首页 > 最新文献

Journal of dental research最新文献

英文 中文
Genetically Supported Drug Targets and Dental Traits: A Mendelian Randomization Study. 基因支持药物靶点与牙齿特征:孟德尔随机化研究。
Pub Date : 2024-10-06 DOI: 10.1177/00220345241272045
L Liu, T Wang, C Duan, S Mao, B Wu, Y Chen, D Huang, Y Cao

Current interventions for oral/dental diseases heavily rely on operative/surgical procedures, while the discovery of novel drug targets may enable access to noninvasive pharmacotherapy. Therefore, this study aims to leverage large-scale data and Mendelian randomization (MR) techniques, utilizing genetic variants as instruments, to identify potential therapeutic targets for oral and dental diseases supported by genetic evidence. By intersecting 4,302 druggable genes with expression quantitative trait loci from 31,684 blood samples, we identified 2,580 druggable targets as exposures. Single nucleotide polymorphisms associated with dental disease/symptom traits were collected from FinnGen R9, the Gene-Lifestyle Interactions in Dental Endpoints consortium, and the UK Biobank to serve as outcomes for both discovery and replication purposes. Through MR analysis, we identified 43 druggable targets for various dental disease/symptom traits. To evaluate the viability of these targets, we replicated the analysis using circulating protein quantitative trait loci as exposures. Additionally, we conducted sensitivity, colocalization, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes annotation, protein-protein interaction analyses, and validated dental trait-associated druggable gene expression in animal models. Among these targets, IL12RB1 (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.01-1.01) and TNF (OR, 0.98; 95% CI, 0.97-0.99) exhibited therapeutic promise for oral ulcers, whereas CXCL10 (OR, 0.84; 95% CI, 0.76-0.91) was for periodontitis. Through a rigorous quality control and validation pipeline, our study yields compelling evidence for these druggable targets, which may enhance the clinical prognosis by developing novel drugs or repurposing existing ones.

目前对口腔/牙科疾病的干预在很大程度上依赖于手术/外科手术,而新型药物靶点的发现则可能使人们获得非侵入性的药物治疗。因此,本研究旨在利用大规模数据和孟德尔随机化(Mendelian randomization,MR)技术,以基因变异为工具,找出有基因证据支持的口腔和牙科疾病潜在治疗靶点。通过将 31,684 份血液样本中的 4,302 个可用药基因与表达定量性状位点相交叉,我们确定了 2,580 个可用药靶点作为暴露因子。与牙科疾病/症状特征相关的单核苷酸多态性是从 FinnGen R9、牙科终点基因与生活方式相互作用联盟和英国生物库中收集的,作为发现和复制的结果。通过磁共振分析,我们确定了 43 个可用于治疗各种牙科疾病/症状特征的靶点。为了评估这些靶点的可行性,我们使用循环蛋白定量性状位点作为暴露因子进行了重复分析。此外,我们还进行了灵敏度、共定位、基因本体/京都基因和基因组百科全书注释、蛋白-蛋白相互作用分析,并在动物模型中验证了与牙齿性状相关的可药用基因的表达。在这些靶点中,IL12RB1(几率比 [OR],1.01;95% 置信区间 [CI],1.01-1.01)和 TNF(OR,0.98;95% CI,0.97-0.99)对口腔溃疡有治疗前景,而 CXCL10(OR,0.84;95% CI,0.76-0.91)则对牙周炎有治疗前景。通过严格的质量控制和验证流程,我们的研究为这些可药用靶点提供了令人信服的证据,这些靶点可通过开发新型药物或重新利用现有药物来改善临床预后。
{"title":"Genetically Supported Drug Targets and Dental Traits: A Mendelian Randomization Study.","authors":"L Liu, T Wang, C Duan, S Mao, B Wu, Y Chen, D Huang, Y Cao","doi":"10.1177/00220345241272045","DOIUrl":"https://doi.org/10.1177/00220345241272045","url":null,"abstract":"<p><p>Current interventions for oral/dental diseases heavily rely on operative/surgical procedures, while the discovery of novel drug targets may enable access to noninvasive pharmacotherapy. Therefore, this study aims to leverage large-scale data and Mendelian randomization (MR) techniques, utilizing genetic variants as instruments, to identify potential therapeutic targets for oral and dental diseases supported by genetic evidence. By intersecting 4,302 druggable genes with expression quantitative trait loci from 31,684 blood samples, we identified 2,580 druggable targets as exposures. Single nucleotide polymorphisms associated with dental disease/symptom traits were collected from FinnGen R9, the Gene-Lifestyle Interactions in Dental Endpoints consortium, and the UK Biobank to serve as outcomes for both discovery and replication purposes. Through MR analysis, we identified 43 druggable targets for various dental disease/symptom traits. To evaluate the viability of these targets, we replicated the analysis using circulating protein quantitative trait loci as exposures. Additionally, we conducted sensitivity, colocalization, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes annotation, protein-protein interaction analyses, and validated dental trait-associated druggable gene expression in animal models. Among these targets, <i>IL12RB1</i> (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.01-1.01) and <i>TNF</i> (OR, 0.98; 95% CI, 0.97-0.99) exhibited therapeutic promise for oral ulcers, whereas <i>CXCL10</i> (OR, 0.84; 95% CI, 0.76-0.91) was for periodontitis. Through a rigorous quality control and validation pipeline, our study yields compelling evidence for these druggable targets, which may enhance the clinical prognosis by developing novel drugs or repurposing existing ones.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Therapeutic Use of Dental Mesenchymal Stem Cells in Human Clinical Trials. 牙间质干细胞在人类临床试验中的治疗用途。
Pub Date : 2024-10-06 DOI: 10.1177/00220345241261900
S Ivanovski, P Han, O A Peters, M Sanz, P M Bartold

Mesenchymal stem cells (MSCs), characterized by their undifferentiated and multipotent nature, can be derived from various sources, including bone marrow, adipose, and dental tissues. Among these, dental MSCs (DSCs) exhibit universal MSC characteristics and are attracting considerable attention for regenerating oral and craniofacial tissues. This review provides a contemporary overview of recently published clinical studies using DSCs for various orodental and maxillofacial regenerative applications, including bone, periodontal, and endodontic regeneration. It also explores the utilization of DSCs in treating systemic conditions, exemplified by their application in managing conditions such as COVID-19 and osteoarthritis. The available evidence underscores the potential of DSCs and their secretome as efficacious tools in regenerative medicine for both dental and nondental clinical applications, supporting the continued promise of stem cell-based therapies. It is nevertheless evident that there are a number of important challenges that restrict the widespread utilization of DSCs, namely, difficulty in standardizing autologous preparations, insufficient cell surface marker characterization, high production costs, and regulatory compliance requirements. Further, the unique requirements of dental applications, especially complex structures such as the periodontium, where temporospatial control over the healing process is required, necessitate the combination of stem cells with appropriate scaffolds according to the principles of tissue engineering. There is currently insufficient evidence to support the clinical translation of DSCs into clinical practice, and phase 3 clinical trials with standardized protocols for cell sourcing, propagation, dosing, and delivery are required to move the field forward. In summary, this review provides a contemporary overview of the evolving landscape of stem cell therapy, offering insights into the latest developments and trends as well as the challenges that need to be addressed for the widespread application of DSC-based cell therapies.

间充质干细胞(MSCs)具有未分化和多潜能的特点,可从骨髓、脂肪和牙科组织等各种来源获得。其中,牙科间充质干细胞(DSCs)具有间充质干细胞的普遍特征,在再生口腔和颅面组织方面备受关注。本综述概述了近期发表的将 DSCs 用于各种口腔和颌面部再生应用(包括骨、牙周和牙髓再生)的临床研究。报告还探讨了利用 DSCs 治疗全身性疾病的情况,例如 DSCs 在治疗 COVID-19 和骨关节炎等疾病中的应用。现有证据强调了DSCs及其分泌组作为再生医学有效工具在牙科和非牙科临床应用中的潜力,支持了干细胞疗法的持续前景。然而,很明显,有一些重要的挑战限制了干细胞的广泛应用,即自体制备难以标准化、细胞表面标记表征不足、生产成本高以及监管合规要求。此外,牙科应用的独特要求,特别是牙周等复杂结构,需要对愈合过程进行时间空间控制,因此必须根据组织工程学原理,将干细胞与适当的支架相结合。目前还没有足够的证据支持将干细胞转化为临床实践,需要进行第三阶段临床试验,并制定细胞来源、繁殖、剂量和输送的标准化方案,以推动该领域的发展。总之,这篇综述概述了干细胞疗法不断发展的现状,深入分析了最新的发展和趋势,以及广泛应用以DSC为基础的细胞疗法需要应对的挑战。
{"title":"The Therapeutic Use of Dental Mesenchymal Stem Cells in Human Clinical Trials.","authors":"S Ivanovski, P Han, O A Peters, M Sanz, P M Bartold","doi":"10.1177/00220345241261900","DOIUrl":"https://doi.org/10.1177/00220345241261900","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs), characterized by their undifferentiated and multipotent nature, can be derived from various sources, including bone marrow, adipose, and dental tissues. Among these, dental MSCs (DSCs) exhibit universal MSC characteristics and are attracting considerable attention for regenerating oral and craniofacial tissues. This review provides a contemporary overview of recently published clinical studies using DSCs for various orodental and maxillofacial regenerative applications, including bone, periodontal, and endodontic regeneration. It also explores the utilization of DSCs in treating systemic conditions, exemplified by their application in managing conditions such as COVID-19 and osteoarthritis. The available evidence underscores the potential of DSCs and their secretome as efficacious tools in regenerative medicine for both dental and nondental clinical applications, supporting the continued promise of stem cell-based therapies. It is nevertheless evident that there are a number of important challenges that restrict the widespread utilization of DSCs, namely, difficulty in standardizing autologous preparations, insufficient cell surface marker characterization, high production costs, and regulatory compliance requirements. Further, the unique requirements of dental applications, especially complex structures such as the periodontium, where temporospatial control over the healing process is required, necessitate the combination of stem cells with appropriate scaffolds according to the principles of tissue engineering. There is currently insufficient evidence to support the clinical translation of DSCs into clinical practice, and phase 3 clinical trials with standardized protocols for cell sourcing, propagation, dosing, and delivery are required to move the field forward. In summary, this review provides a contemporary overview of the evolving landscape of stem cell therapy, offering insights into the latest developments and trends as well as the challenges that need to be addressed for the widespread application of DSC-based cell therapies.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ALKBH5 Regulates Osteogenic Differentiation via the lncRNA/mRNA Complex. ALKBH5通过lncRNA/mRNA复合物调控成骨细胞分化
Pub Date : 2024-10-01 Epub Date: 2024-09-23 DOI: 10.1177/00220345241266775
Y Song, H Gao, Y Pan, Y Gu, W Sun, Y Wang, J Liu

Human adipose-derived stem cells (hASCs) are commonly used in bone tissue regeneration. The N6-methyladenosine (m6A) modification has emerged as a novel regulatory mechanism for gene expression, playing a critical role in osteogenic differentiation of stem cells. However, the precise role and mechanism of alkylation repair homolog 5 (ALKBH5) in hASC osteogenesis remain incompletely elucidated and warrant further investigation. Herein, we employed methylated RNA immunoprecipitation sequencing, RNA sequencing, and weighted gene coexpression network analysis to identify a key long noncoding RNA (lncRNA) in hASCs: lncRNA AK311120. Functional experiments demonstrated that lnc-AK311120 promoted the osteogenic differentiation of hASCs, while a mutation at the m6A central site A of lnc-AK311120 was found to decrease the level of m6A modification. The osteogenic effect of ALKBH5 was confirmed both in vitro and in vivo using a mandibular defect model in nude mice. Subsequent investigations revealed that knockdown of ALKBH5 resulted in a significant increase in the m6A modification level of lnc-AK311120, accompanied by a downregulation in the expression level of lnc-AK311120. Additional rescue experiments demonstrated that overexpression of lnc-AK311120 could restore the phenotype after ALKBH5 knockdown. We observed that AK311120 interacted with the RNA-binding proteins DExH-Box helicase 9 (DHX9) and YTH domain containing 2 (YTHDC2) to form a ternary complex, while mitogen-activated protein kinase kinase 7 (MAP2K7) served as the shared downstream target gene of DHX9 and YTHDC2. Knockdown of AK311120 led to a reduction in the binding affinity between DHX9/YTHDC2 and the target gene MAP2K7. Furthermore, ALKBH5 facilitated the translation of MAP2K7 and activated the downstream JNK signaling pathway through the AK311120-DHX9-YTHDC2 complex, without affecting its messenger RNA level. Collectively, we have investigated the regulatory effect and mechanism of ALKBH5-mediated demethylation of lncRNA in hASC osteogenesis for the first time, offering a promising approach for bone tissue engineering.

人脂肪源性干细胞(hASCs)常用于骨组织再生。N6-甲基腺苷(m6A)修饰已成为一种新的基因表达调控机制,在干细胞成骨分化过程中发挥着关键作用。然而,烷基化修复同源物5(ALKBH5)在hASC成骨过程中的确切作用和机制仍未完全阐明,值得进一步研究。在此,我们采用甲基化RNA免疫沉淀测序、RNA测序和加权基因共表达网络分析等方法,鉴定了hASCs中的一个关键长非编码RNA(lncRNA):lncRNA AK311120。功能实验证明,lnc-AK311120能促进hASCs的成骨分化,而lnc-AK311120的m6A中心位点A发生突变会降低m6A修饰水平。ALKBH5的成骨作用在体外和裸鼠下颌骨缺损模型中都得到了证实。随后的研究发现,敲除ALKBH5会导致lnc-AK311120的m6A修饰水平显著增加,同时lnc-AK311120的表达水平下调。额外的拯救实验表明,过表达lnc-AK311120可以恢复ALKBH5敲除后的表型。我们观察到,AK311120与RNA结合蛋白DExH-Box螺旋酶9(DHX9)和含YTH结构域的2(YTHDC2)相互作用形成三元复合物,而丝裂原活化蛋白激酶激酶7(MAP2K7)是DHX9和YTHDC2的共同下游靶基因。敲除 AK311120 会降低 DHX9/YTHDC2 与靶基因 MAP2K7 的结合亲和力。此外,ALKBH5 促进了 MAP2K7 的翻译,并通过 AK311120-DHX9-YTHDC2 复合物激活了下游的 JNK 信号通路,而不影响其信使 RNA 水平。综上所述,我们首次研究了ALKBH5介导的lncRNA去甲基化在hASC成骨过程中的调控作用和机制,为骨组织工程提供了一种前景广阔的方法。
{"title":"ALKBH5 Regulates Osteogenic Differentiation via the lncRNA/mRNA Complex.","authors":"Y Song, H Gao, Y Pan, Y Gu, W Sun, Y Wang, J Liu","doi":"10.1177/00220345241266775","DOIUrl":"10.1177/00220345241266775","url":null,"abstract":"<p><p>Human adipose-derived stem cells (hASCs) are commonly used in bone tissue regeneration. The N6-methyladenosine (m<sup>6</sup>A) modification has emerged as a novel regulatory mechanism for gene expression, playing a critical role in osteogenic differentiation of stem cells. However, the precise role and mechanism of alkylation repair homolog 5 (ALKBH5) in hASC osteogenesis remain incompletely elucidated and warrant further investigation. Herein, we employed methylated RNA immunoprecipitation sequencing, RNA sequencing, and weighted gene coexpression network analysis to identify a key long noncoding RNA (lncRNA) in hASCs: lncRNA AK311120. Functional experiments demonstrated that lnc-AK311120 promoted the osteogenic differentiation of hASCs, while a mutation at the m<sup>6</sup>A central site A of lnc-AK311120 was found to decrease the level of m<sup>6</sup>A modification. The osteogenic effect of ALKBH5 was confirmed both in vitro and in vivo using a mandibular defect model in nude mice. Subsequent investigations revealed that knockdown of ALKBH5 resulted in a significant increase in the m<sup>6</sup>A modification level of lnc-AK311120, accompanied by a downregulation in the expression level of lnc-AK311120. Additional rescue experiments demonstrated that overexpression of lnc-AK311120 could restore the phenotype after ALKBH5 knockdown. We observed that AK311120 interacted with the RNA-binding proteins DExH-Box helicase 9 (DHX9) and YTH domain containing 2 (YTHDC2) to form a ternary complex, while mitogen-activated protein kinase kinase 7 (MAP2K7) served as the shared downstream target gene of DHX9 and YTHDC2. Knockdown of AK311120 led to a reduction in the binding affinity between DHX9/YTHDC2 and the target gene MAP2K7. Furthermore, ALKBH5 facilitated the translation of MAP2K7 and activated the downstream JNK signaling pathway through the AK311120-DHX9-YTHDC2 complex, without affecting its messenger RNA level. Collectively, we have investigated the regulatory effect and mechanism of ALKBH5-mediated demethylation of lncRNA in hASC osteogenesis for the first time, offering a promising approach for bone tissue engineering.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Letter to the Editor, "Sjögren's Disease Is Not a Clinical Risk Factor for Periodontitis". 致编辑的信,《斯约格伦病不是牙周炎的临床风险因素》。
Pub Date : 2024-10-01 Epub Date: 2024-09-29 DOI: 10.1177/00220345241256583
A Vissink, D J Jager, F Maarse, H Brand
{"title":"Letter to the Editor, \"Sjögren's Disease Is Not a Clinical Risk Factor for Periodontitis\".","authors":"A Vissink, D J Jager, F Maarse, H Brand","doi":"10.1177/00220345241256583","DOIUrl":"10.1177/00220345241256583","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The OHStat Guidelines for Reporting Observational Studies and Clinical Trials in Oral Health Research: Manuscript Checklist. 口腔健康研究观察性研究和临床试验报告 OHStat 指南:手稿核对表。
Pub Date : 2024-10-01 Epub Date: 2024-07-12 DOI: 10.1177/00220345241247028
A M Best, T A Lang, B L Greenberg, J C Gunsolley, E Ioannidou

Adequate and transparent reporting is necessary for critically appraising published research. Yet, ample evidence suggests that the design, conduct, analysis, interpretation, and reporting of oral health research could be greatly improved. Accordingly, the Task Force on Design and Analysis in Oral Health Research-statisticians and trialists from academia and industry-identified the minimum information needed to report and evaluate observational studies and clinical trials in oral health: the OHStat Guidelines. Drafts were circulated to the editors of 85 oral health journals and to Task Force members and sponsors and discussed at a December 2020 workshop attended by 49 researchers. The guidelines were subsequently revised by the Task Force's writing group. The guidelines draw heavily from the Consolidated Standards for Reporting Trials (CONSORT), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), and CONSORT harms guidelines and incorporate the SAMPL guidelines for reporting statistics, the CLIP principles for documenting images, and the GRADE indicating the quality of evidence. The guidelines also recommend reporting estimates in clinically meaningful units using confidence intervals, rather than relying on P values. In addition, OHStat introduces 7 new guidelines that concern the text itself, such as checking the congruence between abstract and text, structuring the discussion, and listing conclusions to make them more specific. OHStat does not replace other reporting guidelines; it incorporates those most relevant to dental research into a single document. Manuscripts using the OHStat guidelines will provide more information specific to oral health research.

充分而透明的报告对于批判性地评估已发表的研究是必要的。然而,大量证据表明,口腔健康研究的设计、实施、分析、解释和报告都可以大大改进。因此,口腔健康研究设计与分析工作组--来自学术界和工业界的统计学家和试验专家--确定了报告和评估口腔健康观察研究和临床试验所需的最低限度信息:OHStat 指南。草案已分发给 85 份口腔健康期刊的编辑以及特别小组成员和赞助商,并在 2020 年 12 月的研讨会上进行了讨论,49 名研究人员参加了此次研讨会。随后,工作组的写作小组对指南进行了修订。该指南在很大程度上借鉴了《试验报告统一标准》(CONSORT)、《加强流行病学观察性研究报告》(STROBE)和《CONSORT 危害指南》,并纳入了报告统计数据的 SAMPL 指南、记录图像的 CLIP 原则以及表示证据质量的 GRADE。该指南还建议使用置信区间以有临床意义的单位报告估计值,而不是依赖 P 值。此外,OHStat 还引入了 7 项与文本本身有关的新指南,如检查摘要与文本之间的一致性、安排讨论的结构、列出结论使其更具体等。OHStat并不取代其他报告指南,而是将与口腔医学研究最相关的指南整合到一份文件中。使用OHStat指南的手稿将提供更多与口腔健康研究相关的信息。
{"title":"The OHStat Guidelines for Reporting Observational Studies and Clinical Trials in Oral Health Research: Manuscript Checklist.","authors":"A M Best, T A Lang, B L Greenberg, J C Gunsolley, E Ioannidou","doi":"10.1177/00220345241247028","DOIUrl":"10.1177/00220345241247028","url":null,"abstract":"<p><p>Adequate and transparent reporting is necessary for critically appraising published research. Yet, ample evidence suggests that the design, conduct, analysis, interpretation, and reporting of oral health research could be greatly improved. Accordingly, the Task Force on Design and Analysis in Oral Health Research-statisticians and trialists from academia and industry-identified the minimum information needed to report and evaluate observational studies and clinical trials in oral health: the OHStat Guidelines. Drafts were circulated to the editors of 85 oral health journals and to Task Force members and sponsors and discussed at a December 2020 workshop attended by 49 researchers. The guidelines were subsequently revised by the Task Force's writing group. The guidelines draw heavily from the Consolidated Standards for Reporting Trials (CONSORT), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), and CONSORT harms guidelines and incorporate the SAMPL guidelines for reporting statistics, the CLIP principles for documenting images, and the GRADE indicating the quality of evidence. The guidelines also recommend reporting estimates in clinically meaningful units using confidence intervals, rather than relying on <i>P</i> values. In addition, OHStat introduces 7 new guidelines that concern the text itself, such as checking the congruence between abstract and text, structuring the discussion, and listing conclusions to make them more specific. OHStat does not replace other reporting guidelines; it incorporates those most relevant to dental research into a single document. Manuscripts using the OHStat guidelines will provide more information specific to oral health research.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Coloring Multilayer Zirconia May Affect Its Optical and Mechanical Properties. 多层氧化锆着色可能会影响其光学和机械性能
Pub Date : 2024-10-01 Epub Date: 2024-10-04 DOI: 10.1177/00220345241271211
S M Čokić, M Li, S Huang, J Vleugels, B Van Meerbeek, F Zhang

The coloring process of monolithic dental zirconia caused considerable debate on the possible effects of different coloring methods. The main objective of this study was to investigate the influence of pigments in 3 multilayer 5-mol% yttria partially stabilized zirconia (5Y-PSZ) disks (Lava Esthetic A2 [Zr-AGG_A2] and Bleach [Zr-AGG_BL], both 3M Oral Care, and Katana STML A2 [Zr-NoAGG], Kuraray Noritake). The influence of pigment addition on the translucency parameter (TP00), fracture toughness, Vickers hardness, biaxial strength, and hydrothermal stability was assessed and correlated with the microstructure and phase composition. The pigment composition and distribution were evaluated by light and fluorescence microscopy, electron probe microanalysis, and nano-scanning electron microscopy. The chemical and phase composition and aging behavior were assessed using X-ray fluorescence and X-ray diffraction, respectively, while the aging sensitivity of the pigments was evaluated using micro-Raman spectroscopy. In contrast to Zr-NoAGG, possessing a typical 5Y-PSZ microstructure, the pigment additions in both Zr-AGG_A2/BL zirconia resulted in large yellow and blue fluorescent Er-, Hf-, and Al-containing agglomerates composed of small grains (0.57 µm and 0.38 µm, respectively, vs. 0.92 µm for the surrounding grains) with lower Y2O3 content. Zr-AGG_A2 had the lowest aging resistance, with transformation degradation occurring exclusively within the pigment agglomerates. All zirconia grades had a high Y2O3 content (4.2%-5.7 mol%) tetragonal ZrO2 phase and a high (42%-55 wt%) cubic ZrO2 phase content. Although no statistical differences were measured for hardness and toughness, Zr-NoAGG had a significantly higher TP00, higher flexural strength, and lower mechanical reliability compared to both Zr-AGG_A2/BL zirconia. The rare-earth oxide-containing zirconia agglomerates that were added as pigments to the multilayered monolithic Zr-AGG_A2/BL zirconia are the cause for their lower optical and mechanical properties and reduced aging resistance.

整体牙用氧化锆的着色工艺引起了关于不同着色方法可能产生的影响的广泛讨论。本研究的主要目的是调查颜料对 3 种多层 5 摩尔%钇部分稳定氧化锆(5Y-PSZ)盘(Lava Esthetic A2 [Zr-AGG_A2] 和 Bleach [Zr-AGG_BL],均为 3M 口腔护理产品;Katana STML A2 [Zr-NoAGG],Kuraray Noritake)的影响。评估了颜料添加对半透明参数(TP00)、断裂韧性、维氏硬度、双轴强度和水热稳定性的影响,并将其与微观结构和相组成联系起来。颜料的组成和分布通过光显微镜、荧光显微镜、电子探针显微分析和纳米扫描电子显微镜进行了评估。分别使用 X 射线荧光和 X 射线衍射评估了颜料的化学成分和相组成以及老化行为,并使用显微拉曼光谱评估了颜料的老化敏感性。与具有典型 5Y-PSZ 显微结构的 Zr-NoAGG 相反,在 Zr-AGG_A2/BL 氧化锆中添加颜料会产生黄色和蓝色荧光的含 Er、Hf 和 Al 的大型团聚体,这些团聚体由 Y2O3 含量较低的小晶粒(分别为 0.57 µm 和 0.38 µm,而周围晶粒为 0.92 µm)组成。Zr-AGG_A2 的耐老化性最低,转化降解完全发生在颜料团聚体内部。所有氧化锆牌号都具有高 Y2O3 含量(4.2%-5.7 mol%)的四方氧化锆相和高含量(42%-55 wt%)的立方氧化锆相。虽然在硬度和韧性方面没有测得统计差异,但与 Zr-AGG_A2/BL 氧化锆相比,Zr-NoAGG 的 TP00 明显更高,抗折强度更高,机械可靠性更低。作为颜料添加到多层单片 Zr-AGG_A2/BL 氧化锆中的含稀土氧化物的氧化锆团聚体是导致其光学和机械性能降低以及耐老化性降低的原因。
{"title":"Coloring Multilayer Zirconia May Affect Its Optical and Mechanical Properties.","authors":"S M Čokić, M Li, S Huang, J Vleugels, B Van Meerbeek, F Zhang","doi":"10.1177/00220345241271211","DOIUrl":"10.1177/00220345241271211","url":null,"abstract":"<p><p>The coloring process of monolithic dental zirconia caused considerable debate on the possible effects of different coloring methods. The main objective of this study was to investigate the influence of pigments in 3 multilayer 5-mol% yttria partially stabilized zirconia (5Y-PSZ) disks (Lava Esthetic A2 [Zr-AGG_A2] and Bleach [Zr-AGG_BL], both 3M Oral Care, and Katana STML A2 [Zr-NoAGG], Kuraray Noritake). The influence of pigment addition on the translucency parameter (TP<sub>00</sub>), fracture toughness, Vickers hardness, biaxial strength, and hydrothermal stability was assessed and correlated with the microstructure and phase composition. The pigment composition and distribution were evaluated by light and fluorescence microscopy, electron probe microanalysis, and nano-scanning electron microscopy. The chemical and phase composition and aging behavior were assessed using X-ray fluorescence and X-ray diffraction, respectively, while the aging sensitivity of the pigments was evaluated using micro-Raman spectroscopy. In contrast to Zr-NoAGG, possessing a typical 5Y-PSZ microstructure, the pigment additions in both Zr-AGG_A2/BL zirconia resulted in large yellow and blue fluorescent Er-, Hf-, and Al-containing agglomerates composed of small grains (0.57 µm and 0.38 µm, respectively, vs. 0.92 µm for the surrounding grains) with lower Y<sub>2</sub>O<sub>3</sub> content. Zr-AGG_A2 had the lowest aging resistance, with transformation degradation occurring exclusively within the pigment agglomerates. All zirconia grades had a high Y<sub>2</sub>O<sub>3</sub> content (4.2%-5.7 mol%) tetragonal ZrO<sub>2</sub> phase and a high (42%-55 wt%) cubic ZrO<sub>2</sub> phase content. Although no statistical differences were measured for hardness and toughness, Zr-NoAGG had a significantly higher TP<sub>00</sub>, higher flexural strength, and lower mechanical reliability compared to both Zr-AGG_A2/BL zirconia. The rare-earth oxide-containing zirconia agglomerates that were added as pigments to the multilayered monolithic Zr-AGG_A2/BL zirconia are the cause for their lower optical and mechanical properties and reduced aging resistance.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acceleration of HDL-Mediated Cholesterol Efflux Alleviates Periodontitis. 加速高密度脂蛋白介导的胆固醇外流可缓解牙周炎。
Pub Date : 2024-10-01 Epub Date: 2024-09-23 DOI: 10.1177/00220345241271075
T-T Tran, G Lee, Y H Huh, K-H Chung, S Y Lee, K H Park, J-H Kim, M-S Kook, J Ryu, O-S Kim, H-P Lim, J-T Koh, J-H Ryu

Periodontitis (PD) is a common inflammatory disease known to be closely associated with metabolic disorders, particularly hyperlipidemia. In the current study, we demonstrated that hypercholesterolemia is a predisposing factor in the development of PD. Logistic regression analysis revealed a strong positive correlation between PD and dyslipidemia. Data from in vivo (PD mouse model subjected to a high cholesterol diet) and in vitro (cholesterol treatment of gingival fibroblasts [GFs]) experiments showed that excess cholesterol influx into GFs potentially contributes to periodontal inflammation and, subsequently, alveolar bone erosion. Additionally, we compared the protective efficacies of cholesterol-lowering drugs with their different modes of action against PD pathogenesis in mice. Among the cholesterol-lowering drugs we tested, fenofibrate exerted the most protective effect against PD pathogenesis due to an increased level of high-density lipoprotein cholesterol, a lipoprotein involved in cholesterol efflux from cells and reverse cholesterol transport. Indeed, cholesterol efflux was suppressed during PD progression by downregulation of the apoA-I binding protein (APOA1BP) expression in inflamed GFs. We also demonstrated that the overexpression of APOA1BP efficiently regulated periodontal inflammation and the subsequent alveolar bone loss by inducing cholesterol efflux. Our collective findings highlight the potential utility of currently available cholesterol-lowering medications for the mitigation of PD pathogenesis. By targeting the acceleration of high-density lipoprotein-mediated cellular cholesterol efflux, a new therapeutic approach for PD may become possible.

牙周炎(PD)是一种常见的炎症性疾病,已知与代谢紊乱,尤其是高脂血症密切相关。在本研究中,我们证实高胆固醇血症是牙周炎发病的一个易感因素。逻辑回归分析表明,帕金森病与血脂异常之间存在很强的正相关性。体内(高胆固醇饮食下的 PD 小鼠模型)和体外(胆固醇处理牙龈成纤维细胞 [GFs])实验的数据显示,过量胆固醇流入牙龈成纤维细胞可能会导致牙周炎症,进而造成牙槽骨侵蚀。此外,我们还比较了不同作用模式的降胆固醇药物对小鼠肺结核发病机制的保护作用。在我们测试的降胆固醇药物中,非诺贝特对帕金森病发病机制的保护作用最强,因为它能提高高密度脂蛋白胆固醇的水平,而高密度脂蛋白胆固醇参与细胞中胆固醇的外流和胆固醇的逆向转运。事实上,在帕金森氏症进展过程中,胆固醇外流会因载脂蛋白A-I结合蛋白(APOA1BP)在发炎的GFs中表达下调而受到抑制。我们还证明,过量表达 APOA1BP 可通过诱导胆固醇外流有效调节牙周炎症和随后的牙槽骨流失。我们的研究结果凸显了目前可用的降胆固醇药物在缓解牙周病发病机制方面的潜在作用。通过以加速高密度脂蛋白介导的细胞胆固醇外流为目标,一种新的治疗脑退化症的方法可能成为可能。
{"title":"Acceleration of HDL-Mediated Cholesterol Efflux Alleviates Periodontitis.","authors":"T-T Tran, G Lee, Y H Huh, K-H Chung, S Y Lee, K H Park, J-H Kim, M-S Kook, J Ryu, O-S Kim, H-P Lim, J-T Koh, J-H Ryu","doi":"10.1177/00220345241271075","DOIUrl":"10.1177/00220345241271075","url":null,"abstract":"<p><p>Periodontitis (PD) is a common inflammatory disease known to be closely associated with metabolic disorders, particularly hyperlipidemia. In the current study, we demonstrated that hypercholesterolemia is a predisposing factor in the development of PD. Logistic regression analysis revealed a strong positive correlation between PD and dyslipidemia. Data from in vivo (PD mouse model subjected to a high cholesterol diet) and in vitro (cholesterol treatment of gingival fibroblasts [GFs]) experiments showed that excess cholesterol influx into GFs potentially contributes to periodontal inflammation and, subsequently, alveolar bone erosion. Additionally, we compared the protective efficacies of cholesterol-lowering drugs with their different modes of action against PD pathogenesis in mice. Among the cholesterol-lowering drugs we tested, fenofibrate exerted the most protective effect against PD pathogenesis due to an increased level of high-density lipoprotein cholesterol, a lipoprotein involved in cholesterol efflux from cells and reverse cholesterol transport. Indeed, cholesterol efflux was suppressed during PD progression by downregulation of the apoA-I binding protein (APOA1BP) expression in inflamed GFs. We also demonstrated that the overexpression of APOA1BP efficiently regulated periodontal inflammation and the subsequent alveolar bone loss by inducing cholesterol efflux. Our collective findings highlight the potential utility of currently available cholesterol-lowering medications for the mitigation of PD pathogenesis. By targeting the acceleration of high-density lipoprotein-mediated cellular cholesterol efflux, a new therapeutic approach for PD may become possible.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Trustworthy Artificial Intelligence in Dentistry: Learnings from the EU AI Act. 牙科领域值得信赖的人工智能:从欧盟人工智能法案中汲取经验。
Pub Date : 2024-10-01 Epub Date: 2024-09-23 DOI: 10.1177/00220345241271160
M Ducret, E Wahal, D Gruson, S Amrani, R Richert, M Mouncif-Moungache, F Schwendicke

Artificial intelligence systems (AISs) gain relevance in dentistry, encompassing diagnostics, treatment planning, patient management, and therapy. However, questions about the generalizability, fairness, and transparency of these systems remain. Regulatory and governance bodies worldwide are aiming to address these questions using various frameworks. On March 13, 2024, members of the European Parliament approved the Artificial Intelligence Act (AIA), which emphasizes trustworthiness and human-centeredness as relevant aspects to regulate AISs beyond safety and efficacy. This review presents the AIA and similar regulatory and governance efforts in other jurisdictions and lays out that regulations such as the AIA are part of a complex ecosystem of interdependent and interwoven legal requirements and standards. Current efforts to regulate dental AISs require active input from the dental community, with participation of dental research, education, providers, and patients being relevant to shape the future of dental AISs.

人工智能系统(AIS)在牙科领域的应用越来越广泛,包括诊断、治疗计划、病人管理和治疗。然而,关于这些系统的通用性、公平性和透明度的问题依然存在。世界各地的监管和治理机构正致力于利用各种框架来解决这些问题。2024 年 3 月 13 日,欧洲议会成员批准了《人工智能法案》(AIA),该法案强调可信度和以人为本是监管人工智能系统除安全性和有效性之外的相关方面。本综述介绍了《人工智能法》以及其他司法管辖区的类似监管和治理工作,并指出像《人工智能法》这样的法规是由相互依存、相互交织的法律要求和标准组成的复杂生态系统的一部分。目前监管牙科 AIS 的努力需要牙科界的积极投入,牙科研究、教育、提供者和患者的参与对于塑造牙科 AIS 的未来至关重要。
{"title":"Trustworthy Artificial Intelligence in Dentistry: Learnings from the EU AI Act.","authors":"M Ducret, E Wahal, D Gruson, S Amrani, R Richert, M Mouncif-Moungache, F Schwendicke","doi":"10.1177/00220345241271160","DOIUrl":"10.1177/00220345241271160","url":null,"abstract":"<p><p>Artificial intelligence systems (AISs) gain relevance in dentistry, encompassing diagnostics, treatment planning, patient management, and therapy. However, questions about the generalizability, fairness, and transparency of these systems remain. Regulatory and governance bodies worldwide are aiming to address these questions using various frameworks. On March 13, 2024, members of the European Parliament approved the Artificial Intelligence Act (AIA), which emphasizes trustworthiness and human-centeredness as relevant aspects to regulate AISs beyond safety and efficacy. This review presents the AIA and similar regulatory and governance efforts in other jurisdictions and lays out that regulations such as the AIA are part of a complex ecosystem of interdependent and interwoven legal requirements and standards. Current efforts to regulate dental AISs require active input from the dental community, with participation of dental research, education, providers, and patients being relevant to shape the future of dental AISs.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142304941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Big Data in Epidemiology: Brave New World? 流行病学中的大数据:勇敢的新世界?
Pub Date : 2024-10-01 Epub Date: 2024-10-02 DOI: 10.1177/00220345241272034
R A Jordan, R K Celeste, E Bernabe, F Schwendicke

Epidemiology is experiencing a significant shift toward the utilization of big data for health monitoring and decision-making. This article discusses the recent example of the World Health Organization (WHO) global oral health status report and regional summaries, which faced criticisms due to its reliance on big data from the Global Burden of Disease (GBD) study. We address the arguments for and against the use of big data in epidemiology and provide an assessment of the value and limitations of big data epidemiology. Moreover, we provide recommendations as to how the oral health community should reconcile traditional epidemiologic approaches with big data and advanced data analytics. This Perspective article highlights the challenges of the current epidemiologic landscape, the potential of big data, and the need for a balanced approach to data utilization in epidemiology.

流行病学正在经历向利用大数据进行健康监测和决策的重大转变。本文讨论了世界卫生组织(WHO)最近发布的全球口腔健康状况报告和区域摘要,该报告由于依赖全球疾病负担(GBD)研究的大数据而受到批评。我们讨论了支持和反对在流行病学中使用大数据的论点,并对大数据流行病学的价值和局限性进行了评估。此外,我们还就口腔健康界应如何协调传统流行病学方法与大数据和高级数据分析提出了建议。这篇 "视角 "文章强调了当前流行病学面临的挑战、大数据的潜力以及在流行病学中平衡利用数据的必要性。
{"title":"Big Data in Epidemiology: Brave New World?","authors":"R A Jordan, R K Celeste, E Bernabe, F Schwendicke","doi":"10.1177/00220345241272034","DOIUrl":"10.1177/00220345241272034","url":null,"abstract":"<p><p>Epidemiology is experiencing a significant shift toward the utilization of big data for health monitoring and decision-making. This article discusses the recent example of the World Health Organization (WHO) global oral health status report and regional summaries, which faced criticisms due to its reliance on big data from the Global Burden of Disease (GBD) study. We address the arguments for and against the use of big data in epidemiology and provide an assessment of the value and limitations of big data epidemiology. Moreover, we provide recommendations as to how the oral health community should reconcile traditional epidemiologic approaches with big data and advanced data analytics. This Perspective article highlights the challenges of the current epidemiologic landscape, the potential of big data, and the need for a balanced approach to data utilization in epidemiology.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Six1 Regulates Mouse Incisor Development by Promoting Dlx1/2/5 Expression. Six1 通过促进 Dlx1/2/5 的表达调控小鼠门齿的发育
Pub Date : 2024-09-01 Epub Date: 2024-08-05 DOI: 10.1177/00220345241256286
S Y Luo, S Wang, Z X Liu, Q Bian, X D Wang

Tooth development is a complex process orchestrated by intricate gene regulatory networks, involving both odontogenic epithelium and ectomesenchyme. Six1, a pivotal transcription factor (TF), is involved in the development of the lower incisor. However, its precise role during incisor development and the molecular mechanisms underpinning its regulatory functions remain poorly understood. This study employs Six1 deletion mouse models to elucidate the critical regulatory role of Six1 in governing dental mesenchyme development. By performing single-cell RNA sequencing, we constructed a comprehensive transcriptome atlas of tooth germ development from the bud to bell stage. Our analyses suggest that the dental follicle and the dental papilla (DP) are differentiated from dental ectomesenchyme (DEM) and identify the key TFs underlying these distinct states. Notably, we show that Dlx1, Dlx2, and Dlx5 (Dlx1/2/5) may function as the key TFs that promote the formation of DP. We further show that the deletion of Six1 perturbs dental mesenchyme development by impeding the transitions from DEM to DP states. Importantly, SIX1 directly binds to the promoters of Dlx1/2/5 to promote their co-expression, which subsequently leads to widespread epigenetic and transcriptional remodeling. In summary, our findings unveil Six1's indispensable role in incisor development, offering key insights into TF-driven regulatory networks that govern dental mesenchyme cell fate transitions during tooth development.

牙齿发育是一个复杂的过程,由错综复杂的基因调控网络协调,涉及牙源性上皮和外胚层。Six1是一种关键的转录因子(TF),参与了下切牙的发育。然而,人们对它在门牙发育过程中的确切作用及其调控功能的分子机制仍然知之甚少。本研究利用Six1缺失小鼠模型来阐明Six1在牙齿间质发育过程中的关键调控作用。通过进行单细胞 RNA 测序,我们构建了一个全面的转录组图谱,该图谱涵盖了从萌芽到钟期的牙胚发育过程。我们的分析表明,牙泡和牙乳头(DP)是从牙外胚层(DEM)分化出来的,并确定了这些不同状态下的关键 TFs。值得注意的是,我们发现 Dlx1、Dlx2 和 Dlx5(Dlx1/2/5)可能是促进 DP 形成的关键 TF。我们进一步发现,Six1的缺失会阻碍牙间质从DEM向DP状态的转变,从而扰乱牙间质的发育。重要的是,SIX1直接与Dlx1/2/5的启动子结合,促进它们的共同表达,随后导致广泛的表观遗传和转录重塑。总之,我们的研究结果揭示了SIX1在门牙发育过程中不可或缺的作用,为了解牙齿发育过程中牙间质细胞命运转换的TF驱动调控网络提供了重要信息。
{"title":"<i>Six1</i> Regulates Mouse Incisor Development by Promoting <i>Dlx1/2/5</i> Expression.","authors":"S Y Luo, S Wang, Z X Liu, Q Bian, X D Wang","doi":"10.1177/00220345241256286","DOIUrl":"10.1177/00220345241256286","url":null,"abstract":"<p><p>Tooth development is a complex process orchestrated by intricate gene regulatory networks, involving both odontogenic epithelium and ectomesenchyme. <i>Six1</i>, a pivotal transcription factor (TF), is involved in the development of the lower incisor. However, its precise role during incisor development and the molecular mechanisms underpinning its regulatory functions remain poorly understood. This study employs <i>Six1</i> deletion mouse models to elucidate the critical regulatory role of <i>Six1</i> in governing dental mesenchyme development. By performing single-cell RNA sequencing, we constructed a comprehensive transcriptome atlas of tooth germ development from the bud to bell stage. Our analyses suggest that the dental follicle and the dental papilla (DP) are differentiated from dental ectomesenchyme (DEM) and identify the key TFs underlying these distinct states. Notably, we show that <i>Dlx1</i>, <i>Dlx2</i>, and <i>Dlx5</i> (<i>Dlx1</i>/<i>2</i>/<i>5</i>) may function as the key TFs that promote the formation of DP. We further show that the deletion of <i>Six1</i> perturbs dental mesenchyme development by impeding the transitions from DEM to DP states. Importantly, SIX1 directly binds to the promoters of <i>Dlx1</i>/<i>2</i>/<i>5</i> to promote their co-expression, which subsequently leads to widespread epigenetic and transcriptional remodeling. In summary, our findings unveil <i>Six1</i>'s indispensable role in incisor development, offering key insights into TF-driven regulatory networks that govern dental mesenchyme cell fate transitions during tooth development.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of dental research
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1