Shuntaro Yamada, Katerina Holomkova, Åshild Johansen, Masoumeh Jahani Kadousaraei, Niyaz Al-Sharabi, Francesco Torelli, Pierfrancesco Pagella, Ana Angelova Volponi, Hiroshi Egusa, Inge Fristad, Kamal Mustafa
Aim
This study aimed to evaluate whether human dental pulp stem cells (DPSCs), after long-term biobanking (7–8 years), retain their pro-angiogenic properties and can be used to engineer vascularised tissues, addressing their potential for clinical translation in regenerative dentistry.
Methodology
Cryopreserved DPSCs from adolescent donors were recovered from biobanking and characterised for chromosomal integrity, MSC immunophenotype and multipotency. After conditioning in pro-angiogenic conditions in vitro, gene and protein expression were analysed by RT-qPCR array, flow cytometry and high-throughput immunophenotyping. Functional angiogenic capacity was assessed via in vitro tube formation, ex ovo CAM implantation assay, organ-on-chip perfusion model and long-term culture (45 days) in clinical-grade GelMA hydrogels, with and without HUVECs.
Results
Biobanked DPSCs retained MSC identity and multi-lineage differentiation potential. Pro-angiogenic/endothelial conditioning enhanced the expression of angiogenic/endothelial genes (PECAM1, VEGFR2, NRP1, ACE), yet most cells maintained a pericyte-like phenotype. Both naive and endothelial-conditioned DPSCs (i.e., naiveDPSCs and endoDPSCs, respectively) significantly enhanced vascular ingrowth in the CAM model. In the organ-on-chip system, naiveDPSCs formed perfusable vasculature with HUVECs and differentiated into perivascular cell types. Most notably, endoDPSCs alone successfully generated vascularised tissue with both CD31(+) and αSMA(+) cells present in GelMA hydrogels after prolonged stimulation.
Conclusion
Long-term biobanked DPSCs preserve their angiogenic potential and, following extended endothelial induction, can independently generate vascularised tissue in 3D in vitro culture models. This is the first report demonstrating the comprehensive pro-angiogenic characterisation and the feasibility of using biobanked DPSCs for vascularised tissue engineering, highlighting their strong clinical applicability for future regenerative therapies.
{"title":"Long-Term Biobanked Dental Pulp Stem Cells Retain Angiogenic Potential for Vascularised Tissue Engineering—Laboratory Investigation","authors":"Shuntaro Yamada, Katerina Holomkova, Åshild Johansen, Masoumeh Jahani Kadousaraei, Niyaz Al-Sharabi, Francesco Torelli, Pierfrancesco Pagella, Ana Angelova Volponi, Hiroshi Egusa, Inge Fristad, Kamal Mustafa","doi":"10.1111/iej.70036","DOIUrl":"10.1111/iej.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to evaluate whether human dental pulp stem cells (DPSCs), after long-term biobanking (7–8 years), retain their pro-angiogenic properties and can be used to engineer vascularised tissues, addressing their potential for clinical translation in regenerative dentistry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Cryopreserved DPSCs from adolescent donors were recovered from biobanking and characterised for chromosomal integrity, MSC immunophenotype and multipotency. After conditioning in pro-angiogenic conditions in vitro, gene and protein expression were analysed by RT-qPCR array, flow cytometry and high-throughput immunophenotyping. Functional angiogenic capacity was assessed via in vitro tube formation, <i>ex ovo</i> CAM implantation assay, organ-on-chip perfusion model and long-term culture (45 days) in clinical-grade GelMA hydrogels, with and without HUVECs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Biobanked DPSCs retained MSC identity and multi-lineage differentiation potential. Pro-angiogenic/endothelial conditioning enhanced the expression of angiogenic/endothelial genes (PECAM1, VEGFR2, NRP1, ACE), yet most cells maintained a pericyte-like phenotype. Both naive and endothelial-conditioned DPSCs (i.e., naiveDPSCs and endoDPSCs, respectively) significantly enhanced vascular ingrowth in the CAM model. In the organ-on-chip system, naiveDPSCs formed perfusable vasculature with HUVECs and differentiated into perivascular cell types. Most notably, endoDPSCs alone successfully generated vascularised tissue with both CD31(+) and αSMA(+) cells present in GelMA hydrogels after prolonged stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Long-term biobanked DPSCs preserve their angiogenic potential and, following extended endothelial induction, can independently generate vascularised tissue in 3D in vitro culture models. This is the first report demonstrating the comprehensive pro-angiogenic characterisation and the feasibility of using biobanked DPSCs for vascularised tissue engineering, highlighting their strong clinical applicability for future regenerative therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 1","pages":"105-118"},"PeriodicalIF":7.1,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Venkateshbabu Nagendrababu, Asiya Sameer Mujawar, Nandini Suresh, Francesc Abella Sans, Michael Hülsmann, Frank C. Setzer, Paul M. H. Dummer
Dens invaginatus (DI) is a dental developmental anomaly that arises when the enamel organ folds into the dental papilla during the morpho-differentiation phase of tooth development (Hülsmann 1997). Several factors may contribute to this disruption in enamel organ development, including genetic predisposition (Sarraf-Shirazi et al. 2010), physical trauma, infections, and irregular tooth bud growth (Hülsmann 1997). Overall prevalence rates of DI vary widely, ranging from 0.39% to 13.5% of teeth (Capar et al. 2015; Hegde et al. 2022). However, more recent data utilising three-dimensional (3D) imaging techniques suggest an overall global prevalence of approximately 7% across all teeth, with no significant difference between males and females (Dos Alves Santos et al. 2023). The maxillary lateral incisors are the most frequently affected teeth, exhibiting a prevalence of approximately 5%, with unilateral presentations being more common (Dos Alves Santos et al. 2023).
The development and validation of a new 3D classification for DI will address the shortcomings of traditional systems by incorporating CBCT-based data and clinically relevant parameters. It will ultimately result in enhanced patient and clinician-reported outcomes by providing a standardised and comprehensive approach to diagnosing and managing this complex anomaly. This initiative is indicative of a more comprehensive endeavour to establish a more precise and clinically meaningful framework for future research and practice in the management of this complex anomaly. The authors acknowledge that the accuracy of CBCT images used to define DI is influenced by factors such as field of view, resolution, and voxel size.
All the authors made substantial contributions to the manuscript. All the authors have read and approved the final version of the manuscript.
The authors declare no conflicts of interest.
The authors have nothing to report.
内凹牙是一种牙齿发育异常，发生于牙齿发育的形态分化阶段，牙釉质器官折叠成牙乳头时（h lsmann 1997）。有几个因素可能导致牙釉质器官发育的破坏，包括遗传易感（Sarraf-Shirazi et al. 2010）、身体创伤、感染和不规则的牙芽生长（h lsmann 1997）。残牙的总体患病率差异很大，从0.39%到13.5%不等（Capar et al. 2015; Hegde et al. 2022）。然而，利用三维（3D）成像技术的最新数据表明，全球所有牙齿的总体患病率约为7%，男性和女性之间没有显着差异（Dos Alves Santos等人，2023）。上颌侧门牙是最常受影响的牙齿，患病率约为5%，单侧表现更为常见（Dos Alves Santos et al. 2023）。通过结合基于cbct的数据和临床相关参数，新的DI 3D分类的开发和验证将解决传统系统的缺点。通过提供一种标准化和全面的方法来诊断和管理这种复杂的异常，最终将提高患者和临床报告的结果。这一举措表明，在未来的研究和治疗这一复杂异常的实践中，需要更全面地努力建立一个更精确、更有临床意义的框架。作者承认，用于定义DI的CBCT图像的准确性受到视场、分辨率和体素大小等因素的影响。所有的作者都对这份手稿作出了很大的贡献。所有作者都阅读并认可了稿件的最终版本。作者声明无利益冲突。作者没有什么可报告的。
{"title":"A Protocol for the Development of a New Three-Dimensional Classification of Dens Invaginatus Using Cone Beam Computed Tomography Imaging","authors":"Venkateshbabu Nagendrababu, Asiya Sameer Mujawar, Nandini Suresh, Francesc Abella Sans, Michael Hülsmann, Frank C. Setzer, Paul M. H. Dummer","doi":"10.1111/iej.70035","DOIUrl":"10.1111/iej.70035","url":null,"abstract":"<p>Dens invaginatus (DI) is a dental developmental anomaly that arises when the enamel organ folds into the dental papilla during the morpho-differentiation phase of tooth development (Hülsmann <span>1997</span>). Several factors may contribute to this disruption in enamel organ development, including genetic predisposition (Sarraf-Shirazi et al. <span>2010</span>), physical trauma, infections, and irregular tooth bud growth (Hülsmann <span>1997</span>). Overall prevalence rates of DI vary widely, ranging from 0.39% to 13.5% of teeth (Capar et al. <span>2015</span>; Hegde et al. <span>2022</span>). However, more recent data utilising three-dimensional (3D) imaging techniques suggest an overall global prevalence of approximately 7% across all teeth, with no significant difference between males and females (Dos Alves Santos et al. <span>2023</span>). The maxillary lateral incisors are the most frequently affected teeth, exhibiting a prevalence of approximately 5%, with unilateral presentations being more common (Dos Alves Santos et al. <span>2023</span>).</p><p>The development and validation of a new 3D classification for DI will address the shortcomings of traditional systems by incorporating CBCT-based data and clinically relevant parameters. It will ultimately result in enhanced patient and clinician-reported outcomes by providing a standardised and comprehensive approach to diagnosing and managing this complex anomaly. This initiative is indicative of a more comprehensive endeavour to establish a more precise and clinically meaningful framework for future research and practice in the management of this complex anomaly. The authors acknowledge that the accuracy of CBCT images used to define DI is influenced by factors such as field of view, resolution, and voxel size.</p><p>All the authors made substantial contributions to the manuscript. All the authors have read and approved the final version of the manuscript.</p><p>The authors declare no conflicts of interest.</p><p>The authors have nothing to report.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 1","pages":"19-22"},"PeriodicalIF":7.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. C. Georgiou, G. R. van der Ploeg, J. A. Westerhuis, S. V. van der Waal, A. Heintz-Buschart, A. K. Smilde, B. W. Brandt
Aim
This study aimed to investigate systemic inflammatory responses in individuals with apical periodontitis (AP) compared to age-matched healthy controls, using advanced multiway modelling techniques. We examined associations between inflammatory mediators, age, gender, symptomatic status, and the microbial composition and function to better understand host–microbe interactions in AP.
Methods
We conducted a longitudinal study with 53 participants (27 with AP, 26 controls) aged 18 to 80. Blood inflammatory mediators were measured at multiple time points. Root canal microbiome and potential functions were analysed using 16S rRNA gene sequencing. Data were analysed using Parallel Factor Analysis (PARAFAC) and Advanced Coupled Matrix and Tensor Factorization (ACMTF) to capture time-resolved variation.
Results
PARAFAC revealed that IL-4 levels were significantly elevated in AP cases, suggesting a role for adaptive immune activation. Age strongly influenced markers such as CRP, TNF-α, and VEGF. Symptomatic AP cases showed higher CRP and lower OPG levels, indicating more active inflammation and altered bone metabolism. ACMTF identified associations between specific taxa (e.g., Parvimonas micra, Streptococcus mutans) and inflammatory mediators, with functional analysis highlighting enriched pathways like sphingolipid signalling in asymptomatic cases.
Conclusion
This study provides novel insights into the systemic immune profile of individuals with AP. IL-4 and bone metabolism markers may serve as potential biomarkers for distinguishing AP status. Our findings support the relevance of systemic inflammation in endodontic infections and underscore the value of multi-marker, multivariate approaches to better characterise disease progression and host–microbiome interactions. Such insights could contribute to improved risk stratification and personalised management in dental and systemic health contexts.
{"title":"Modelling of the Systemic Inflammatory Host Response in Relation to the Microbiome of the Endodontic Infection","authors":"A. C. Georgiou, G. R. van der Ploeg, J. A. Westerhuis, S. V. van der Waal, A. Heintz-Buschart, A. K. Smilde, B. W. Brandt","doi":"10.1111/iej.70023","DOIUrl":"10.1111/iej.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to investigate systemic inflammatory responses in individuals with apical periodontitis (AP) compared to age-matched healthy controls, using advanced multiway modelling techniques. We examined associations between inflammatory mediators, age, gender, symptomatic status, and the microbial composition and function to better understand host–microbe interactions in AP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a longitudinal study with 53 participants (27 with AP, 26 controls) aged 18 to 80. Blood inflammatory mediators were measured at multiple time points. Root canal microbiome and potential functions were analysed using 16S rRNA gene sequencing. Data were analysed using Parallel Factor Analysis (PARAFAC) and Advanced Coupled Matrix and Tensor Factorization (ACMTF) to capture time-resolved variation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PARAFAC revealed that IL-4 levels were significantly elevated in AP cases, suggesting a role for adaptive immune activation. Age strongly influenced markers such as CRP, TNF-α, and VEGF. Symptomatic AP cases showed higher CRP and lower OPG levels, indicating more active inflammation and altered bone metabolism. ACMTF identified associations between specific taxa (e.g., <i>Parvimonas micra</i>, <i>Streptococcus mutans</i>) and inflammatory mediators, with functional analysis highlighting enriched pathways like sphingolipid signalling in asymptomatic cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides novel insights into the systemic immune profile of individuals with AP. IL-4 and bone metabolism markers may serve as potential biomarkers for distinguishing AP status. Our findings support the relevance of systemic inflammation in endodontic infections and underscore the value of multi-marker, multivariate approaches to better characterise disease progression and host–microbiome interactions. Such insights could contribute to improved risk stratification and personalised management in dental and systemic health contexts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"58 12","pages":"1926-1939"},"PeriodicalIF":7.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carolina Sayuri Wajima, Carolina de Barros Morais Cardoso, Caroline Anselmi, Renan Dal-Fabbro, Murilo Catelani Ferraz, Cristiane Cantiga da Silva, Paulo César Ciarlini, Edilson Ervolino, Marco Cícero Bottino, Luciano Tavares Angelo Cintra
<div> <section> <h3> Aim</h3> <p>Apical periodontitis (AP) is a highly prevalent chronic inflammatory disease that can exert systemic effects by releasing biochemical mediators that initiate and regulate the immune response. Yerba Mate (<i>Ilex paraguariensis</i>, YM), a popular plant broadly consumed in South America, is rich in biologically active compounds known for their therapeutic potential. This study assessed Y's in vitro cytocompatibility, anti-osteoclastogenic and immunomodulatory effects on oral stem cells and macrophages, as well as its in vivo potential to reduce AP severity and systemic side effects.</p> </section> <section> <h3> Methodology</h3> <p>In vitro, instant powdered YM was dissolved in distilled water, filtered and diluted in culture media to final concentrations ranging from 1 to 200 μg/mL. Cell viability and pro-inflammatory cytokine release (IL-1α, IL-6, TNF-α) were assessed in human exfoliated deciduous teeth stem cells. The NF-κB pathway and anti-osteoclastogenic activity were evaluated using a luciferase reporter assay and TRAP staining in RAW 264.7. Forty male Wistar rats were divided into control (C), YM-treated(YM), AP-induced (AP) and AP with YM treatment (AP + YM). YM treatment (20 Mg/Kg/Day) was administered via gavage for 58 days. AP was induced after 28 days of YM intake, and the animals were euthanised 30 days later. In serum, systemic redox state was assessed via total antioxidant capacity (TAC) and thiobarbituric acid reactive substances (TBARS). Histological and immunohistochemical analyses evaluated inflammation, cytokine expression (TNF-α, IL-6, IL-10 and IL-17) and bone resorption markers. Micro-CT quantified alveolar bone loss. Data were analysed at <i>p</i> < 0.05.</p> </section> <section> <h3> Results</h3> <p>YM treatment demonstrated significant anti-inflammatory, antioxidant and bone-protective effects. In vitro, YM-supported cell viability, reduced TNF-α and IL-1α, inhibited NF-κB activation and suppressed osteoclastogenesis. In vivo, YM treatment restored systemic antioxidant capacity and reduced lipid peroxidation, mitigating AP-induced oxidative stress. Furthermore, YM intake attenuated the local inflammatory response and reduced the bone resorptive activity associated with AP.</p> </section> <section> <h3> Conclusion</h3> <p>In vitro, YM suppressed pro-inflammatory cytokines and NF-κB, inhibited osteoclastogenesis and was cytocompatible. In vivo, it reversed AP-induced redox state and reduced inflammation and bone resorption, suggesting therapeutic promise.</p> </section>
{"title":"Yerba Mate (Ilex paraguariensis A. St.-Hil.) Reduces Oxidative Stress and Bone Resorption in Apical Periodontitis","authors":"Carolina Sayuri Wajima, Carolina de Barros Morais Cardoso, Caroline Anselmi, Renan Dal-Fabbro, Murilo Catelani Ferraz, Cristiane Cantiga da Silva, Paulo César Ciarlini, Edilson Ervolino, Marco Cícero Bottino, Luciano Tavares Angelo Cintra","doi":"10.1111/iej.70031","DOIUrl":"10.1111/iej.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Apical periodontitis (AP) is a highly prevalent chronic inflammatory disease that can exert systemic effects by releasing biochemical mediators that initiate and regulate the immune response. Yerba Mate (<i>Ilex paraguariensis</i>, YM), a popular plant broadly consumed in South America, is rich in biologically active compounds known for their therapeutic potential. This study assessed Y's in vitro cytocompatibility, anti-osteoclastogenic and immunomodulatory effects on oral stem cells and macrophages, as well as its in vivo potential to reduce AP severity and systemic side effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>In vitro, instant powdered YM was dissolved in distilled water, filtered and diluted in culture media to final concentrations ranging from 1 to 200 μg/mL. Cell viability and pro-inflammatory cytokine release (IL-1α, IL-6, TNF-α) were assessed in human exfoliated deciduous teeth stem cells. The NF-κB pathway and anti-osteoclastogenic activity were evaluated using a luciferase reporter assay and TRAP staining in RAW 264.7. Forty male Wistar rats were divided into control (C), YM-treated(YM), AP-induced (AP) and AP with YM treatment (AP + YM). YM treatment (20 Mg/Kg/Day) was administered via gavage for 58 days. AP was induced after 28 days of YM intake, and the animals were euthanised 30 days later. In serum, systemic redox state was assessed via total antioxidant capacity (TAC) and thiobarbituric acid reactive substances (TBARS). Histological and immunohistochemical analyses evaluated inflammation, cytokine expression (TNF-α, IL-6, IL-10 and IL-17) and bone resorption markers. Micro-CT quantified alveolar bone loss. Data were analysed at <i>p</i> < 0.05.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>YM treatment demonstrated significant anti-inflammatory, antioxidant and bone-protective effects. In vitro, YM-supported cell viability, reduced TNF-α and IL-1α, inhibited NF-κB activation and suppressed osteoclastogenesis. In vivo, YM treatment restored systemic antioxidant capacity and reduced lipid peroxidation, mitigating AP-induced oxidative stress. Furthermore, YM intake attenuated the local inflammatory response and reduced the bone resorptive activity associated with AP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In vitro, YM suppressed pro-inflammatory cytokines and NF-κB, inhibited osteoclastogenesis and was cytocompatible. In vivo, it reversed AP-induced redox state and reduced inflammation and bone resorption, suggesting therapeutic promise.</p>\u0000 </section>\u0000 ","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 1","pages":"91-104"},"PeriodicalIF":7.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie Mora, Jonathan Nguyen, Siddarth Mehta, Nader Mehra, Asgeir Sigurdsson, Min-Wen Fu, Nihan Gencerliler, Matthew Malek
Aim
Periapical Osteoperiostitis (PO) is an inflammatory reaction of the periosteum located on the maxillary sinus floor, characterised by reactionary deposition of bone caused by periradicular disease of the maxillary posterior teeth. Radiographically, PO presents as a radiopaque ‘halo’ over the involved root(s). There is a gap in the literature regarding the prevalence and predisposing factors of PO. This study aims (1) to evaluate the prevalence of PO in maxillary posterior teeth amongst patients at NYU College of Dentistry, Department of Endodontics, and (2) to identify predisposing factors associated with PO.
Methodology
A chart review and cone-beam computed tomography (CBCT) evaluation were conducted at NYU College of Dentistry from 2016 to 2021. Initially, 586 scans were screened, and 335 scans were included. The presence of PO, mucositis, sinus perforation, age, sex, pulpal and periapical diagnosis, size of the lesion, the vertical and horizontal distance between the sinus floor and roots, number of roots with apical lesions, type of tooth, and iatrogenic errors during treatment were recorded. Data were analysed using chi-square, Fisher's tests and logistic regression.
Results
Of the 335 CBCT scans included, 98 scans (29.3%) presented with PO. The presence of mucositis was associated with 3.37 times higher odds of PO than those without mucositis. Each incremental increase in the size of the lesion (CBCTPAI) was associated with a 2.51 increase in the odds of PO occurrence, and the vertical distance between the sinus and roots was statistically significant (p < 0.001).
Conclusion
The prevalence of PO in this study was higher than previously reported. Three factors were significantly associated with PO: the presence of mucositis, the size of the lesion, and the vertical distance between the sinus and roots.
{"title":"Prevalence and Predisposing Factors of Periapical Osteoperiostitis: A Retrospective Cross-Sectional Study","authors":"Marie Mora, Jonathan Nguyen, Siddarth Mehta, Nader Mehra, Asgeir Sigurdsson, Min-Wen Fu, Nihan Gencerliler, Matthew Malek","doi":"10.1111/iej.70033","DOIUrl":"10.1111/iej.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Periapical Osteoperiostitis (PO) is an inflammatory reaction of the periosteum located on the maxillary sinus floor, characterised by reactionary deposition of bone caused by periradicular disease of the maxillary posterior teeth. Radiographically, PO presents as a radiopaque ‘halo’ over the involved root(s). There is a gap in the literature regarding the prevalence and predisposing factors of PO. This study aims (1) to evaluate the prevalence of PO in maxillary posterior teeth amongst patients at NYU College of Dentistry, Department of Endodontics, and (2) to identify predisposing factors associated with PO.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>A chart review and cone-beam computed tomography (CBCT) evaluation were conducted at NYU College of Dentistry from 2016 to 2021. Initially, 586 scans were screened, and 335 scans were included. The presence of PO, mucositis, sinus perforation, age, sex, pulpal and periapical diagnosis, size of the lesion, the vertical and horizontal distance between the sinus floor and roots, number of roots with apical lesions, type of tooth, and iatrogenic errors during treatment were recorded. Data were analysed using chi-square, Fisher's tests and logistic regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 335 CBCT scans included, 98 scans (29.3%) presented with PO. The presence of mucositis was associated with 3.37 times higher odds of PO than those without mucositis. Each incremental increase in the size of the lesion (CBCTPAI) was associated with a 2.51 increase in the odds of PO occurrence, and the vertical distance between the sinus and roots was statistically significant (<i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The prevalence of PO in this study was higher than previously reported. Three factors were significantly associated with PO: the presence of mucositis, the size of the lesion, and the vertical distance between the sinus and roots.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 1","pages":"38-46"},"PeriodicalIF":7.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040125","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}
This study aimed to quantify the effect of chitosan-hydroxyapatite precursor nanocomplexes (C-HA) on void reduction in the root canal system and isthmus regions, characterise void distribution patterns and assess sealer-dentin interface adaptation post-conditioning.
Methodology
Vertucci type II and Yin type IV mesial root canals from 24 extracted mandibular first molars were randomly divided into two groups (n = 12): (1) C-HA conditioned and (2) control (deionised water). All canals underwent standardised preparation using ProTaper Next files with 3% NaOCl irrigation (2 mL per file change) and final irrigation with 17% EDTA (5 mL, sonic activation) followed by 3% NaOCl (5 mL) and a final deionised water rinse (5 mL). Before obturation, the C-HA group received 5 min of C-HA solution (2 mg/mL) treatment with active agitation by ProTaper Next X2 gutta-percha cone, while the control group received equivalent water treatment. Canals were obturated using the single-cone technique with Ceraseal. High-resolution Micro-CT (8.6 μm voxel size) quantified void percentages in the entire canal system and isthmus regions, with analysis stratified by coronal, middle and apical thirds. Selected specimens underwent SEM evaluation of interfacial adaptation. Statistical analysis used the independent samples t-test, two-way ANOVA with Tukey's post hoc tests (α = 0.05), and Fisher's exact test.
Results
No significant differences related to the canal/isthmus pre-treatment volumes and isthmus characteristics were noted between the two groups. Micro-CT analysis revealed significantly lower void percentages in C-HA-treated canals compared to controls (9.21% vs. 19.01% in the entire canal system and 19.07% vs. 55.65% in the isthmus regions, p < 0.001). Analysis of the void distribution patterns further demonstrated statistically significant differences between the groups in the cervical and middle root thirds (p < 0.05). SEM evaluation showed continuous, gap-free interfaces with bioactive mineralization in C-HA-treated canals, contrasting with discontinuous adaptation and sparse precipitates in controls.
Conclusion
C-HA dentine conditioning significantly improved obturation quality with Ceraseal bioceramic sealer by reducing voids in isthmus regions and enhancing sealer-dentin interfacial adaptation.
{"title":"Enhancing the Quality of Single Cone Obturation Using Hydroxyapatite Precursor Grafted Nanocomplex for Dentine Conditioning: An In Vitro Study","authors":"Eissa Sameer Bunashi, Mingxin Hu, Angeline Hui Cheng Lee, Chengfei Zhang, Anil Kishen, Jeffrey Wen Wei Chang","doi":"10.1111/iej.70034","DOIUrl":"10.1111/iej.70034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to quantify the effect of chitosan-hydroxyapatite precursor nanocomplexes (C-HA) on void reduction in the root canal system and isthmus regions, characterise void distribution patterns and assess sealer-dentin interface adaptation post-conditioning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Vertucci type II and Yin type IV mesial root canals from 24 extracted mandibular first molars were randomly divided into two groups (<i>n</i> = 12): (1) C-HA conditioned and (2) control (deionised water). All canals underwent standardised preparation using ProTaper Next files with 3% NaOCl irrigation (2 mL per file change) and final irrigation with 17% EDTA (5 mL, sonic activation) followed by 3% NaOCl (5 mL) and a final deionised water rinse (5 mL). Before obturation, the C-HA group received 5 min of C-HA solution (2 mg/mL) treatment with active agitation by ProTaper Next X2 gutta-percha cone, while the control group received equivalent water treatment. Canals were obturated using the single-cone technique with Ceraseal. High-resolution Micro-CT (8.6 μm voxel size) quantified void percentages in the entire canal system and isthmus regions, with analysis stratified by coronal, middle and apical thirds. Selected specimens underwent SEM evaluation of interfacial adaptation. Statistical analysis used the independent samples <i>t</i>-test, two-way ANOVA with Tukey's post hoc tests (<i>α</i> = 0.05), and Fisher's exact test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant differences related to the canal/isthmus pre-treatment volumes and isthmus characteristics were noted between the two groups. Micro-CT analysis revealed significantly lower void percentages in C-HA-treated canals compared to controls (9.21% vs. 19.01% in the entire canal system and 19.07% vs. 55.65% in the isthmus regions, <i>p</i> < 0.001). Analysis of the void distribution patterns further demonstrated statistically significant differences between the groups in the cervical and middle root thirds (<i>p</i> < 0.05). SEM evaluation showed continuous, gap-free interfaces with bioactive mineralization in C-HA-treated canals, contrasting with discontinuous adaptation and sparse precipitates in controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>C-HA dentine conditioning significantly improved obturation quality with Ceraseal bioceramic sealer by reducing voids in isthmus regions and enhancing sealer-dentin interfacial adaptation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 1","pages":"177-188"},"PeriodicalIF":7.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad A. Sabeti, Keyvan Nikghalb, Reza Pakzad, Ashraf F. Fouad
Introduction
Accurate diagnosis of pulpal health is crucial to identify the most effective therapeutic approach. However, differentiating pulpal conditions, which may require different treatment approaches, remains a challenge. This study aimed to address this gap by investigating the protein levels of 17 inflammatory biomarkers simultaneously in the dental pulp with different clinical diagnoses.
Methods
This study employed a cross-sectional exploratory design, enrolling 64 adult patients. After obtaining ethical approval, researchers conducted clinical and radiographic examinations to categorise teeth into four diagnostic groups: normal pulp, reversible pulpitis, symptomatic irreversible pulpitis and asymptomatic irreversible pulpitis. Pulpal blood samples were then collected and analysed using Luminex technology to measure the levels of inflammatory proteins and matrix metalloproteinases (MMPs). Statistical analyses, including the Mann–Whitney U test and Spearman's rank correlation, were used to compare the levels of these markers across the different diagnoses and to assess their correlation with patient symptoms.
Results
The study revealed significant increases in several inflammatory proteins, including IL-4, IL-8, MCP-1, MIP-1α, RANTES and MMP-9, in both types of irreversible pulpitis cases compared with other diagnostic categories p < 0.05. These elevated levels exhibited positive correlations with patient-reported pain scores, instances of spontaneous pain and bleeding times. Notably, only IL-4 and IL-7 exhibited correlations with prolonged bleeding times (over 10 min) p < 0.05, while IL-1α and MMP-2 were associated with shorter bleeding times (under 10 min) p < 0.05. Additionally, IL-8 and MCP-1 levels were significantly associated with positive palpation findings p < 0.05, whereas MIP-1α and MMP-1 were correlated with positive percussion results p < 0.05.
Conclusion
Differential specific inflammatory potential biomarker levels may differentiate pulpal disease states. Integrating molecular diagnostics into longitudinal clinical trials and eventually into routine endodontic practice, could revolutionise treatment decisions.
{"title":"The Relationship Between Pulpal Diagnostic Conditions and Potential Inflammatory Biomarkers","authors":"Mohammad A. Sabeti, Keyvan Nikghalb, Reza Pakzad, Ashraf F. Fouad","doi":"10.1111/iej.70030","DOIUrl":"10.1111/iej.70030","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Accurate diagnosis of pulpal health is crucial to identify the most effective therapeutic approach. However, differentiating pulpal conditions, which may require different treatment approaches, remains a challenge. This study aimed to address this gap by investigating the protein levels of 17 inflammatory biomarkers simultaneously in the dental pulp with different clinical diagnoses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study employed a cross-sectional exploratory design, enrolling 64 adult patients. After obtaining ethical approval, researchers conducted clinical and radiographic examinations to categorise teeth into four diagnostic groups: normal pulp, reversible pulpitis, symptomatic irreversible pulpitis and asymptomatic irreversible pulpitis. Pulpal blood samples were then collected and analysed using Luminex technology to measure the levels of inflammatory proteins and matrix metalloproteinases (MMPs). Statistical analyses, including the Mann–Whitney <i>U</i> test and Spearman's rank correlation, were used to compare the levels of these markers across the different diagnoses and to assess their correlation with patient symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study revealed significant increases in several inflammatory proteins, including IL-4, IL-8, MCP-1, MIP-1α, RANTES and MMP-9, in both types of irreversible pulpitis cases compared with other diagnostic categories <i>p</i> < 0.05. These elevated levels exhibited positive correlations with patient-reported pain scores, instances of spontaneous pain and bleeding times. Notably, only IL-4 and IL-7 exhibited correlations with prolonged bleeding times (over 10 min) <i>p</i> < 0.05, while IL-1α and MMP-2 were associated with shorter bleeding times (under 10 min) <i>p</i> < 0.05. Additionally, IL-8 and MCP-1 levels were significantly associated with positive palpation findings <i>p</i> < 0.05, whereas MIP-1α and MMP-1 were correlated with positive percussion results <i>p</i> < 0.05.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Differential specific inflammatory potential biomarker levels may differentiate pulpal disease states. Integrating molecular diagnostics into longitudinal clinical trials and eventually into routine endodontic practice, could revolutionise treatment decisions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 1","pages":"23-37"},"PeriodicalIF":7.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bandana Rana, Sanjiv Neupane, Yam Prasad Aryal, Elina Pokharel, Tae-Young Kim, Jae-Hee Lee, Je-Hee Jang, Hitoshi Yamamoto, Ji-Youn Kim, Seo-Young An, Chang-Hyeon An, Jae-Kwang Jung, Wern-Joo Sohn, Sung-Jin Cho, Jung-Hong Ha, Jae-Young Kim
Aim
Prickle planar cell polarity (PCP) protein 2 (Prickle2) encodes a homologue of Drosophila prickle and is involved in the non-canonical Wnt/PCP signalling pathway. However, its exact role in dentinogenesis remains unclear. Dentinogenesis, a key process in tooth morphogenesis, involves the patterned arrangement of odontoblasts and the formation of dentine matrix along the pulp cavity. This study investigates the role of PCP signalling, particularly Prickle2, in odontogenesis and dentine formation. Additionally, this study evaluates the potential application of Prickle2 modulation for dentine regeneration using an animal experimental model.
Methodology
The developmental function of Prickle2 in tooth morphogenesis was examined by analysing its precise expression pattern in the primary enamel knot. Gain and loss of function studies were performed using in vitro organ cultivation and renal capsule transplantation. At embryonic day 13 (E13), Prickle2 was knocked down using small interfering ribonucleic acid (siRNA) treatment, and histogenesis, cellular physiology (proliferation and apoptosis), and the expression of PCP pathway-related genes and tooth-related signalling molecules were examined. Furthermore, renal capsule transplantation was conducted for 3 weeks to analyse the morphological changes in tooth crown formation. To evaluate the clinical applicability of Prickle2 modulation in dentine regeneration, a pulp exposure animal model was employed, locally administering siRNA against Prickle2 into the exposed pulp cavity of the maxillary first molar at week 8 for 6 weeks.
Results
At E13.5, in situ hybridization revealed the distinctive expression of Prickle2 in the enamel knot area. Knockdown of Prickle2 at E13 led to significant alterations in histogenesis and changes in key signalling molecule expression. Renal capsule transplantation resulted in morphological changes, including a thicker pre-dentine layer and the formation of a more opaque crown. In the pulp exposure model, siRNA treatment facilitated the formation of a dentinal bridge compared to controls.
Conclusion
Our findings suggest that Prickle2 regulates dentinogenesis through Wnt/PCP signalling. Modulating Prickle2 expression presents a promising approach for dentine regeneration.
{"title":"Modulation of Prickle2 Expression to Facilitate Dentine Formation: A Laboratory Investigation","authors":"Bandana Rana, Sanjiv Neupane, Yam Prasad Aryal, Elina Pokharel, Tae-Young Kim, Jae-Hee Lee, Je-Hee Jang, Hitoshi Yamamoto, Ji-Youn Kim, Seo-Young An, Chang-Hyeon An, Jae-Kwang Jung, Wern-Joo Sohn, Sung-Jin Cho, Jung-Hong Ha, Jae-Young Kim","doi":"10.1111/iej.70024","DOIUrl":"10.1111/iej.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Prickle planar cell polarity (PCP) protein 2 (Prickle2) encodes a homologue of <i>Drosophila</i> prickle and is involved in the non-canonical Wnt/PCP signalling pathway. However, its exact role in dentinogenesis remains unclear. Dentinogenesis, a key process in tooth morphogenesis, involves the patterned arrangement of odontoblasts and the formation of dentine matrix along the pulp cavity. This study investigates the role of PCP signalling, particularly Prickle2, in odontogenesis and dentine formation. Additionally, this study evaluates the potential application of Prickle2 modulation for dentine regeneration using an animal experimental model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>The developmental function of Prickle2 in tooth morphogenesis was examined by analysing its precise expression pattern in the primary enamel knot. Gain and loss of function studies were performed using in vitro organ cultivation and renal capsule transplantation. At embryonic day 13 (E13), Prickle2 was knocked down using small interfering ribonucleic acid (siRNA) treatment, and histogenesis, cellular physiology (proliferation and apoptosis), and the expression of PCP pathway-related genes and tooth-related signalling molecules were examined. Furthermore, renal capsule transplantation was conducted for 3 weeks to analyse the morphological changes in tooth crown formation. To evaluate the clinical applicability of Prickle2 modulation in dentine regeneration, a pulp exposure animal model was employed, locally administering siRNA against Prickle2 into the exposed pulp cavity of the maxillary first molar at week 8 for 6 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At E13.5, in situ hybridization revealed the distinctive expression of Prickle2 in the enamel knot area. Knockdown of Prickle2 at E13 led to significant alterations in histogenesis and changes in key signalling molecule expression. Renal capsule transplantation resulted in morphological changes, including a thicker pre-dentine layer and the formation of a more opaque crown. In the pulp exposure model, siRNA treatment facilitated the formation of a dentinal bridge compared to controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that Prickle2 regulates dentinogenesis through Wnt/PCP signalling. Modulating Prickle2 expression presents a promising approach for dentine regeneration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"58 12","pages":"1902-1912"},"PeriodicalIF":7.1,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015145","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}
This article aims to introduce and elaborate on the innovative concept of Functional Endodontic Volume (FEV), a biologically driven approach to root canal shaping. This concept emphasizes the importance of volumetric preparation aimed at enhancing irrigation dynamics during root canal treatment, all while maintaining the tooth's structural integrity.
Summary
In recent years, contemporary endodontics has progressively shifted towards methods that prioritize irrigation-based disinfection. Traditional philosophies surrounding canal preparation have predominantly revolved around standardized apical sizes and tapers, often failing to address the true objectives of modern root canal treatment. This article advocates for the FEV concept—a sophisticated and tailored shaping strategy focused on optimizing the efficacy of irrigants used in treatment, promoting mechanical safety, and conserving the structural framework of the tooth. The FEV approach moves beyond merely considering the diameter or taper of the canal; instead, it emphasizes a comprehensive three-dimensional shaping method that is particularly beneficial in anatomically complex root canal systems. By prioritizing the effective exchange of irrigants and the delivery of energy throughout the entire canal volume, this concept not only enhances disinfection but also minimizes the risk of procedural complications. The implications of adopting the FEV concept extend to the clinical and research realms. It can guide the development and refinement of new shaping protocols, the design of endodontic instruments, and the establishment of standardized reporting metrics in endodontic studies. This holistic approach has the potential to revolutionize the way endodontic procedures are performed and assessed.
Conclusion
The FEV approach redefines the objectives of canal shaping by concentrating on achieving an effective disinfection-driven canal volume rather than adherence to fixed apical dimensions. It supports a minimally invasive technique that ensures optimal irrigant exchange and agitation, thereby enhancing overall treatment outcomes. The FEV concept could serve as a valuable clinical and research framework, enabling practitioners and researchers to evaluate and compare various shaping systems with a focus on volumetric efficacy.
{"title":"Redefining Root Canal Shaping: From Size to Volume—The Functional Endodontic Volume Concept","authors":"Mohammed Turky, Ove A. Peters","doi":"10.1111/iej.70029","DOIUrl":"10.1111/iej.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This article aims to introduce and elaborate on the innovative concept of <i>Functional Endodontic Volume</i> (FEV), a biologically driven approach to root canal shaping. This concept emphasizes the importance of volumetric preparation aimed at enhancing irrigation dynamics during root canal treatment, all while maintaining the tooth's structural integrity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Summary</h3>\u0000 \u0000 <p>In recent years, contemporary endodontics has progressively shifted towards methods that prioritize irrigation-based disinfection. Traditional philosophies surrounding canal preparation have predominantly revolved around standardized apical sizes and tapers, often failing to address the true objectives of modern root canal treatment. This article advocates for the FEV concept—a sophisticated and tailored shaping strategy focused on optimizing the efficacy of irrigants used in treatment, promoting mechanical safety, and conserving the structural framework of the tooth. The FEV approach moves beyond merely considering the diameter or taper of the canal; instead, it emphasizes a comprehensive three-dimensional shaping method that is particularly beneficial in anatomically complex root canal systems. By prioritizing the effective exchange of irrigants and the delivery of energy throughout the entire canal volume, this concept not only enhances disinfection but also minimizes the risk of procedural complications. The implications of adopting the FEV concept extend to the clinical and research realms. It can guide the development and refinement of new shaping protocols, the design of endodontic instruments, and the establishment of standardized reporting metrics in endodontic studies. This holistic approach has the potential to revolutionize the way endodontic procedures are performed and assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The FEV approach redefines the objectives of canal shaping by concentrating on achieving an effective disinfection-driven canal volume rather than adherence to fixed apical dimensions. It supports a minimally invasive technique that ensures optimal irrigant exchange and agitation, thereby enhancing overall treatment outcomes. The FEV concept could serve as a valuable clinical and research framework, enabling practitioners and researchers to evaluate and compare various shaping systems with a focus on volumetric efficacy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"58 12","pages":"1810-1813"},"PeriodicalIF":7.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000416","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}
<div> <section> <h3> Aim</h3> <p>This study explores how lipid metabolic reprogramming contributes to the pathogenesis of pulpitis and identifies key molecular targets involved in regulating inflammation, with the goal of developing metabolic interventions to preserve dental pulp vitality.</p> </section> <section> <h3> Methodology</h3> <p>Primary human dental pulp cells (HDPCs) were stimulated with lipopolysaccharide (LPS) and subjected to integrated transcriptomic and metabolomic profiling to map inflammation-associated metabolic shifts. Functional validation included linolenic acid (LA) supplementation (alone or combined with a Fatty Acid Synthase (FASN) inhibitor, TVB-2640), Nuclear receptor subfamily 4 group A member 1 (NR4A1) knockdown, cytokine/NF-κB assessment (ELISA, Western blot), and lipid droplet/FASN visualisation (immunofluorescence). FASN expression was confirmed in vivo (rat pulpitis model). Key findings were verified in clinical pulpitis samples (histology, immunofluorescence, targeted fatty acid profiling).</p> </section> <section> <h3> Results</h3> <p>LPS stimulation significantly upregulated FASN expression and induced lipid accumulation in HDPCs and rat pulpitis models (<i>p</i> < 0.001). Transcriptomic analysis revealed marked downregulation of NR4A1, while metabolomic profiling showed depletion of key anti-inflammatory/pro-resolving PUFA precursors, including LA and γ-linolenic acid (GLA). Integrated transcriptomic–metabolomic analysis identified LA as a metabolite with high centrality in the lipid metabolic network, and NR4A1 as a significantly downregulated transcription factor linked to multiple lipid-related pathways. LA supplementation suppressed pro-inflammatory cytokines (IL-1β, TNF-α, phosphorylated NF-κB p65) and restored NR4A1 expression (<i>p</i> < 0.05). Combining LA with the FASN inhibitor TVB-2640 synergistically enhanced NR4A1 restoration and anti-inflammatory effects (<i>p</i> < 0.001). siRNA-mediated NR4A1 knockdown abolished the benefits of LA. In human pulpitis tissues, FASN upregulation, NR4A1 downregulation, and elevated palmitic acid were observed (<i>p</i> < 0.001), along with increased levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).</p> </section> <section> <h3> Conclusions</h3> <p>This study reveals a pathological FASN–LA–NR4A1 regulatory axis linking lipid metabolism to inflammatory amplification in pulpitis. Dual targeting of fatty acid synthesis and lipid depletion—through FASN inhibition and LA supplementation—attenuates inflammation via NR4A1-dependent mechanisms. These findings lay the groundwork for metabolic approaches to modulate inflammation
目的：本研究旨在探讨脂质代谢重编程在牙髓炎发病机制中的作用，并确定参与炎症调节的关键分子靶点，以开发代谢干预措施以保持牙髓活力。方法：用脂多糖（LPS）刺激原代人牙髓细胞（HDPCs），并进行综合转录组学和代谢组学分析，以绘制炎症相关的代谢变化。功能验证包括亚麻酸（LA）补充（单独或联合脂肪酸合成酶（FASN）抑制剂TVB-2640），核受体亚家族4组a成员1 （NR4A1）敲低，细胞因子/NF-κB评估（ELISA, Western blot）和脂滴/FASN可视化（免疫荧光）。体内（大鼠牙髓炎模型）证实FASN表达。在临床牙髓炎样本中验证了主要发现（组织学、免疫荧光、靶向脂肪酸谱）。结果：LPS刺激显著上调HDPCs和大鼠牙髓炎模型中FASN的表达并诱导脂质积累(p)。结论：本研究揭示了病理性FASN- la - nr4a1调节轴将牙髓炎中的脂质代谢与炎症扩增联系起来。脂肪酸合成和脂质消耗的双重靶向-通过FASN抑制和LA补充-通过nr4a1依赖机制减轻炎症。这些发现为代谢方法调节牙髓学炎症奠定了基础。
{"title":"Laboratory Investigation of Lipid Metabolic Reprogramming in Pulpitis: The Linolenic Acid–FASN–NR4A1 Axis in Modulating Dental Pulp Inflammation","authors":"Mengqi Zhou, Xin Sui, Changyi Li, Qiangqiang Zhou, Xiaoling Wei, Huaxing Xu","doi":"10.1111/iej.70026","DOIUrl":"10.1111/iej.70026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study explores how lipid metabolic reprogramming contributes to the pathogenesis of pulpitis and identifies key molecular targets involved in regulating inflammation, with the goal of developing metabolic interventions to preserve dental pulp vitality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Primary human dental pulp cells (HDPCs) were stimulated with lipopolysaccharide (LPS) and subjected to integrated transcriptomic and metabolomic profiling to map inflammation-associated metabolic shifts. Functional validation included linolenic acid (LA) supplementation (alone or combined with a Fatty Acid Synthase (FASN) inhibitor, TVB-2640), Nuclear receptor subfamily 4 group A member 1 (NR4A1) knockdown, cytokine/NF-κB assessment (ELISA, Western blot), and lipid droplet/FASN visualisation (immunofluorescence). FASN expression was confirmed in vivo (rat pulpitis model). Key findings were verified in clinical pulpitis samples (histology, immunofluorescence, targeted fatty acid profiling).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LPS stimulation significantly upregulated FASN expression and induced lipid accumulation in HDPCs and rat pulpitis models (<i>p</i> < 0.001). Transcriptomic analysis revealed marked downregulation of NR4A1, while metabolomic profiling showed depletion of key anti-inflammatory/pro-resolving PUFA precursors, including LA and γ-linolenic acid (GLA). Integrated transcriptomic–metabolomic analysis identified LA as a metabolite with high centrality in the lipid metabolic network, and NR4A1 as a significantly downregulated transcription factor linked to multiple lipid-related pathways. LA supplementation suppressed pro-inflammatory cytokines (IL-1β, TNF-α, phosphorylated NF-κB p65) and restored NR4A1 expression (<i>p</i> < 0.05). Combining LA with the FASN inhibitor TVB-2640 synergistically enhanced NR4A1 restoration and anti-inflammatory effects (<i>p</i> < 0.001). siRNA-mediated NR4A1 knockdown abolished the benefits of LA. In human pulpitis tissues, FASN upregulation, NR4A1 downregulation, and elevated palmitic acid were observed (<i>p</i> < 0.001), along with increased levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study reveals a pathological FASN–LA–NR4A1 regulatory axis linking lipid metabolism to inflammatory amplification in pulpitis. Dual targeting of fatty acid synthesis and lipid depletion—through FASN inhibition and LA supplementation—attenuates inflammation via NR4A1-dependent mechanisms. These findings lay the groundwork for metabolic approaches to modulate inflammation","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"58 12","pages":"1913-1925"},"PeriodicalIF":7.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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