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Cost-Effectiveness of AI-Assisted Detection of Apical Periodontitis on Panoramic Radiographs. 全景x线片上人工智能辅助检测根尖牙周炎的成本-效果。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-03-13 DOI: 10.1111/iej.70142
Leander Benz, Utku Pul, Tobias Brock, Falk Schwendicke, Elias Walter

Background: Artificial intelligence (AI) is transforming medical imaging, yet its economic impact in dentistry remains largely unexplored.

Aim: This study evaluated the cost-effectiveness of AI-assisted detection of apical periodontitis on panoramic radiographs, including downstream clinical decision-making.

Material and methods: Using data from a randomised study on AI-assisted detection of apical lesions, a decision-analytic model was established to analyse costs and effectiveness from a German mixed-payer perspective.

Results: AI support reduced average costs per case and increased treatment effectiveness, outperforming unaided examiner performance. These gains were primarily driven by improved specificity, reducing false-positive detection. However, effects varied by examiner experience; junior clinicians achieved the greatest cost savings and effectiveness gains, whereas senior examiners showed reduced sensitivity and slightly lower effectiveness at similar costs.

Conclusion: AI-assisted diagnostics offer significant potential to improve cost-effectiveness by reducing overtreatment, with benefits being most pronounced among less experienced practitioners. Adapting AI systems to individual examiners or experience levels might further enhance clinical and economic impact.

背景:人工智能(AI)正在改变医学成像,但其对牙科的经济影响在很大程度上仍未被探索。目的:本研究评估在全景x线片上人工智能辅助检测根尖牙周炎的成本效益,包括下游临床决策。材料和方法:利用人工智能辅助检测根尖病变的随机研究数据,建立决策分析模型,从德国混合付款人的角度分析成本和效果。结果:人工智能支持降低了每个病例的平均成本,提高了治疗效果,优于独立审查员的表现。这些成果主要是由于特异性的提高,减少了假阳性检测。然而,效果因考官经验而异;初级临床医生获得了最大的成本节约和有效性收益,而高级检查人员在相同的成本下显示出降低的敏感性和略低的有效性。结论:人工智能辅助诊断通过减少过度治疗,为提高成本效益提供了巨大的潜力,在经验不足的从业者中获益最为明显。使人工智能系统适应个人审查员或经验水平可能会进一步增强临床和经济影响。
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引用次数: 0
A Comparison of Endodontic Microbiomes Associated With Symptomatic and Asymptomatic Apical Periodontitis by Next-Generation Sequencing. 用新一代测序方法比较与症状性和无症状性牙周炎相关的牙髓微生物组。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-03-13 DOI: 10.1111/iej.70140
David Donnermeyer, Edgar Schäfer, Daniel Hagenfeld, Benjamin Ehmke, Karola Prior, Dag Harmsen, Madgalena Ibing, Sebastian Bürklein, Thomas Gerhard Wolf, Johannes Matern

Aim: This cross-sectional study aimed to compare the endodontic microbiome assessed from root canals of teeth associated with either symptomatic or asymptomatic apical periodontitis and analysed by 16S rDNA gene sequencing.

Methodology: 60 teeth presenting clinical and radiographic signs of symptomatic or asymptomatic apical periodontitis (n = 30) were included in this cross-sectional study after participants had given their written informed consent. After isolation with rubber dam, disinfection and access cavity preparation, glide paths were prepared using C-Pilot Files and K-Files under electronic root canal length control. Microbial samples were collected from a total of 120 root canals (symptomatic apical periodontitis, SAP: n = 62, asymptomatic apical periodontitis, AAP: n = 58) each with a sterile file (size 20/0.06) in a single length technique. Only one specimen per tooth was included in the analysis; in multi-rooted teeth, the specimen with highest sequencing depth. After DNA extraction, the hypervariable region V4 of the bacterial 16 S rRNA gene was amplified and sequenced (Illumina MiSeq). Taxonomy was assigned based on the expanded Human Oral Microbiome Database (eHOMD). Statistical analysis of diversity parameters comprised Mann-Whitney U tests and PERMANOVA. Compositional differences were evaluated by differential abundance analyses using DESeq2, LinDA, and ANCOM-BC2 methods.

Results: No differences were observed in richness and diversity (Shannon diversity index) on the genus or ASV level (p > 0.05). According to PERMANOVA, SAP and AAP microbiomes did not differ significantly both on genus and ASV levels (p > 0.05). Among highly abundant genera, Fusobacterium was indicated to be more abundant in SAP samples whereas Actinomyces was more abundant in AAP samples.

Conclusions: The expression of clinical symptoms in apical periodontitis does not appear to be determined by specific microorganisms but may instead reflect shifts of the relative abundance of the microbial community.

目的:本横断面研究旨在比较从有症状或无症状的根尖牙炎患者的牙根管中评估的牙髓微生物组,并通过16S rDNA基因测序进行分析。方法:在参与者书面知情同意后,60颗牙齿(n = 30)表现出有症状或无症状的根尖牙周炎的临床和放射学迹象,被纳入这项横断面研究。经橡胶坝隔离、消毒、预备通道腔后,在电子根管长度控制下,用C-Pilot锉和k -锉制备滑动路径。采用单长度技术,用无菌锉(尺寸为20/0.06)从120个根管(症状性根尖牙炎,SAP: n = 62,无症状性根尖牙炎,AAP: n = 58)中采集微生物样本。每颗牙齿只有一个标本被纳入分析;在多根牙齿中,排序深度最高的标本。提取DNA后,扩增细菌16s rRNA基因高变区V4并测序(Illumina MiSeq)。根据扩展的人类口腔微生物组数据库(eHOMD)进行分类。多样性参数的统计分析采用Mann-Whitney U检验和PERMANOVA检验。采用DESeq2、LinDA和ANCOM-BC2方法进行差异丰度分析,评估成分差异。结果:在属和ASV水平上,丰富度和多样性(Shannon多样性指数)均无显著差异(p < 0.05)。根据PERMANOVA的研究,SAP和AAP微生物组在属和ASV水平上无显著差异(p < 0.05)。在丰度较高的菌属中,SAP样品中梭杆菌含量较高,而AAP样品中放线菌含量较高。结论:根尖牙周炎的临床症状表现似乎不是由特定的微生物决定的,而是反映了微生物群落相对丰度的变化。
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引用次数: 0
The Efficacy of Intracanal Medicaments Within the Regenerative Endodontic Procedures on Permanent Necrotic Immature Teeth: Systematic Review and Naïve Indirect-Comparison Meta-Analysis. 再生牙根管治疗永久性坏死未成熟牙的疗效:系统回顾和Naïve间接比较meta分析。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-03-12 DOI: 10.1111/iej.70135
Mario Alovisi, Paolo G Arduino, Stefano Petti

Objectives: The objectives of this study were to estimate and compare the 1-year clinical success rates of triple antibiotic paste (TAP), double antibiotic paste (DAP), calcium hydroxide (CH) within regenerative endodontic procedures (REPs) on permanent necrotic immature teeth.

Materials and methods: Trials investigating REP success were searched through MEDLINE, Scopus, Embase, Web of Science, GOOGLE Scholar (last update December 2025). Primary study quality was evaluated through the revised Cochrane Risk of Bias tool for Randomised Trials (RoB2). Pooled success rates with 95% confidence intervals (95% CIs) were assessed. Heterogeneity was investigated with the Cochran's Q and quantified with I2: The random-effects model was preferred to the fixed-effect model for I2 > 50%. Sensitivity (study quality, publication bias, study inclusion) and subgroup (scaffold type, world Region) analyses were made. The differences in pooled success rates between protocols were assessed and were evaluated using an equivalence range of -2.5%/+2.5%. The GRADE system was employed to evaluate the Quality of Evidence of the pooled success rates.

Results: Twenty-four studies of average quality were included involving 544, 64, 183 patients, for TAP, DAP, CH, respectively. The pooled success rates (tooth survival after 1 year with periapical healing, absence of signs and symptoms of pathology) were TAP 96.7% (95% CI, 94.8%-98.0%), DAP 84.2% (95% CI, 73.2%-92.0%), CH 97.4% (95% CI, 93.9%-99.1%). The pooled differences in success rates were TAP-DAP 12.5% (95% CI, 2.8%-22.1%, TAP superiority demonstrated), TAP-CH -0.7% (95% CI, -0.9%-2.5%, TAP/CH equivalence demonstrated), CH-DAP 13.2% (95% CI, 3.3%-23.0%, CH superiority demonstrated). Secondary analyses corroborated these results, although the overall statistical test power was low due to small sample sizes. The GRADE quality of evidence was high for TAP and CH, and low for DAP, due to substantial imprecision attributed to the small number of studies with small sample sizes.

Conclusions: The lack of direct comparisons between protocols and of a common comparator did not allow for more robust analyses. Nevertheless, the use of TAP and CH as intracanal medicament within REPs resulted equivalent in eradicating the infection and promoting periapical healing in permanent necrotic immature teeth at 1-year follow up, and these protocols resulted superior over DAP.

Registration: PROSPERO registration number: CRD42023484189.

目的:本研究的目的是评估和比较三抗生素糊剂(TAP)、双抗生素糊剂(DAP)、氢氧化钙(CH)在再生牙髓治疗(rep)中治疗永久性坏死未成熟牙齿的1年临床成功率。材料和方法:通过MEDLINE, Scopus, Embase, Web of Science,谷歌Scholar(最近更新于2025年12月)检索调查REP成功的试验。通过修订后的Cochrane随机试验偏倚风险工具(RoB2)评估主要研究质量。以95%置信区间(95% ci)评估合并成功率。采用Cochran’s Q进行异质性研究,并采用I2进行量化:当I2达到50%时,随机效应模型优于固定效应模型。进行敏感性(研究质量、发表偏倚、研究纳入)和亚组(支架类型、世界地区)分析。采用-2.5%/+2.5%的等效范围评估不同方案的总成功率差异。GRADE系统用于评估合并成功率的证据质量。结果:平均质量纳入24项研究,分别涉及544例、64例、183例,分别为TAP、DAP、CH。总成功率(1年后根尖周愈合,无病理体征和症状)为TAP 96.7% (95% CI, 94.8%-98.0%), DAP 84.2% (95% CI, 73.2%-92.0%), CH 97.4% (95% CI, 93.9%-99.1%)。总成功率差异为TAP- dap 12.5% (95% CI, 2.8%-22.1%,证明TAP具有优势),TAP-CH -0.7% (95% CI, -0.9%-2.5%,证明TAP/CH等效),CH- dap 13.2% (95% CI, 3.3%-23.0%,证明CH具有优势)。二次分析证实了这些结果,尽管由于样本量小,总体统计检验能力较低。TAP和CH证据的GRADE质量较高,DAP证据的GRADE质量较低,这是由于研究数量少、样本量小导致的大量不精确。结论:缺乏方案之间的直接比较和共同比较物不能进行更有力的分析。然而,在REPs中使用TAP和CH作为管内药物,在1年随访中根除永久性坏死未成熟牙齿的感染和促进根尖周愈合的效果相同,这些方案优于DAP。注册:普洛斯彼罗注册号:CRD42023484189。
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引用次数: 0
Microenvironmental Challenges in Regenerative Endodontic Procedures: Disinfection, Tissue Engineering and Future Directions. 再生牙髓治疗中的微环境挑战:消毒、组织工程和未来方向。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-03-09 DOI: 10.1111/iej.70139
Sahng G Kim, Prasanna Neelakantan, Maobin Yang

True regeneration of the pulp-dentine complex is the ultimate goal of regenerative endodontic procedures (REPs). Despite favourable clinical outcomes, such as resolution of apical periodontitis, continued root elongation and apical closure, histological evidence suggests that most clinical cases result in tissue repair rather than true regeneration. This discrepancy arises from the intricate requirements for optimising the microenvironment, which encompasses two essential stages: disinfection and regeneration. These two stages are not necessarily sequential; they can overlap and be highly interconnected, influencing each other. Current REPs protocols have limitations in both disinfection and regeneration. Endodontic biofilms exhibit a notable tolerance to disinfectants and have the capability of recovery, which negatively affects the odontogenic potential of stem cells. Additionally, immune cells, particularly M1 and M2 macrophages, interact with stem cells and affect their regenerative capacity. Standard irrigants and intracanal medicaments often fail to eliminate biofilms, compromising stem cell viability and differentiation potential. On the regeneration side, age-related decline in stem cell function reduces cell survival and differentiation capacity, while insufficient delivery and lack of control over signalling molecules limit odontogenesis, angiogenesis, and neurogenesis. Commonly used scaffolds for REPs lack the structural, biochemical and biological precision required to guide regeneration of well-organised tissue. Furthermore, a microenvironment characterised by hypoxia, restricted nutrients and limited neurovascular ingrowth further constrains regenerative outcomes. This review will focus on the limitations of the current regenerative microenvironment in REPs and discuss emerging strategies aimed at integrating infection control with tissue engineering design. It also highlights the need for novel antimicrobial approaches and advanced tissue engineering strategies in REPs. Multifunctional biomaterials, such as chitosan nanoparticles, antimicrobial peptides and hierarchically structured scaffolds, may ultimately facilitate true biological regeneration of the pulp-dentine complex.

牙髓-牙本质复合体的真正再生是再生牙髓治疗的最终目标。尽管有良好的临床结果,如根尖牙周炎的消退,持续的根伸长和根尖闭合,组织学证据表明,大多数临床病例导致组织修复而不是真正的再生。这种差异源于优化微环境的复杂要求,其中包括两个基本阶段:消毒和再生。这两个阶段不一定是连续的;它们可以重叠,高度相互联系,相互影响。目前的REPs方案在消毒和再生方面都有局限性。牙髓生物膜对消毒剂表现出显著的耐受性和恢复能力,这对干细胞的成牙潜能产生了负面影响。此外,免疫细胞,特别是M1和M2巨噬细胞,与干细胞相互作用并影响其再生能力。标准冲洗剂和肛管内药物往往不能消除生物膜,损害干细胞的活力和分化潜力。在再生方面,与年龄相关的干细胞功能下降降低了细胞存活和分化能力,而传递不足和缺乏对信号分子的控制限制了牙生成、血管生成和神经生成。常用的REPs支架缺乏引导组织良好的组织再生所需的结构、生化和生物学精度。此外,以缺氧、营养受限和神经血管生长受限为特征的微环境进一步限制了再生结果。这篇综述将重点讨论当前再生微环境在REPs中的局限性,并讨论旨在将感染控制与组织工程设计相结合的新兴策略。这也强调了在rep中需要新的抗菌方法和先进的组织工程策略。多功能生物材料,如壳聚糖纳米颗粒,抗菌肽和分层结构支架,可能最终促进牙髓-牙本质复合体的真正生物再生。
{"title":"Microenvironmental Challenges in Regenerative Endodontic Procedures: Disinfection, Tissue Engineering and Future Directions.","authors":"Sahng G Kim, Prasanna Neelakantan, Maobin Yang","doi":"10.1111/iej.70139","DOIUrl":"https://doi.org/10.1111/iej.70139","url":null,"abstract":"<p><p>True regeneration of the pulp-dentine complex is the ultimate goal of regenerative endodontic procedures (REPs). Despite favourable clinical outcomes, such as resolution of apical periodontitis, continued root elongation and apical closure, histological evidence suggests that most clinical cases result in tissue repair rather than true regeneration. This discrepancy arises from the intricate requirements for optimising the microenvironment, which encompasses two essential stages: disinfection and regeneration. These two stages are not necessarily sequential; they can overlap and be highly interconnected, influencing each other. Current REPs protocols have limitations in both disinfection and regeneration. Endodontic biofilms exhibit a notable tolerance to disinfectants and have the capability of recovery, which negatively affects the odontogenic potential of stem cells. Additionally, immune cells, particularly M1 and M2 macrophages, interact with stem cells and affect their regenerative capacity. Standard irrigants and intracanal medicaments often fail to eliminate biofilms, compromising stem cell viability and differentiation potential. On the regeneration side, age-related decline in stem cell function reduces cell survival and differentiation capacity, while insufficient delivery and lack of control over signalling molecules limit odontogenesis, angiogenesis, and neurogenesis. Commonly used scaffolds for REPs lack the structural, biochemical and biological precision required to guide regeneration of well-organised tissue. Furthermore, a microenvironment characterised by hypoxia, restricted nutrients and limited neurovascular ingrowth further constrains regenerative outcomes. This review will focus on the limitations of the current regenerative microenvironment in REPs and discuss emerging strategies aimed at integrating infection control with tissue engineering design. It also highlights the need for novel antimicrobial approaches and advanced tissue engineering strategies in REPs. Multifunctional biomaterials, such as chitosan nanoparticles, antimicrobial peptides and hierarchically structured scaffolds, may ultimately facilitate true biological regeneration of the pulp-dentine complex.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389911","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}
引用次数: 0
Factors Associated With the Citation Impact of Evidence Synthesis Reviews in Endodontics: A Bibliometric Analysis. 与牙髓学证据综合评价的引用影响相关的因素:文献计量学分析。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-03-09 DOI: 10.1111/iej.70133
Rafaella Rodrigues da Gama, Lucas Peixoto de Araújo, Melissa Feres Damian, Wellington Luiz de Oliveira da Rosa

Background: Systematic reviews are essential for evidence-based decision-making in endodontics, and their number has grown substantially in recent years. However, little is known about the publication patterns, methodological features and citation impact of these studies.

Objectives: To perform a bibliometric analysis of evidence synthesis reviews (including systematic, scoping, bibliometric and umbrella reviews) in endodontics published between 2018 and 2023, and to evaluate the associations between citation impact and demographic, article-related, author-related and journal-related variables.

Methods: This bibliometric analysis was reported in accordance with the PRISMA 2020 guidelines and was registered in the Open Science Framework (https://osf.io/jf9et/). A comprehensive search was conducted in five databases (PubMed, Embase, Web of Science, Scopus and Cochrane Library). Inclusion criteria encompassed systematic, scoping, umbrella and bibliometric reviews in endodontics. Citation data were extracted from Scopus and Google Scholar. Data analysis included descriptive statistics and negative binomial regression to assess associations with citation counts.

Results: Of 9683 records identified, 511 endodontic reviews met the inclusion criteria. Most were published in 2022-2023, predominantly by authors from Asia, Europe and the Americas. Brazil had the highest publication volume, while the USA led in citations. PRISMA adherence was high (90%), but funding and conflict of interest disclosures were infrequent. Citation impact was positively associated with earlier publication year, the last author's h-index, the number of included studies and journal CiteScore. Methodological factors such as protocol registration and article-related variables like open access were not significantly associated with citations after adjustment.

Conclusion: The citation impact of endodontic evidence synthesis reviews is primarily influenced by temporal factors, author academic standing and journal prestige rather than methodological rigour alone. These findings reveal a disconnect between indicators of research quality and citation performance and highlight the necessity of promoting transparency as a scientific value rather than as a surrogate for visibility.

Trial registration: This study was registered in the Open Science Framework (https://osf.io/jf9et/).

背景:系统评价对牙髓学的循证决策至关重要,近年来系统评价的数量大幅增长。然而,人们对这些研究的发表模式、方法特点和被引影响知之甚少。目的:对2018年至2023年间发表的牙髓学证据综合评价(包括系统评价、范围评价、文献计量学和总括性评价)进行文献计量分析,并评估引文影响与人口统计学、文章相关、作者相关和期刊相关变量之间的关联。方法:文献计量学分析按照PRISMA 2020指南报告,并在开放科学框架(https://osf.io/jf9et/)注册。在5个数据库(PubMed, Embase, Web of Science, Scopus和Cochrane Library)中进行了全面的检索。纳入标准包括牙髓学的系统、范围、概括性和文献计量学综述。引文数据提取自Scopus和谷歌Scholar。数据分析包括描述性统计和负二项回归来评估与引用计数的关联。结果:在9683条记录中,511条根管评价符合纳入标准。大部分出版于2022-2023年,作者主要来自亚洲、欧洲和美洲。巴西的论文发表量最高,而美国的论文引用量最高。PRISMA的依从性很高(90%),但资金和利益冲突披露很少。被引影响与论文发表年份、最后一位作者的h指数、被收录研究数量和期刊CiteScore呈正相关。方法学因素,如协议注册和文章相关变量,如开放获取,与调整后的引用没有显著相关。结论:牙髓证据综合综述的引用影响主要受时间因素、作者学术地位和期刊声望的影响,而不仅仅是方法的严谨性。这些发现揭示了研究质量指标与引用绩效之间的脱节,并强调了将透明度作为科学价值而不是可见性的替代品来促进的必要性。试验注册:本研究已在开放科学框架(https://osf.io/jf9et/)注册。
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引用次数: 0
Sensory Nerves Regulate Odontoblast Differentiation via the SPP1/ITGA4 Axis During Tooth Root Development. 牙根发育过程中,感觉神经通过SPP1/ITGA4轴调控成牙细胞分化。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-03-08 DOI: 10.1111/iej.70129
Huanyan Zuo, Jiahao Han, Jiawei Wu, Meng Liu, Yunjie Shuai, Diduo Tian, Fei Pei

Aim: The stem/progenitor cell is crucial for organogenesis. Sensory nerves, as key components of the stem cell niche, secrete various factors to modulate stem/progenitor cell fate decision. Here, we utilised tooth root development as a model to explore the role of sensory nerves in this regulatory process and to elucidate the underlying mechanism.

Methodology: Spatiotemporal dynamics of nerve innervation were characterised during tooth root development. We treated mouse dental papilla cells (mDPCs) with trigeminal ganglion-conditioned medium (TG-CM) and employed a subrenal co-culture of TG-tooth germ to evaluate sensory nerve function in odontoblastic differentiation and tooth root formation. A subrenal co-culture of TG-tooth germ was employed to detect sensory nerve function in tooth root formation. Integrated analysis of scRNA-seq from the TG and molar at post-natal day 3.5 (PN3.5) and PN30 identified potential nerve-derived factors, which were further assessed through subrenal transplantation with recombinant protein-loaded or neutralising antibody-loaded beads. CellChat was used to analyse cell-cell communication between TGs and molars. Co-immunoprecipitation (Co-IP) and proximity ligation assays (PLA) were used to confirm the interaction between secreted phosphoprotein 1 (SPP1) and integrin alpha 4 (ITGA4). The siRNA-mediated Itga4 knockdown assessed its role in odontoblastic differentiation.

Results: Sensory nerve fibres localized to the apical papilla and follicle at PN3.5 and extended toward the crown. TG-CM and subrenal co-culture of TG-tooth germ enhanced odontoblast differentiation and root elongation, demonstrating the indispensable role of sensory nerves for proper root development. Integrated scRNA-seq analysis of TG and molar at PN3.5 and PN30 uncovered various sensory nerve-derived factors, including SPP1, calcitonin gene-related polypeptide (CGRP) and kit ligand (KITL), whose function in tooth root development was validated in vivo. Furthermore, CellChat analysis revealed SPP1-ITGA4 as a critical ligand-receptor interaction, which was confirmed by Co-IP and PLA. Itga4 was specifically expressed in the apical papilla and upregulated during odontoblastic differentiation. Itga4 knockdown impaired odontoblastic differentiation and abolished SPP1-promoted odontogenesis.

Conclusions: Collectively, our findings elucidate a novel mechanism whereby sensory nerves orchestrate tooth root development by regulating progenitor cell fate through the SPP1/ITGA4 axis. This neuro-mesenchymal crosstalk provides insights for stem cell therapies and tooth root regeneration.

目的:干细胞/祖细胞是器官发生的关键细胞。感觉神经作为干细胞生态位的关键组成部分,分泌各种因子来调节干细胞/祖细胞的命运决定。在这里,我们利用牙根发育作为模型来探索感觉神经在这一调节过程中的作用,并阐明其潜在机制。方法:研究牙根发育过程中神经支配的时空动态特征。我们用三叉神经节条件培养基(TG-CM)处理小鼠牙乳头细胞(mDPCs),并采用tg -牙胚肾下共培养的方法评价感觉神经在成牙细胞分化和牙根形成中的功能。采用tg -牙胚肾下共培养法检测牙根形成过程中感觉神经功能的变化。在出生后第3.5天(PN3.5)和PN30天,对TG和磨牙的scRNA-seq进行综合分析,确定了潜在的神经源性因素,并通过负载重组蛋白或中和抗体珠的肾下移植进一步评估。CellChat用于分析tg和磨牙之间的细胞间通信。采用共免疫沉淀(Co-IP)和邻近连接法(PLA)证实分泌磷酸化蛋白1 (SPP1)和整合素α 4 (ITGA4)之间的相互作用。sirna介导的Itga4敲低评估了其在成牙细胞分化中的作用。结果:感觉神经纤维定位于PN3.5的顶端乳头和卵泡,并向冠部延伸。TG-CM与tg -牙胚在肾下共培养可促进成牙细胞分化和根伸长,表明感觉神经在根发育中起着不可或缺的作用。在PN3.5和PN30位点对TG和磨牙进行scRNA-seq综合分析,发现了多种感觉神经源性因子,包括SPP1、降钙素基因相关多肽(CGRP)和kit配体(KITL),它们在牙根发育中的功能在体内得到了验证。此外,CellChat分析显示SPP1-ITGA4是一个关键的配体-受体相互作用,这被Co-IP和PLA证实。Itga4在尖乳头中特异表达,在成牙细胞分化过程中表达上调。Itga4敲低会破坏成牙细胞分化,并消除spp1促进的成牙细胞形成。结论:总的来说,我们的研究结果阐明了一种新的机制,即感觉神经通过SPP1/ITGA4轴调节祖细胞的命运来协调牙根的发育。这种神经间充质间质串扰为干细胞治疗和牙根再生提供了新的见解。
{"title":"Sensory Nerves Regulate Odontoblast Differentiation via the SPP1/ITGA4 Axis During Tooth Root Development.","authors":"Huanyan Zuo, Jiahao Han, Jiawei Wu, Meng Liu, Yunjie Shuai, Diduo Tian, Fei Pei","doi":"10.1111/iej.70129","DOIUrl":"https://doi.org/10.1111/iej.70129","url":null,"abstract":"<p><strong>Aim: </strong>The stem/progenitor cell is crucial for organogenesis. Sensory nerves, as key components of the stem cell niche, secrete various factors to modulate stem/progenitor cell fate decision. Here, we utilised tooth root development as a model to explore the role of sensory nerves in this regulatory process and to elucidate the underlying mechanism.</p><p><strong>Methodology: </strong>Spatiotemporal dynamics of nerve innervation were characterised during tooth root development. We treated mouse dental papilla cells (mDPCs) with trigeminal ganglion-conditioned medium (TG-CM) and employed a subrenal co-culture of TG-tooth germ to evaluate sensory nerve function in odontoblastic differentiation and tooth root formation. A subrenal co-culture of TG-tooth germ was employed to detect sensory nerve function in tooth root formation. Integrated analysis of scRNA-seq from the TG and molar at post-natal day 3.5 (PN3.5) and PN30 identified potential nerve-derived factors, which were further assessed through subrenal transplantation with recombinant protein-loaded or neutralising antibody-loaded beads. CellChat was used to analyse cell-cell communication between TGs and molars. Co-immunoprecipitation (Co-IP) and proximity ligation assays (PLA) were used to confirm the interaction between secreted phosphoprotein 1 (SPP1) and integrin alpha 4 (ITGA4). The siRNA-mediated Itga4 knockdown assessed its role in odontoblastic differentiation.</p><p><strong>Results: </strong>Sensory nerve fibres localized to the apical papilla and follicle at PN3.5 and extended toward the crown. TG-CM and subrenal co-culture of TG-tooth germ enhanced odontoblast differentiation and root elongation, demonstrating the indispensable role of sensory nerves for proper root development. Integrated scRNA-seq analysis of TG and molar at PN3.5 and PN30 uncovered various sensory nerve-derived factors, including SPP1, calcitonin gene-related polypeptide (CGRP) and kit ligand (KITL), whose function in tooth root development was validated in vivo. Furthermore, CellChat analysis revealed SPP1-ITGA4 as a critical ligand-receptor interaction, which was confirmed by Co-IP and PLA. Itga4 was specifically expressed in the apical papilla and upregulated during odontoblastic differentiation. Itga4 knockdown impaired odontoblastic differentiation and abolished SPP1-promoted odontogenesis.</p><p><strong>Conclusions: </strong>Collectively, our findings elucidate a novel mechanism whereby sensory nerves orchestrate tooth root development by regulating progenitor cell fate through the SPP1/ITGA4 axis. This neuro-mesenchymal crosstalk provides insights for stem cell therapies and tooth root regeneration.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377313","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}
引用次数: 0
Lactylation-Driven Macrophage Polarisation Regulates Pulp Inflammation. 乳酸化驱动的巨噬细胞极化调节牙髓炎症。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-03-08 DOI: 10.1111/iej.70136
Ziting Wang, Wanli Xu, Tingyun Xu, Hang Zhao, Xiaolin Lyu, Leyi Chen, Wenjing Yi, Buling Wu, Wenan Xu
<p><strong>Aim: </strong>This study investigated the effects of lactate-induced lactylation in the inflammatory microenvironment of pulpitis and further explored the mechanism.</p><p><strong>Methodology: </strong>Lactate levels in pulpitis samples were quantified using a high-sensitivity assay. Histological, immunohistochemical, and immunofluorescence staining were conducted to evaluate lactylation, macrophage marker, pro-inflammatory, and anti-inflammatory markers. A time-course murine experimental pulpitis model (0-72 h) was established to characterise lactylation dynamics during inflammatory progression in pulpitis. An in vitro inflammatory dental pulp microenvironment model of THP-1 macrophages cocultured with LPS-pretreated dental pulp cells derived conditioned media (iCM) was developed to investigate lactate production and macrophage phenotypes. Transcriptomic profiling identified differentially expressed genes, with gene set enrichment analysis (GSEA) employed to assess the functions of differentially expressed genes. Transmission electron microscopy, quantitative real-time PCR (qRT-PCR), concurrent oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) were measured to evaluate the mitochondrial activity of iCM-pretreated macrophages. Mouse experimental pulpitis models treated with iCM were conducted to evaluate anti-inflammation and pro-healing properties by histological, immunohistochemical, and immunofluorescence staining.</p><p><strong>Results: </strong>Histological staining revealed that elevated lactate levels, increased Pan Kla expression, and upregulated extent of M2 phenotype macrophage infiltration in clinical pulpitis specimens. Notably, we identified a positive correlation between Pan Kla levels and M2 macrophage markers. In vitro inflammatory dental pulp microenvironment model, we demonstrated that M1 macrophages actively uptake lactate from iCM, leading to increased lactylation and subsequent M2-like polarisation. Importantly, we found that iCM could regulate polarisation of M1 macrophages via metabolic reprogramming, as evidenced by RNA sequencing. Our integrated analyses revealed significant mitochondrial structural remodelling, while metabolic flux assays demonstrated a characteristic shift from glycolytic metabolism to oxidative phosphorylation. This metabolic reprogramming was functionally linked to M2 polarisation, as evidenced by phenotypic marker analysis. Moreover, iCM treatment significantly downregulated pro-inflammatory cytokine (IL-6) while upregulating anti-inflammatory marker (CD206) in experimental pulpitis models.</p><p><strong>Conclusion: </strong>This study revealed that elevated lactate production in the inflammatory microenvironment roles as a mediator of immunometabolic crosstalk, bridging dental pulp cells-macrophage communication. And the mechanism involved in lactylation induced metabolic reprogramming. This helps to better understand the repair potential of inflamed dental pulp,
目的:研究乳酸诱导的乳酸化对牙髓炎炎症微环境的影响,并进一步探讨其机制。方法:采用高灵敏度测定法定量测定牙髓炎样品中的乳酸水平。采用组织学、免疫组织化学和免疫荧光染色来评估乳酸化、巨噬细胞标志物、促炎和抗炎标志物。建立小鼠实验性牙髓炎模型(0-72 h),以表征牙髓炎炎症进展过程中的乳酸化动力学。建立了THP-1巨噬细胞与lps预处理牙髓细胞衍生条件培养基(iCM)共培养的体外炎症牙髓微环境模型,以研究乳酸生成和巨噬细胞表型。转录组学分析鉴定了差异表达基因,并使用基因集富集分析(GSEA)来评估差异表达基因的功能。通过透射电镜、实时荧光定量PCR (qRT-PCR)、同步耗氧量(OCR)和细胞外酸化率(ECAR)来评估icm预处理巨噬细胞的线粒体活性。采用iCM治疗小鼠实验性牙髓炎模型,通过组织学、免疫组织化学和免疫荧光染色评价其抗炎和促愈合作用。结果:组织学染色显示临床牙髓炎标本中乳酸水平升高,Pan Kla表达升高,M2型巨噬细胞浸润程度上调。值得注意的是,我们发现Pan Kla水平与M2巨噬细胞标志物呈正相关。在体外炎症牙髓微环境模型中,我们证明了M1巨噬细胞积极地从iCM中摄取乳酸,导致乳酸化增加和随后的m2样极化。重要的是,我们发现iCM可以通过代谢重编程调节M1巨噬细胞的极化,正如RNA测序所证明的那样。我们的综合分析揭示了显著的线粒体结构重塑,而代谢通量分析显示了从糖酵解代谢到氧化磷酸化的特征转变。表型标记分析证明,这种代谢重编程在功能上与M2极化有关。此外,在实验性牙髓炎模型中,iCM治疗显著下调促炎细胞因子(IL-6),上调抗炎标志物(CD206)。结论:本研究揭示了炎症微环境中乳酸生成的升高是免疫代谢串音的中介,架起了牙髓细胞与巨噬细胞之间的沟通桥梁。以及乳酸化诱导代谢重编程的机制。这有助于更好地了解发炎牙髓的修复潜力,支持基于生物的保存方法。
{"title":"Lactylation-Driven Macrophage Polarisation Regulates Pulp Inflammation.","authors":"Ziting Wang, Wanli Xu, Tingyun Xu, Hang Zhao, Xiaolin Lyu, Leyi Chen, Wenjing Yi, Buling Wu, Wenan Xu","doi":"10.1111/iej.70136","DOIUrl":"https://doi.org/10.1111/iej.70136","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;This study investigated the effects of lactate-induced lactylation in the inflammatory microenvironment of pulpitis and further explored the mechanism.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methodology: &lt;/strong&gt;Lactate levels in pulpitis samples were quantified using a high-sensitivity assay. Histological, immunohistochemical, and immunofluorescence staining were conducted to evaluate lactylation, macrophage marker, pro-inflammatory, and anti-inflammatory markers. A time-course murine experimental pulpitis model (0-72 h) was established to characterise lactylation dynamics during inflammatory progression in pulpitis. An in vitro inflammatory dental pulp microenvironment model of THP-1 macrophages cocultured with LPS-pretreated dental pulp cells derived conditioned media (iCM) was developed to investigate lactate production and macrophage phenotypes. Transcriptomic profiling identified differentially expressed genes, with gene set enrichment analysis (GSEA) employed to assess the functions of differentially expressed genes. Transmission electron microscopy, quantitative real-time PCR (qRT-PCR), concurrent oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) were measured to evaluate the mitochondrial activity of iCM-pretreated macrophages. Mouse experimental pulpitis models treated with iCM were conducted to evaluate anti-inflammation and pro-healing properties by histological, immunohistochemical, and immunofluorescence staining.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Histological staining revealed that elevated lactate levels, increased Pan Kla expression, and upregulated extent of M2 phenotype macrophage infiltration in clinical pulpitis specimens. Notably, we identified a positive correlation between Pan Kla levels and M2 macrophage markers. In vitro inflammatory dental pulp microenvironment model, we demonstrated that M1 macrophages actively uptake lactate from iCM, leading to increased lactylation and subsequent M2-like polarisation. Importantly, we found that iCM could regulate polarisation of M1 macrophages via metabolic reprogramming, as evidenced by RNA sequencing. Our integrated analyses revealed significant mitochondrial structural remodelling, while metabolic flux assays demonstrated a characteristic shift from glycolytic metabolism to oxidative phosphorylation. This metabolic reprogramming was functionally linked to M2 polarisation, as evidenced by phenotypic marker analysis. Moreover, iCM treatment significantly downregulated pro-inflammatory cytokine (IL-6) while upregulating anti-inflammatory marker (CD206) in experimental pulpitis models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study revealed that elevated lactate production in the inflammatory microenvironment roles as a mediator of immunometabolic crosstalk, bridging dental pulp cells-macrophage communication. And the mechanism involved in lactylation induced metabolic reprogramming. This helps to better understand the repair potential of inflamed dental pulp, ","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377280","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}
引用次数: 0
Differential Expressions of Inflammatory, Dentinogenic, Regulatory, Proliferative and Stemness Genes in Non-Carious and Carious Human Dental Pulp Tissues: An Ex Vivo Proof-of-Concept Study. 非龋齿和龋齿人类牙髓组织中炎症、牙本质形成、调节、增殖和干性基因的差异表达:一项离体概念验证研究。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-03-08 DOI: 10.1111/iej.70134
Shelly Arora, Paul R Cooper, Lara T Friedlander, Jithendra T Ratnayake, Shakila B Rizwan, Benedict Seo, Alison M Rich, Haizal M Hussaini

Background: Dental caries demineralises the enamel and dentine of the teeth, and as infection progresses it can lead to pulpal inflammation, infection and severe pain.

Aim: To determine and compare the level of mRNA expression of Toll-like receptors ((TLR)-2, TLR-4 and TLR-9), tumour necrosis factor (TNF)-α, interleukins ((IL)-1α, IL-1β, IL-4, IL-6, IL-8, IL-17 and IL-23) as well as markers of dentinogenic (dentine matrix protein (DMP)-1, dentine sialophosphoprotein (DSPP)), regulatory (nuclear factor-kappa B (NF-κB1), mitogen activated protein kinase (MAPK1)), proliferative (mitogen activated protein kinase (MKi)) and stemness (sex determining region Y-box 2 (SOX2)) between non-carious and carious dental pulp tissues.

Methodology: This study undertook a comprehensive analysis of inflammatory markers including TLR-2, TLR-4, TLR-9, TNF-α, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-17 and IL-23, as well as markers of dentinogenic DMP-1, DSPP, NF-κB1, MAPK1, proliferative MKi and stemness SOX2 processes in healthy and carious pulp tissues using quantitative real-time reverse-transcription polymerase chain reaction.

Results: We found higher levels of TLR-2, TLR-4, IL-6, IL-8, IL-17A, IL-23A, along with NF-κB1 and MKi67 in the carious pulps (p < 0.05). The concurrent upregulation of IL-17A and IL-23A may suggest the activation of the IL-23/IL-17 signalling axis in the carious pulps, a point underreported in the literature.

Conclusion: These findings highlight the crucial role of the immune system in pulpal inflammation and potential implications in developing targeted molecular treatments, supporting the need for further translational research.

背景:龋齿使牙齿的牙釉质和牙本质脱矿,随着感染的进展,它会导致牙髓炎症、感染和剧烈疼痛。目的:测定并比较各组toll样受体(TLR -2、TLR-4、TLR-9)、肿瘤坏死因子(TNF)-α、白介素(IL)-1α、IL-1β、IL-4、IL-6、IL-8、IL-17、IL-23)、牙本质基质蛋白(DMP)-1、牙本质唾液磷酸蛋白(DSPP)、核因子κB (NF-κB1)、丝裂原活化蛋白激酶(MAPK1)、牙本质基质蛋白(DMP)-1、牙本质唾液磷酸蛋白(DSPP))、非龋齿牙髓组织和龋齿牙髓组织之间的增殖性(丝裂原活化蛋白激酶(MKi))和干性(性别决定区Y-box 2 (SOX2))。方法:本研究采用实时定量逆转录聚合酶链式反应,对健康和龋病牙髓组织中TLR-2、TLR-4、TLR-9、TNF-α、IL-1α、IL-1β、IL-4、IL-6、IL-8、IL-17、IL-23等炎症标志物以及牙本质原性DMP-1、DSPP、NF-κB1、MAPK1、增生性MKi、干性SOX2等标志物进行了综合分析。结果:我们发现龋牙髓中TLR-2、TLR-4、IL-6、IL-8、IL-17A、IL-23A以及NF-κB1和MKi67水平升高(p结论:这些发现突出了免疫系统在牙髓炎症中的重要作用,以及开发靶向分子治疗的潜在意义,支持进一步的转化研究的必要性。
{"title":"Differential Expressions of Inflammatory, Dentinogenic, Regulatory, Proliferative and Stemness Genes in Non-Carious and Carious Human Dental Pulp Tissues: An Ex Vivo Proof-of-Concept Study.","authors":"Shelly Arora, Paul R Cooper, Lara T Friedlander, Jithendra T Ratnayake, Shakila B Rizwan, Benedict Seo, Alison M Rich, Haizal M Hussaini","doi":"10.1111/iej.70134","DOIUrl":"https://doi.org/10.1111/iej.70134","url":null,"abstract":"<p><strong>Background: </strong>Dental caries demineralises the enamel and dentine of the teeth, and as infection progresses it can lead to pulpal inflammation, infection and severe pain.</p><p><strong>Aim: </strong>To determine and compare the level of mRNA expression of Toll-like receptors ((TLR)-2, TLR-4 and TLR-9), tumour necrosis factor (TNF)-α, interleukins ((IL)-1α, IL-1β, IL-4, IL-6, IL-8, IL-17 and IL-23) as well as markers of dentinogenic (dentine matrix protein (DMP)-1, dentine sialophosphoprotein (DSPP)), regulatory (nuclear factor-kappa B (NF-κB1), mitogen activated protein kinase (MAPK1)), proliferative (mitogen activated protein kinase (MKi)) and stemness (sex determining region Y-box 2 (SOX2)) between non-carious and carious dental pulp tissues.</p><p><strong>Methodology: </strong>This study undertook a comprehensive analysis of inflammatory markers including TLR-2, TLR-4, TLR-9, TNF-α, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-17 and IL-23, as well as markers of dentinogenic DMP-1, DSPP, NF-κB1, MAPK1, proliferative MKi and stemness SOX2 processes in healthy and carious pulp tissues using quantitative real-time reverse-transcription polymerase chain reaction.</p><p><strong>Results: </strong>We found higher levels of TLR-2, TLR-4, IL-6, IL-8, IL-17A, IL-23A, along with NF-κB1 and MKi67 in the carious pulps (p < 0.05). The concurrent upregulation of IL-17A and IL-23A may suggest the activation of the IL-23/IL-17 signalling axis in the carious pulps, a point underreported in the literature.</p><p><strong>Conclusion: </strong>These findings highlight the crucial role of the immune system in pulpal inflammation and potential implications in developing targeted molecular treatments, supporting the need for further translational research.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377310","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}
引用次数: 0
Beyond Novelty: What Makes Innovative Concepts in Endodontics Clinically Responsible? 超越新奇:是什么让牙髓学的创新概念具有临床责任?
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-03-07 DOI: 10.1111/iej.70128
Mohammed Turky, Ove A Peters, Paul V Abbott

The rapid emergence of novel concepts in endodontics-ranging from minimally invasive approaches to digital workflows and artificial intelligence-assisted decision-making-has significantly reshaped contemporary discourse within the specialty. While innovation is essential for progress, it is crucial to recognize that not all conceptual advances are inherently clinically responsible. The premature translation of inadequately validated concepts can expose patients to unforeseen risks and compromise long-term treatment outcomes. This article proposes a structured framework for defining clinical responsibility in the development of endodontic concepts. Grounded in key pillars-biological plausibility, proportional evidence, ethical accountability, and clinical applicability-this framework aims to strike a balance between fostering innovation and ensuring patient-centered care. By establishing clear criteria for responsible conceptual advancement, this paper seeks to guide authors, reviewers, and editors in critically evaluating emerging ideas before their integration into routine clinical practice.

牙髓学中新概念的迅速出现——从微创方法到数字工作流程和人工智能辅助决策——极大地重塑了该专业的当代话语。虽然创新对进步至关重要,但重要的是要认识到并非所有概念上的进步都具有内在的临床责任。未经充分验证的概念的过早翻译可能使患者面临不可预见的风险,并损害长期治疗结果。本文提出了一个结构化的框架来定义牙髓概念发展中的临床责任。该框架以生物合理性、比例证据、伦理责任和临床适用性等关键支柱为基础,旨在促进创新和确保以患者为中心的护理之间取得平衡。通过为负责任的概念进步建立明确的标准,本文旨在指导作者、审稿人和编辑在将新兴想法纳入常规临床实践之前对其进行批判性评估。
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引用次数: 0
Subgingival Microbial Signatures Associated With Apical Periodontitis Identified by Next Generation Sequencing and Predictive Modelling. 下一代测序和预测模型鉴定与根尖牙周炎相关的龈下微生物特征。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2026-03-07 DOI: 10.1111/iej.70131
Marcelo Britos, Elizabeth Pellegrini, Patricia Hernández-Ríos, Mauricio Garrido, Alejandra Fernández, Inmaculada Tomás, Rubén León, Alexandre Arredondo, Gerard Álvarez, Anilei Hoare Teuche, Marcela Hernández Ríos

Aims: To assess the relationship between endodontic and subgingival bacterial communities in individuals with apical periodontitis (AP), and to identify disease-associated subgingival microbial signatures. We propose that subgingival microbial communities exhibit a dysbiotic profile, defined by distinct bacterial signatures, which may provide complementary biological insights into AP.

Methods: In this cross-sectional study, DNA was extracted from paired endodontic and subgingival samples from mesiobuccal sites of first molars in patients with AP (n = 25 sample pairs), and from subgingival samples from the same sites in healthy individuals (n = 34). Microbiota was explored using 16S rRNA sequencing. Alpha and beta diversity metrics were calculated. Differentially abundant taxa were identified using LEfSe. Random forest models based on the bacterial counts observed in the subgingival samples were trained to classify the individuals with AP from the controls.

Results: Within AP individuals, the subgingival communities differed from those present in root canals. Subgingival communities exhibited higher alpha diversity than root canal communities, irrespective of the clinical diagnosis (p < 0.001). Subgingival microbial communities in AP individuals exhibited a dysbiotic profile associated with enrichment of anaerobic and inflammophilic species (p < 0.05). Beta diversity analyses showed compositional differences between AP and control individuals, with Jaccard distance reaching statistical significance (p < 0.05), and Bray-Curtis indicating a borderline effect (p = 0.07). The best predictive model (Streptococcus sanguinis and Prevotella maculosa) achieved an accuracy of 89.8%, sensitivity of 80%, specificity of 97%, precision of 95.2%, and an AUC of 0.98.

Conclusions: Subgingival profiles from AP individuals are distinct from those in healthy controls, showing AP-associated dysbiosis. Specific subgingival bacterial signatures achieved high diagnostic accuracy, supporting the potential broader impact of AP on the subgingival microbiota.

目的:评估根尖牙周炎(AP)患者牙髓和牙龈下细菌群落之间的关系,并确定与疾病相关的牙龈下微生物特征。我们认为,牙龈下的微生物群落表现出一种不同的细菌特征,这可能为AP提供补充的生物学见解。方法:在这项横断面研究中,从AP患者第一磨牙中颊部的成对牙髓和牙龈下样本(n = 25对样本)和健康个体相同部位的牙龈下样本(n = 34)中提取DNA。采用16S rRNA测序对微生物区系进行研究。计算了α和β多样性指标。利用LEfSe鉴定出差异丰富的分类群。随机森林模型基于在龈下样本中观察到的细菌数量进行训练,以从对照组中分类患有AP的个体。结果:在AP个体中,牙龈下群落与根管中存在的群落不同。与临床诊断无关,牙龈下菌群比根管菌群表现出更高的α多样性(p结论:AP个体的牙龈下菌群与健康对照者不同,显示AP相关的生态失调。特异的龈下细菌特征获得了很高的诊断准确性,支持AP对龈下微生物群的潜在广泛影响。
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引用次数: 0
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International endodontic journal
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