplifies the intricate relationship between oral health and overall systemic wellness. Characterized by autoimmune-mediated destruction of exocrine glands, it commonly manifests as xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes), yet its reach extends well beyond the salivary and lacrimal glands to involve musculoskeletal, renal, pulmonary, and neurological systems. Insights from national patient surveys underscore considerable unmet needs in SjD management, emphasizing the importance of early recognition of oral health challenges. Concurrently, advances in clinical and translational research deepen our understanding of SjD’s underlying mechanisms, revealing novel diagnostic and therapeutic strategies that target immunological pathways, foster glandular regeneration, and may alter disease progression. By providing a cohesive synthesis of state-of-the-art evidence, this review aims to expand clinicians’ and researchers’ understanding of SjD pathogenesis, address new research areas and key gaps, highlight the critical role of medical partnerships in addressing both systemic and oral manifestations, and advance patient-centered strategies to improve detection, treatment, and long-term disease management of this multifaceted autoimmune disorder. We discuss immune-mediated tissue damage, the potential of emerging biomarkers, and innovative treatments, including biologic agents and regenerative techniques. Patient perspectives further illuminate the daily challenges posed by SjD, underscoring the need for interdisciplinary care models that integrate oral medicine, rheumatology, and other medical specialties. Taken together, these insights underscore the pressing need for heightened awareness and collaborative approaches to pave the way for precision medicine interventions that can transform current management paradigms and ultimately improve the lives of individuals affected by Sjögren’s disease.
{"title":"Exploring the Interplay of Oral and Systemic Pathology in Sjögren’s Disease","authors":"K.D. Cox, M. Makara, J.O. Maldonado, J. Frantsve-Hawley, S. E. Carsons, V. Sankar","doi":"10.1177/00220345251379445","DOIUrl":"https://doi.org/10.1177/00220345251379445","url":null,"abstract":"Sjögren’s disease (SjD) exemplifies the intricate relationship between oral health and overall systemic wellness. Characterized by autoimmune-mediated destruction of exocrine glands, it commonly manifests as xerostomia (dry mouth) and keratoconjunctivitis sicca (dry eyes), yet its reach extends well beyond the salivary and lacrimal glands to involve musculoskeletal, renal, pulmonary, and neurological systems. Insights from national patient surveys underscore considerable unmet needs in SjD management, emphasizing the importance of early recognition of oral health challenges. Concurrently, advances in clinical and translational research deepen our understanding of SjD’s underlying mechanisms, revealing novel diagnostic and therapeutic strategies that target immunological pathways, foster glandular regeneration, and may alter disease progression. By providing a cohesive synthesis of state-of-the-art evidence, this review aims to expand clinicians’ and researchers’ understanding of SjD pathogenesis, address new research areas and key gaps, highlight the critical role of medical partnerships in addressing both systemic and oral manifestations, and advance patient-centered strategies to improve detection, treatment, and long-term disease management of this multifaceted autoimmune disorder. We discuss immune-mediated tissue damage, the potential of emerging biomarkers, and innovative treatments, including biologic agents and regenerative techniques. Patient perspectives further illuminate the daily challenges posed by SjD, underscoring the need for interdisciplinary care models that integrate oral medicine, rheumatology, and other medical specialties. Taken together, these insights underscore the pressing need for heightened awareness and collaborative approaches to pave the way for precision medicine interventions that can transform current management paradigms and ultimately improve the lives of individuals affected by Sjögren’s disease.","PeriodicalId":15596,"journal":{"name":"Journal of Dental Research","volume":"26 1","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680106","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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