Yuan-Hao Wen, Yu-Xiu Lin, Lu Zhou, Chen Lin, Lu Zhang
Apical periodontitis (AP) is featured by a persistent inflammatory response and alveolar bone resorption initiated by microorganisms, posing risks to both dental and systemic health. Nonsurgical endodontic treatment is the recommended treatment plan for AP with a high success rate, but in some cases, periapical lesions may persist despite standard endodontic treatment. Better comprehension of the AP inflammatory microenvironment can help develop adjunct therapies to improve the outcome of endodontic treatment. This review presents an overview of the immune landscape in AP, elucidating how microbial invasion triggers host immune activation and shapes the inflammatory microenvironment, ultimately impacting bone homeostasis. The destructive effect of excessive immune activation on periapical tissues is emphasized. This review aimed to systematically discuss the immunological basis of AP, the inflammatory bone resorption and the immune cell network in AP, thereby providing insights into potential immunotherapeutic strategies such as targeted therapy, antioxidant therapy, adoptive cell therapy and cytokine therapy to mitigate AP-associated tissue destruction.
根尖周炎（Apical periodontitis，AP）的特征是由微生物引发的持续性炎症反应和牙槽骨吸收，对牙齿和全身健康都构成威胁。非手术牙髓治疗是牙髓炎的推荐治疗方案，成功率很高，但在某些情况下，尽管进行了标准的牙髓治疗，根尖周病变仍可能持续存在。更好地了解 AP 炎症微环境有助于开发辅助疗法，改善牙髓治疗的效果。本综述概述了 AP 的免疫状况，阐明了微生物入侵如何引发宿主免疫激活并塑造炎症微环境，最终影响骨稳态。文章强调了过度免疫激活对根尖周组织的破坏性影响。本综述旨在系统地讨论 AP 的免疫学基础、炎性骨吸收和 AP 中的免疫细胞网络，从而为潜在的免疫治疗策略（如靶向治疗、抗氧化治疗、收养细胞治疗和细胞因子治疗）提供见解，以减轻 AP 相关的组织破坏。
{"title":"The immune landscape in apical periodontitis: From mechanism to therapy","authors":"Yuan-Hao Wen, Yu-Xiu Lin, Lu Zhou, Chen Lin, Lu Zhang","doi":"10.1111/iej.14125","DOIUrl":"10.1111/iej.14125","url":null,"abstract":"<p>Apical periodontitis (AP) is featured by a persistent inflammatory response and alveolar bone resorption initiated by microorganisms, posing risks to both dental and systemic health. Nonsurgical endodontic treatment is the recommended treatment plan for AP with a high success rate, but in some cases, periapical lesions may persist despite standard endodontic treatment. Better comprehension of the AP inflammatory microenvironment can help develop adjunct therapies to improve the outcome of endodontic treatment. This review presents an overview of the immune landscape in AP, elucidating how microbial invasion triggers host immune activation and shapes the inflammatory microenvironment, ultimately impacting bone homeostasis. The destructive effect of excessive immune activation on periapical tissues is emphasized. This review aimed to systematically discuss the immunological basis of AP, the inflammatory bone resorption and the immune cell network in AP, thereby providing insights into potential immunotherapeutic strategies such as targeted therapy, antioxidant therapy, adoptive cell therapy and cytokine therapy to mitigate AP-associated tissue destruction.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 11","pages":"1526-1545"},"PeriodicalIF":5.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.14125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859669","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}
Zuodong Zhao, Catia Attanasio, Chen Zong, Mariano Simón Pedano, María Cadenas de Llano-Pérula
Objectives
The objective of this study is to analyse the gene expression profile of the dental pulp (DP) of human premolars subjected to 7 and 28 days of orthodontic force (OF) in vivo by using RNA sequencing. The maxillary and mandibular DP were additionally compared.
Methods
Healthy patients requiring orthodontic premolar extractions were randomly assigned to one of the three groups: control (CG) where no OF was applied, 7 and 28 days, where premolars were extracted either 7 or 28 days after the application of a 50–100 g OF. Total RNA was extracted from the DP and analysed via RNA-seq. Differentially expressed genes (DEGs) were identified using a false discovery rate and fold change threshold of <0.05 and ≥1.5, respectively. Functional analysis was performed.
Results
After 7 days of OF, pulp reaction indicates immune response, hypoxia, DNA damage and epigenetic regulation. After 28 days, cell adhesion, migration, organization and tissue repair are evident. The maxillary and mandibular pulp tissues react differently to OF. The maxilla exhibits minimal alterations, mostly related to immune response at 7 days and tissue repair at 28 days, whereas the mandible shows mostly DNA damage and epigenetic regulation at 7 days and return to the original state at 28 days.
Conclusions
This study demonstrates that the early reaction of the DP to OF is marked by immune response, hypoxia and DNA damage. In contrast, after 28 days, cell adhesion, migration, organization, tissue repair and dentine formation are observed. Maxillary and mandibular premolars react differently to OF: although the maxilla exhibits minimal alterations at both time points, the mandible mostly shows DNA damage, epigenetic regulation, and immune response at 7 days. These disparities could stem from different blood supplies or the lower maxillary bone density, potentially triggering faster biological changes. Our findings provide insights into the gene regulatory networks modulating DP response to OF.
研究目的本研究的目的是利用 RNA 测序技术分析人体前臼齿在受到 7 天和 28 天正畸力（OF）作用时牙髓（DP）的基因表达谱。方法：将需要正畸拔除前臼齿的健康患者随机分配到三组中的一组：未施加正畸力的对照组（CG）、施加 50-100 克正畸力 7 天和 28 天后拔除前臼齿的对照组（CG）、施加 50-100 克正畸力 7 天和 28 天后拔除前臼齿的对照组（CG）和施加 50-100 克正畸力 28 天后拔除前臼齿的对照组（CG）。从DP中提取总RNA，并通过RNA-seq进行分析。使用假发现率和折叠变化阈值确定差异表达基因（DEGs）：经过 7 天的 OF 后，纸浆反应显示了免疫反应、缺氧、DNA 损伤和表观遗传调控。28 天后，细胞粘附、迁移、组织和组织修复明显。上颌和下颌牙髓组织对 OF 的反应不同。上颌骨的变化极小，7天时主要与免疫反应有关，28天时与组织修复有关，而下颌骨主要表现为7天时的DNA损伤和表观遗传调节，28天时恢复原状：本研究表明，DP 对 OF 的早期反应主要表现为免疫反应、缺氧和 DNA 损伤。相反，28 天后，观察到细胞粘附、迁移、组织、组织修复和牙本质形成。上颌和下颌前磨牙对 OF 的反应不同：虽然上颌在两个时间点的变化都很小，但下颌在 7 天时主要表现为 DNA 损伤、表观遗传调节和免疫反应。这些差异可能源于不同的血液供应或较低的上颌骨密度，从而可能引发更快的生物变化。我们的研究结果让我们对调节 DP 对 OF 的反应的基因调控网络有了更深入的了解。
{"title":"How does orthodontic tooth movement influence the dental pulp? RNA-sequencing on human premolars","authors":"Zuodong Zhao, Catia Attanasio, Chen Zong, Mariano Simón Pedano, María Cadenas de Llano-Pérula","doi":"10.1111/iej.14131","DOIUrl":"10.1111/iej.14131","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The objective of this study is to analyse the gene expression profile of the dental pulp (DP) of human premolars subjected to 7 and 28 days of orthodontic force (OF) <i>in vivo</i> by using RNA sequencing. The maxillary and mandibular DP were additionally compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Healthy patients requiring orthodontic premolar extractions were randomly assigned to one of the three groups: control (CG) where no OF was applied, 7 and 28 days, where premolars were extracted either 7 or 28 days after the application of a 50–100 g OF. Total RNA was extracted from the DP and analysed via RNA-seq. Differentially expressed genes (DEGs) were identified using a false discovery rate and fold change threshold of <0.05 and ≥1.5, respectively. Functional analysis was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After 7 days of OF, pulp reaction indicates immune response, hypoxia, DNA damage and epigenetic regulation. After 28 days, cell adhesion, migration, organization and tissue repair are evident. The maxillary and mandibular pulp tissues react differently to OF. The maxilla exhibits minimal alterations, mostly related to immune response at 7 days and tissue repair at 28 days, whereas the mandible shows mostly DNA damage and epigenetic regulation at 7 days and return to the original state at 28 days.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates that the early reaction of the DP to OF is marked by immune response, hypoxia and DNA damage. In contrast, after 28 days, cell adhesion, migration, organization, tissue repair and dentine formation are observed. Maxillary and mandibular premolars react differently to OF: although the maxilla exhibits minimal alterations at both time points, the mandible mostly shows DNA damage, epigenetic regulation, and immune response at 7 days. These disparities could stem from different blood supplies or the lower maxillary bone density, potentially triggering faster biological changes. Our findings provide insights into the gene regulatory networks modulating DP response to OF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 12","pages":"1783-1801"},"PeriodicalIF":5.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859668","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}
Ting Yang, Peiqi Liu, Zixin Qiu, Yuejiao Zhang, Shaofeng An
Aim
The purpose of this study was to investigate the role of calcium-sensing receptor (CaSR) in the angiogenic differentiation of lipopolysaccharide (LPS)-treated human dental pulp cells (hDPCs).
Methodology
The LPS-induced hDPCs were cultured in the medium with different combinations of CaSR agonist R568 and antagonist Calhex231. The cell proliferation, migration, and angiogenic capacity were measured by Cell Counting Kit-8 (CCK-8), scratch wound healing, and tube formation assays, respectively. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were conducted to determine the gene/protein expression of CaSR, inflammatory mediators, and angiogenic-associated markers. The activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) was assessed by western blot analysis.
Results
The cell proliferation was elevated in response to R568 or Calhex231 exposure, but an enhanced cell migration was only found in cultures supplemented with Calhex231. Furthermore, R568 was found to potentiate the formation of vessel-like structure, up-regulated the protein expression of tumour necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and stromal cell-derived factor (SDF)-1; comparable influences were also observed in R568-stimulated cells in the presence of PI3K inhibitor LY294002. In contrast, Calhex231 obviously inhibited the tube formation and VEGF protein level, whereas promoted the production of IL-6, TNF-α, and eNOS; however, in the presence of LY294002, Calhex231 showed a significant promotion on the protein expression of CaSR, VEGF, and SDF-1. In addition, R568 exhibited a promotive action on the Akt phosphorylation, which can be reversed by LY294002.
Conclusions
Our results demonstrated that CaSR can regulate the angiogenic differentiation of LPS-treated hDPCs with an involvement of the PI3K/Akt signalling pathway.
{"title":"Calcium-sensing receptor regulates the angiogenic differentiation of LPS-treated human dental pulp cells via the phosphoinositide 3-kinase/Akt pathway in vitro","authors":"Ting Yang, Peiqi Liu, Zixin Qiu, Yuejiao Zhang, Shaofeng An","doi":"10.1111/iej.14129","DOIUrl":"10.1111/iej.14129","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The purpose of this study was to investigate the role of calcium-sensing receptor (CaSR) in the angiogenic differentiation of lipopolysaccharide (LPS)-treated human dental pulp cells (hDPCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>The LPS-induced hDPCs were cultured in the medium with different combinations of CaSR agonist R568 and antagonist Calhex231. The cell proliferation, migration, and angiogenic capacity were measured by Cell Counting Kit-8 (CCK-8), scratch wound healing, and tube formation assays, respectively. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and western blot were conducted to determine the gene/protein expression of CaSR, inflammatory mediators, and angiogenic-associated markers. The activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) was assessed by western blot analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The cell proliferation was elevated in response to R568 or Calhex231 exposure, but an enhanced cell migration was only found in cultures supplemented with Calhex231. Furthermore, R568 was found to potentiate the formation of vessel-like structure, up-regulated the protein expression of tumour necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and stromal cell-derived factor (SDF)-1; comparable influences were also observed in R568-stimulated cells in the presence of PI3K inhibitor LY294002. In contrast, Calhex231 obviously inhibited the tube formation and VEGF protein level, whereas promoted the production of IL-6, TNF-α, and eNOS; however, in the presence of LY294002, Calhex231 showed a significant promotion on the protein expression of CaSR, VEGF, and SDF-1. In addition, R568 exhibited a promotive action on the Akt phosphorylation, which can be reversed by LY294002.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results demonstrated that CaSR can regulate the angiogenic differentiation of LPS-treated hDPCs with an involvement of the PI3K/Akt signalling pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 11","pages":"1655-1668"},"PeriodicalIF":5.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855391","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}
Bianca Araújo Magalhães Damiani, Karem Paula Pinto, Cláudio Malizia Alves Ferreira, Estéfano Borgo Sarmento, Carolina Oliveira de Lima, Caroline Silva Cassimiro, Luciana Moura Sassone, Emmanuel João Nogueira Leal da Silva
Aim
The present study investigated the influence of apical periodontitis (AP) on the severity of rheumatoid arthritis (RA) using a Wistar rat model.
Methodology
Forty male Wistar rats were distributed across four groups (n = 10) based on the induction of RA and AP: Control, RA, AP, and RA + AP. RA was induced through two immunisations with type II collagen emulsified in incomplete Freund's adjuvant, followed by one immunisation with complete Freund's adjuvant. After 21 days of RA induction, AP was induced by exposing the pulp of four molars. Animals were euthanized after 28 days of pulp exposure. Through the experiment, visual and behavioural assessments tracked RA development and the knees and hind paw joints were measured. Micro-computed tomography scans of knees and hind paws, as well as mandibles and maxillae, were conducted to evaluate RA severity and the presence of AP, respectively. Serum samples were collected to analyse proinflammatory cytokines (IL-1β, IL-2, IL-17, and TNF-α). Non-parametric data were analysed using the Kruskal-Wallis test followed by Student–Newman–Keuls test, while one-way anova followed by Tukey's test was performed for parametric data. A significance level of 5% was employed.
Results
All molars submitted to access cavity developed AP. All joints subjected to arthritis induction developed the disease, with AP + RA demonstrating a higher arthritis severity when compared to the RA group (p < .05). RA + AP group displayed a significantly larger hind paw and knee circumference compared to the RA group (p < .05). Micro-CT images of RA and RA + AP groups revealed joints with erosions and bone deformities, with a significantly lower bone surface density, lower trabecular number and higher trabecular separation in the hind paw and a significantly lower percent bone volume and higher trabecular separation in the knees of RA + AP group compared to RA group (p < .05). RA + AP group exhibited a significantly higher level of TNF-α and a lower level of IL-2 compared to all other groups (p < .05). Both RA and RA + AP groups had significantly higher IL-17 levels (p < .05), while there was no significant difference in IL-1β levels among the groups (p > .05).
Conclusion
The findings from this study underscore a possible relationship between apical periodontitis and the exacerbation of rheumatoid arthritis.
目的：本研究以Wistar大鼠为模型，研究根尖牙周炎（AP）对类风湿性关节炎（RA）严重程度的影响：根据 RA 和 AP 的诱导情况，将 40 只雄性 Wistar 大鼠分为四组（n = 10）：对照组、RA 组、AP 组和 RA + AP 组。先用不完全弗氏佐剂乳化的 II 型胶原蛋白进行两次免疫诱导 RA，再用完全弗氏佐剂进行一次免疫诱导。诱导 RA 21 天后，暴露四颗臼齿的牙髓诱导 AP。暴露牙髓 28 天后，动物被安乐死。在整个实验过程中，通过视觉和行为评估跟踪 RA 的发展，并测量膝关节和后爪关节。对膝盖和后爪以及下颌骨和上颌骨进行微型计算机断层扫描，分别评估RA的严重程度和AP的存在情况。采集血清样本分析促炎细胞因子（IL-1β、IL-2、IL-17 和 TNF-α）。非参数数据采用 Kruskal-Wallis 检验和 Student-Newman-Keuls 检验进行分析，参数数据则采用单因素分析和 Tukey's 检验进行分析。显著性水平为 5%：结果：所有进入龋洞的磨牙均出现 AP。与 RA 组相比，AP + RA 组的关节炎严重程度更高（P .05）：本研究的结论强调了根尖牙周炎与类风湿性关节炎恶化之间可能存在的关系。
{"title":"Apical periodontitis as an aggravating factor for the severity of rheumatoid arthritis: An animal study","authors":"Bianca Araújo Magalhães Damiani, Karem Paula Pinto, Cláudio Malizia Alves Ferreira, Estéfano Borgo Sarmento, Carolina Oliveira de Lima, Caroline Silva Cassimiro, Luciana Moura Sassone, Emmanuel João Nogueira Leal da Silva","doi":"10.1111/iej.14130","DOIUrl":"10.1111/iej.14130","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The present study investigated the influence of apical periodontitis (AP) on the severity of rheumatoid arthritis (RA) using a Wistar rat model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Forty male Wistar rats were distributed across four groups (<i>n</i> = 10) based on the induction of RA and AP: Control, RA, AP, and RA + AP. RA was induced through two immunisations with type II collagen emulsified in incomplete Freund's adjuvant, followed by one immunisation with complete Freund's adjuvant. After 21 days of RA induction, AP was induced by exposing the pulp of four molars. Animals were euthanized after 28 days of pulp exposure. Through the experiment, visual and behavioural assessments tracked RA development and the knees and hind paw joints were measured. Micro-computed tomography scans of knees and hind paws, as well as mandibles and maxillae, were conducted to evaluate RA severity and the presence of AP, respectively. Serum samples were collected to analyse proinflammatory cytokines (IL-1β, IL-2, IL-17, and TNF-α). Non-parametric data were analysed using the Kruskal-Wallis test followed by Student–Newman–Keuls test, while one-way <span>anova</span> followed by Tukey's test was performed for parametric data. A significance level of 5% was employed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All molars submitted to access cavity developed AP. All joints subjected to arthritis induction developed the disease, with AP + RA demonstrating a higher arthritis severity when compared to the RA group (<i>p</i> < .05). RA + AP group displayed a significantly larger hind paw and knee circumference compared to the RA group (<i>p</i> < .05). Micro-CT images of RA and RA + AP groups revealed joints with erosions and bone deformities, with a significantly lower bone surface density, lower trabecular number and higher trabecular separation in the hind paw and a significantly lower percent bone volume and higher trabecular separation in the knees of RA + AP group compared to RA group (<i>p</i> < .05). RA + AP group exhibited a significantly higher level of TNF-α and a lower level of IL-2 compared to all other groups (<i>p</i> < .05). Both RA and RA + AP groups had significantly higher IL-17 levels (<i>p</i> < .05), while there was no significant difference in IL-1β levels among the groups (<i>p</i> > .05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings from this study underscore a possible relationship between apical periodontitis and the exacerbation of rheumatoid arthritis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 11","pages":"1669-1681"},"PeriodicalIF":5.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855390","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}
Hossein Mohammad-Rahimi, Fatemeh Sohrabniya, Seyed AmirHossein Ourang, Omid Dianat, Anita Aminoshariae, Venkateshbabu Nagendrababu, Paul Michael Howell Dummer, Henry F. Duncan, Ali Nosrat
Artificial intelligence (AI) is emerging as a transformative technology in healthcare, including endodontics. A gap in knowledge exists in understanding AI's applications and limitations among endodontic experts. This comprehensive review aims to (A) elaborate on technical and ethical aspects of using data to implement AI models in endodontics; (B) elaborate on evaluation metrics; (C) review the current applications of AI in endodontics; and (D) review the limitations and barriers to real-world implementation of AI in the field of endodontics and its future potentials/directions. The article shows that AI techniques have been applied in endodontics for critical tasks such as detection of radiolucent lesions, analysis of root canal morphology, prediction of treatment outcome and post-operative pain and more. Deep learning models like convolutional neural networks demonstrate high accuracy in these applications. However, challenges remain regarding model interpretability, generalizability, and adoption into clinical practice. When thoughtfully implemented, AI has great potential to aid with diagnostics, treatment planning, clinical interventions, and education in the field of endodontics. However, concerted efforts are still needed to address limitations and to facilitate integration into clinical workflows.
{"title":"Artificial intelligence in endodontics: Data preparation, clinical applications, ethical considerations, limitations, and future directions","authors":"Hossein Mohammad-Rahimi, Fatemeh Sohrabniya, Seyed AmirHossein Ourang, Omid Dianat, Anita Aminoshariae, Venkateshbabu Nagendrababu, Paul Michael Howell Dummer, Henry F. Duncan, Ali Nosrat","doi":"10.1111/iej.14128","DOIUrl":"10.1111/iej.14128","url":null,"abstract":"<p>Artificial intelligence (AI) is emerging as a transformative technology in healthcare, including endodontics. A gap in knowledge exists in understanding AI's applications and limitations among endodontic experts. This comprehensive review aims to (A) elaborate on technical and ethical aspects of using data to implement AI models in endodontics; (B) elaborate on evaluation metrics; (C) review the current applications of AI in endodontics; and (D) review the limitations and barriers to real-world implementation of AI in the field of endodontics and its future potentials/directions. The article shows that AI techniques have been applied in endodontics for critical tasks such as detection of radiolucent lesions, analysis of root canal morphology, prediction of treatment outcome and post-operative pain and more. Deep learning models like convolutional neural networks demonstrate high accuracy in these applications. However, challenges remain regarding model interpretability, generalizability, and adoption into clinical practice. When thoughtfully implemented, AI has great potential to aid with diagnostics, treatment planning, clinical interventions, and education in the field of endodontics. However, concerted efforts are still needed to address limitations and to facilitate integration into clinical workflows.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 11","pages":"1566-1595"},"PeriodicalIF":5.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.14128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792395","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}
Seyed AmirHossein Ourang, Fatemeh Sohrabniya, Hossein Mohammad-Rahimi, Omid Dianat, Anita Aminoshariae, Venkateshbabu Nagendrababu, Paul Michael Howell Dummer, Henry F. Duncan, Ali Nosrat
The integration of artificial intelligence (AI) in healthcare has seen significant advancements, particularly in areas requiring image interpretation. Endodontics, a specialty within dentistry, stands to benefit immensely from AI applications, especially in interpreting radiographic images. However, there is a knowledge gap among endodontists regarding the fundamentals of machine learning and deep learning, hindering the full utilization of AI in this field. This narrative review aims to: (A) elaborate on the basic principles of machine learning and deep learning and present the basics of neural network architectures; (B) explain the workflow for developing AI solutions, from data collection through clinical integration; (C) discuss specific AI tasks and applications relevant to endodontic diagnosis and treatment. The article shows that AI offers diverse practical applications in endodontics. Computer vision methods help analyse images while natural language processing extracts insights from text. With robust validation, these techniques can enhance diagnosis, treatment planning, education, and patient care. In conclusion, AI holds significant potential to benefit endodontic research, practice, and education. Successful integration requires an evolving partnership between clinicians, computer scientists, and industry.
{"title":"Artificial intelligence in endodontics: Fundamental principles, workflow, and tasks","authors":"Seyed AmirHossein Ourang, Fatemeh Sohrabniya, Hossein Mohammad-Rahimi, Omid Dianat, Anita Aminoshariae, Venkateshbabu Nagendrababu, Paul Michael Howell Dummer, Henry F. Duncan, Ali Nosrat","doi":"10.1111/iej.14127","DOIUrl":"10.1111/iej.14127","url":null,"abstract":"<p>The integration of artificial intelligence (AI) in healthcare has seen significant advancements, particularly in areas requiring image interpretation. Endodontics, a specialty within dentistry, stands to benefit immensely from AI applications, especially in interpreting radiographic images. However, there is a knowledge gap among endodontists regarding the fundamentals of machine learning and deep learning, hindering the full utilization of AI in this field. This narrative review aims to: (A) elaborate on the basic principles of machine learning and deep learning and present the basics of neural network architectures; (B) explain the workflow for developing AI solutions, from data collection through clinical integration; (C) discuss specific AI tasks and applications relevant to endodontic diagnosis and treatment. The article shows that AI offers diverse practical applications in endodontics. Computer vision methods help analyse images while natural language processing extracts insights from text. With robust validation, these techniques can enhance diagnosis, treatment planning, education, and patient care. In conclusion, AI holds significant potential to benefit endodontic research, practice, and education. Successful integration requires an evolving partnership between clinicians, computer scientists, and industry.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 11","pages":"1546-1565"},"PeriodicalIF":5.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.14127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758566","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}
Christian Diegritz, Christina Fotiadou, Felix Fleischer, Marcel Reymus
Aim
To develop and evaluate a suitable software application for mobile devices designed for teaching root canal anatomy to undergraduate students in an informative and engaging manner.
Methodology
Extracted human teeth were scanned by μCT and digitized by converting into STL files. An extended reality (XR) application illustrating the root canal anatomy of the scanned teeth was developed. Prior to deployment, undergraduate dental students were voluntarily asked about their expectations regarding an educational application on tooth anatomy. After a testing phase of the application on a mobile device and within a virtual reality environment, a subsequent evaluation was conducted to assess their overall experience in relation to their initial expectations. Data were analysed using Kolmogorov-Smirnov test and Mann-Whitney U test. The level of significance was set to .05 (p = .05).
Results
The application was able to meet the expectations of the students in all categories (p < .466–.731). Furthermore, it was evaluated as user-friendly (98.2%) and highly motivating for the purpose of learning more on root canal anatomy (100%).
Conclusion
Given the overwhelmingly positive reception from undergraduate dental students, the application emerges to be a promising supplementary teaching method for the endodontic curriculum.
{"title":"Tooth Anatomy Inspector: A comprehensive assessment of an extended reality (XR) application designed for teaching and learning of root canal anatomy by students","authors":"Christian Diegritz, Christina Fotiadou, Felix Fleischer, Marcel Reymus","doi":"10.1111/iej.14124","DOIUrl":"10.1111/iej.14124","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To develop and evaluate a suitable software application for mobile devices designed for teaching root canal anatomy to undergraduate students in an informative and engaging manner.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Extracted human teeth were scanned by μCT and digitized by converting into STL files. An extended reality (XR) application illustrating the root canal anatomy of the scanned teeth was developed. Prior to deployment, undergraduate dental students were voluntarily asked about their expectations regarding an educational application on tooth anatomy. After a testing phase of the application on a mobile device and within a virtual reality environment, a subsequent evaluation was conducted to assess their overall experience in relation to their initial expectations. Data were analysed using Kolmogorov-Smirnov test and Mann-Whitney <i>U</i> test. The level of significance was set to .05 (<i>p</i> = .05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The application was able to meet the expectations of the students in all categories (<i>p</i> < .466–.731). Furthermore, it was evaluated as user-friendly (98.2%) and highly motivating for the purpose of learning more on root canal anatomy (100%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Given the overwhelmingly positive reception from undergraduate dental students, the application emerges to be a promising supplementary teaching method for the endodontic curriculum.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 11","pages":"1682-1688"},"PeriodicalIF":5.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.14124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751634","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}
Shengyan Yang, Andy Yu Pan Leung, Zheng Wang, Cynthia Kar Yung Yiu, Waruna Lakmal Dissanayaka
<div> <section> <h3> Aim</h3> <p>Lack of adequate mechanical strength and progressive shrinkage over time remain challenges in scaffold-free microtissue-based dental pulp regeneration. Surface collagen cross-linking holds the promise to enhance the mechanical stability of microtissue constructs and trigger biological regulations. In this study, we proposed a novel strategy for surface preconditioning microtissues using a natural collagen cross-linker, proanthocyanidin (PA). We evaluated its effects on cell viability, tissue integrity, and biomineralization of dental pulp stem cell (DPSCs)-derived 3D cell spheroids.</p> </section> <section> <h3> Methodology</h3> <p>Microtissue and macrotissue spheroids were fabricated from DPSCs and incubated with PA solution for surface collagen cross-linking. Microtissue viability was examined by live/dead staining and 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide (MTT) assay, with transverse dimension change monitored. Microtissue surface stiffness was measured by an atomic force microscope (AFM). PA-preconditioned microtissues and macrotissues were cultured under basal or osteogenic conditions. Immunofluorescence staining of PA-preconditioned microtissues was performed to detect dentin sialophosphoprotein (DSPP) and F-actin expressions. PA-preconditioned macrotissues were subjected to histological analysis, including haematoxylin–eosin (HE), alizarin red, and Masson trichrome staining. Immunohistochemistry staining was used to detect alkaline phosphatase (ALP) and dentin matrix acidic phosphoprotein 1 (DMP-1) expressions.</p> </section> <section> <h3> Results</h3> <p>PA preconditioning had no adverse effects on microtissue spheroid viability and increased surface stiffness. It reduced dimensional shrinkage for over 7 days in microtissues and induced a larger transverse-section area in the macrotissue. PA preconditioning enhanced collagen formation, mineralized nodule formation, and elevated ALP and DMP-1 expressions in macrotissues. Additionally, PA preconditioning induced higher F-actin and DSPP expression in microtissues, while inhibition of F-actin activity by cytochalasin B attenuated PA-induced dimensional change and DSPP upregulation.</p> </section> <section> <h3> Conclusion</h3> <p>PA surface preconditioning of DPSCs spheroids demonstrates excellent biocompatibility while effectively enhancing tissue structure stability and promoting biomineralization. This strategy strengthens tissue integrity in DPSC-derived spheroids and amplifies osteogenic differentiation potential, advancing scaffold-
目的：缺乏足够的机械强度和随着时间的推移逐渐收缩仍然是基于无支架微组织的牙髓再生所面临的挑战。表面胶原交联有望增强微组织构建物的机械稳定性并触发生物调节。在本研究中，我们提出了一种使用天然胶原交联剂原花青素（PA）对微组织进行表面预处理的新策略。我们评估了它对牙髓干细胞（DPSCs）衍生的三维细胞球体的细胞活力、组织完整性和生物矿化的影响：方法：用 DPSCs 制作微组织和大组织球体，并与 PA 溶液培养，以进行表面胶原交联。通过活/死染色和 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四氮唑（MTT）试验检测微组织的活力，并监测横向尺寸变化。微组织表面硬度由原子力显微镜（AFM）测量。在基础或成骨条件下培养 PA 预处理的微组织和大组织。对PA预处理的微组织进行免疫荧光染色，以检测牙本质糖磷蛋白（DSPP）和F-肌动蛋白的表达。对 PA 预处理的大组织进行组织学分析，包括血色素-伊红（HE）、茜素红和 Masson 三色染色。免疫组化染色用于检测碱性磷酸酶（ALP）和牙本质基质酸性磷酸蛋白1（DMP-1）的表达：结果：PA 预处理对微组织球体存活率无不良影响，并能增加表面硬度。在超过 7 天的时间里，它减少了微组织的尺寸收缩，并使大组织的横截面积增大。PA 预处理增强了大血管组织中胶原蛋白的形成、矿化结节的形成以及 ALP 和 DMP-1 表达的升高。此外，PA预处理诱导微组织中更高的F-肌动蛋白和DSPP表达，而细胞松弛素B对F-肌动蛋白活性的抑制减弱了PA诱导的尺寸变化和DSPP上调：结论：对 DPSCs 球形组织进行 PA 表面预处理具有良好的生物相容性，同时能有效增强组织结构的稳定性并促进生物矿化。这一策略加强了 DPSCs 球体的组织完整性，并增强了成骨分化潜力，从而推动了无支架组织工程在再生牙科中的应用。
{"title":"Proanthocyanidin surface preconditioning of dental pulp stem cell spheroids enhances dimensional stability and biomineralization in vitro","authors":"Shengyan Yang, Andy Yu Pan Leung, Zheng Wang, Cynthia Kar Yung Yiu, Waruna Lakmal Dissanayaka","doi":"10.1111/iej.14126","DOIUrl":"10.1111/iej.14126","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Lack of adequate mechanical strength and progressive shrinkage over time remain challenges in scaffold-free microtissue-based dental pulp regeneration. Surface collagen cross-linking holds the promise to enhance the mechanical stability of microtissue constructs and trigger biological regulations. In this study, we proposed a novel strategy for surface preconditioning microtissues using a natural collagen cross-linker, proanthocyanidin (PA). We evaluated its effects on cell viability, tissue integrity, and biomineralization of dental pulp stem cell (DPSCs)-derived 3D cell spheroids.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Microtissue and macrotissue spheroids were fabricated from DPSCs and incubated with PA solution for surface collagen cross-linking. Microtissue viability was examined by live/dead staining and 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide (MTT) assay, with transverse dimension change monitored. Microtissue surface stiffness was measured by an atomic force microscope (AFM). PA-preconditioned microtissues and macrotissues were cultured under basal or osteogenic conditions. Immunofluorescence staining of PA-preconditioned microtissues was performed to detect dentin sialophosphoprotein (DSPP) and F-actin expressions. PA-preconditioned macrotissues were subjected to histological analysis, including haematoxylin–eosin (HE), alizarin red, and Masson trichrome staining. Immunohistochemistry staining was used to detect alkaline phosphatase (ALP) and dentin matrix acidic phosphoprotein 1 (DMP-1) expressions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PA preconditioning had no adverse effects on microtissue spheroid viability and increased surface stiffness. It reduced dimensional shrinkage for over 7 days in microtissues and induced a larger transverse-section area in the macrotissue. PA preconditioning enhanced collagen formation, mineralized nodule formation, and elevated ALP and DMP-1 expressions in macrotissues. Additionally, PA preconditioning induced higher F-actin and DSPP expression in microtissues, while inhibition of F-actin activity by cytochalasin B attenuated PA-induced dimensional change and DSPP upregulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PA surface preconditioning of DPSCs spheroids demonstrates excellent biocompatibility while effectively enhancing tissue structure stability and promoting biomineralization. This strategy strengthens tissue integrity in DPSC-derived spheroids and amplifies osteogenic differentiation potential, advancing scaffold-","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 11","pages":"1639-1654"},"PeriodicalIF":5.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.14126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758567","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, Vellore Kannan Gopinath, Srinivasan Narasimhan, Anirudh B. Acharya, Paul M. H. Dummer, Clovis Mariano Faggion Jr
Introduction
In endodontics, the number of umbrella reviews has increased significantly over the last few years, but there is no evidence that they were methodologically sound. The aim of the current study was to appraise the methodological quality of umbrella reviews in endodontics, and to identify possible predictive factors associated with methodological quality.
Methods
Umbrella reviews published in the discipline of endodontics until December 2023 were included. The methodological quality of the reviews was evaluated using a checklist consisting of 11 items. Each item in the checklist was evaluated by two independent assessors who assigned a score of ‘1’ if it was fully addressed, ‘0.5’ if it was partially ddressed, and ‘0’ if it was not addressed. Bootstrapped multiple linear regression analysis was used to examine the association between the total scores awarded and five predictor variables (a priori protocol registration, year of publication, number of authors, journal impact factor (IF) and continent of the corresponding author). The statistical significance level was set as 5%.
Results
A total of 27 reviews were included. Ninety-six per cent of the reviews adequately reported: eligibility criteria for selecting the reviews, details of the reviews, techniques for assessing the risk of bias or methodological quality of the individual systematic reviews they included. Only 30% of the reviews adequately managed overlapping primary studies within individual systematic reviews. Among the five predictors analysed, a priori protocol registration and journals with IFs were associated with significantly greater total methodological quality scores.
Discussion
Several methodological shortcomings in the umbrella reviews published within the field of endodontics were revealed. Umbrella reviews published in journals with IFs and those with protocols registered a priori had significantly superior methodological quality scores.
Conclusion
In endodontics, authors intending to publish umbrella reviews should consider the limitations revealed in this study and follow the appropriate rules to ensure their reviews comply with the highest standards and provide accurate and dependable information and conclusions.
{"title":"Methodological quality of umbrella reviews in endodontics: A cross-sectional study","authors":"Venkateshbabu Nagendrababu, Vellore Kannan Gopinath, Srinivasan Narasimhan, Anirudh B. Acharya, Paul M. H. Dummer, Clovis Mariano Faggion Jr","doi":"10.1111/iej.14114","DOIUrl":"10.1111/iej.14114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>In endodontics, the number of umbrella reviews has increased significantly over the last few years, but there is no evidence that they were methodologically sound. The aim of the current study was to appraise the methodological quality of umbrella reviews in endodontics, and to identify possible predictive factors associated with methodological quality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Umbrella reviews published in the discipline of endodontics until December 2023 were included. The methodological quality of the reviews was evaluated using a checklist consisting of 11 items. Each item in the checklist was evaluated by two independent assessors who assigned a score of ‘1’ if it was fully addressed, ‘0.5’ if it was partially ddressed, and ‘0’ if it was not addressed. Bootstrapped multiple linear regression analysis was used to examine the association between the total scores awarded and five predictor variables (<i>a priori</i> protocol registration, year of publication, number of authors, journal impact factor (IF) and continent of the corresponding author). The statistical significance level was set as 5%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 27 reviews were included. Ninety-six per cent of the reviews adequately reported: eligibility criteria for selecting the reviews, details of the reviews, techniques for assessing the risk of bias or methodological quality of the individual systematic reviews they included. Only 30% of the reviews adequately managed overlapping primary studies within individual systematic reviews. Among the five predictors analysed, <i>a priori</i> protocol registration and journals with IFs were associated with significantly greater total methodological quality scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Several methodological shortcomings in the umbrella reviews published within the field of endodontics were revealed. Umbrella reviews published in journals with IFs and those with protocols registered <i>a priori</i> had significantly superior methodological quality scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In endodontics, authors intending to publish umbrella reviews should consider the limitations revealed in this study and follow the appropriate rules to ensure their reviews comply with the highest standards and provide accurate and dependable information and conclusions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 10","pages":"1422-1433"},"PeriodicalIF":5.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626642","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}
To evaluate the effect of systemic administration of propranolol on the severity of apical periodontitis (AP) in chronically stressed rats.
Methodology
Twenty-four 70-day-old male Wistar rats (Rattus norvegicus, albinus) were distributed into three groups (n = 8): rats with AP without stressful conditions (AP-Control), rats with AP and submitted to a chronic unpredictable stress (CUS) protocol (AP + S) and rats with AP and submitted to a CUS protocol treated with propranolol (AP + S + PRO). Stress procedures were applied daily until the end of the experiment. After 3 weeks of CUS, AP was induced in all groups by exposing the pulpal tissue of mandibular and maxillary first molars to the oral environment. Propranolol treatment was administered orally once a day for the entire period of the experiment. Rats were sacrificed at 42 days, and the blood was collected for stress biomarkers serum dosage by multiplex assay. Mandibles were removed and submitted to microtomography and histopathological analyses. Periapical tissue surrounding the upper first molar was homogenized and subjected to RT-PCR analysis to evaluate the mRNA expression of RANKL, TRAP and OPG. Parametric data were assessed using one-way ANOVA followed by Tukey's test while the nonparametric data were analysed by the Kruskal–Wallis followed by Dunn's test. Significance level was set at 5% (p < .05) for all assessed parameters.
Results
Micro-CT revealed statistically significant differences in bone resorption which was greater in the AP + S group (p < .05), but no differences were observed between the Control and AP + S + PRO groups (p > .05). The AP + S + PRO group had a lower intensity and extent of inflammatory infiltrate compared to the AP + S group with smaller areas of bone loss (p < 0.05). The gene expression of RANKL and TRAP was significantly higher in the stressed group AP + S compared to the control group (p < .05), and a significantly higher OPG expression was observed in AP + S + PRO compared to the AP + S group (p < .05).
Conclusions
Oral administration of propranolol had a significant effect on the AP severity in stressed rats, suggesting an anti-inflammatory effect and a protective role on bone resorption of AP in stressed animals. Further research is necessary to fully comprehend the underlying mechanisms.
目的：评估全身给药普萘洛尔对慢性应激大鼠根尖牙周炎（AP）严重程度的影响：将24只70天大的雄性Wistar大鼠（Rattus norvegicus, albinus）分为三组（n = 8）：无应激条件下患有牙尖周炎的大鼠（AP-对照组）、患有牙尖周炎并接受慢性不可预测应激（CUS）方案治疗的大鼠（AP + S组）和患有牙尖周炎并接受普萘洛尔治疗的CUS方案治疗的大鼠（AP + S + PRO组）。应激过程每天进行，直到实验结束。CUS 3 周后，将下颌和上颌第一磨牙的牙髓组织暴露于口腔环境中，诱发所有组的 AP。在整个实验期间，每天口服一次普萘洛尔。大鼠在42天时被处死，并采集血液通过多重分析法检测应激生物标志物血清剂量。取出大鼠下颌骨，进行显微断层扫描和组织病理学分析。将上第一磨牙周围的根尖周组织匀浆并进行 RT-PCR 分析，以评估 RANKL、TRAP 和 OPG 的 mRNA 表达。参数数据采用单因素方差分析，然后进行Tukey检验；非参数数据采用Kruskal-Wallis分析，然后进行Dunn检验。显著性水平设定为 5%（P 结果：显微 CT 显示，AP + S 组的骨吸收率更高（p .05），差异有统计学意义。与 AP + S 组相比，AP + S + PRO 组的炎症浸润强度和程度较低，骨质流失面积较小（P 结论：AP + S + PRO 组的骨质流失面积较小（P.05）：口服普萘洛尔对应激大鼠的 AP 严重程度有显著影响，这表明普萘洛尔具有抗炎作用，对应激动物 AP 的骨吸收具有保护作用。有必要开展进一步研究，以全面了解其潜在机制。
{"title":"Systemic administration of propranolol reduces bone resorption and inflammation in apical periodontitis of chronically stressed rats","authors":"Rayana Duarte Khoury, Giovanna Bignoto Minhoto, Patricia Pimentel de Barros, Juliana Campos Junqueira, Carolina Fedel Gagliardi, Renata Falchete do Prado, Marcia Carneiro Valera","doi":"10.1111/iej.14118","DOIUrl":"10.1111/iej.14118","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the effect of systemic administration of propranolol on the severity of apical periodontitis (AP) in chronically stressed rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Twenty-four 70-day-old male Wistar rats (<i>Rattus norvegicus</i>, <i>albinus</i>) were distributed into three groups (<i>n</i> = 8): rats with AP without stressful conditions (AP-Control), rats with AP and submitted to a chronic unpredictable stress (CUS) protocol (AP + S) and rats with AP and submitted to a CUS protocol treated with propranolol (AP + S + PRO). Stress procedures were applied daily until the end of the experiment. After 3 weeks of CUS, AP was induced in all groups by exposing the pulpal tissue of mandibular and maxillary first molars to the oral environment. Propranolol treatment was administered orally once a day for the entire period of the experiment. Rats were sacrificed at 42 days, and the blood was collected for stress biomarkers serum dosage by multiplex assay. Mandibles were removed and submitted to microtomography and histopathological analyses. Periapical tissue surrounding the upper first molar was homogenized and subjected to RT-PCR analysis to evaluate the mRNA expression of RANKL, TRAP and OPG. Parametric data were assessed using one-way ANOVA followed by Tukey's test while the nonparametric data were analysed by the Kruskal–Wallis followed by Dunn's test. Significance level was set at 5% (<i>p</i> < .05) for all assessed parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Micro-CT revealed statistically significant differences in bone resorption which was greater in the AP + S group (<i>p</i> < .05), but no differences were observed between the Control and AP + S + PRO groups (<i>p</i> > .05). The AP + S + PRO group had a lower intensity and extent of inflammatory infiltrate compared to the AP + S group with smaller areas of bone loss (<i>p</i> < 0.05). The gene expression of RANKL and TRAP was significantly higher in the stressed group AP + S compared to the control group (<i>p</i> < .05), and a significantly higher OPG expression was observed in AP + S + PRO compared to the AP + S group (<i>p</i> < .05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Oral administration of propranolol had a significant effect on the AP severity in stressed rats, suggesting an anti-inflammatory effect and a protective role on bone resorption of AP in stressed animals. Further research is necessary to fully comprehend the underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 10","pages":"1478-1491"},"PeriodicalIF":5.4,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603584","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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