{"title":"27-Hydroxycholesterol contributes to hypercholesterolemia-associated aggravation of apical periodontitis in ovariectomized rats and raloxifene counteracts its action","authors":"H.-W. Wang, C.-N. Yang, S.-H. Kok, C.-Y. Hong, C.-T. Shun, E. H.-H. Lai, S.-J. Cheng, H.-Y. Lin, F.-Y. Wu, S.-K. Lin","doi":"10.1111/iej.14143","DOIUrl":"10.1111/iej.14143","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The influence of hypercholesterolemia on the development of apical periodontitis (AP) is inconclusive. Recent studies revealed that cholesterol metabolite 27-hydoxycholesterol (27HC) can affect cellular responses to bacterial infections and oestrogen status and raloxifene may influence its action. Herein, we aimed to examine the impact of 27HC on production of inflammatory mediators by macrophages and the regulatory function of raloxifene. The contribution of 27HC to AP development and the therapeutic effect of raloxifene were evaluated in a rat model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Murine macrophages J774 cells were used. The expression of inducible nitric oxide synthase (iNOS) was examined by Western blot. The concentrations of C-C motif chemokine ligand (CCL) 2 and 27HC were assessed by enzyme-linked immunosorbent assay. Colorimetric assay was used to evaluate cholesterol levels. Experimental AP was induced in ovariectomized (OVX) or un-operated rats receiving high-fat/high-cholesterol diet (HFHCD) or normal diet (ND). Micro-computed tomography and immunohistochemistry were employed to evaluate disease severity and the therapeutic effect of raloxifene.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cholesterol enhanced 27HC production in macrophages. 27HC induced iNOS and CCL2 synthesis by macrophages and estradiol suppressed the responses. In our animal model of AP, HFHCD plus OVX significantly augmented serum and lesion tissue levels of 27HC (<i>p</i> < .05 versus the ND group). Lesion size, infiltration of CD68<sup>+</sup> cells, and iNOS<sup>+</sup> monocytes were increased in parallel with 27HC accumulation. Raloxifene inhibited pro-inflammatory effects of 27HC on macrophages and suppressed AP progression in HFHCD/OVX rats (<i>p</i> < .05 versus the vehicle control group).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results suggested that 27HC contributes to AP aggravation associated with hypercholesterolemia. Oestrogen deficiency may both enhance 27HC production and exacerbate its downstream action.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"58 1","pages":"97-110"},"PeriodicalIF":5.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205749","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}
{"title":"Macrophage polarization in human periapical lesions in relation to histopathological diagnosis, clinical features and lesion volume: An ex vivo study","authors":"Supanant Visarnta, Chootima Ratisoontorn, Anchana Panichuttra, Phonkit Sinpitaksakul, Soranun Chantarangsu, Kittipong Dhanuthai","doi":"10.1111/iej.14138","DOIUrl":"10.1111/iej.14138","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate M1 and M2 macrophage polarization in radicular cysts and periapical granulomas through an immunohistochemical analysis and the correlation between macrophage polarization and histopathological diagnosis, clinical characteristics and lesion volume using cone-beam computed tomography.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Periapical biopsies diagnosed as radicular cysts (<i>n</i> = 52) and periapical granulomas (<i>n</i> = 51) were analysed by immunohistochemical method. Teeth with periapical lesion with no history of root canal treatment (primary lesion) and lesions persistent to root canal treatment (persistent lesions) were included. Pathological diagnosis, patients' age, gender and clinical characteristics were obtained from treatment records. A cone-beam computed tomographic periapical volume index (CBCTPAVI) score was assigned to each periapical lesion based on the volume of the lesion. Immuno-expressions of CD68 and CD163 were quantified. The CD68/CD163 ratio was adopted to represent M1 or M2 macrophage polarization. Mann–Whitney <i>U</i> test was used to determine the different CD68/CD163 ratio between groups of radicular cyst and periapical granuloma. Spearman's correlation test was performed to assess the correlation between the CD68/CD163 ratio and lesion volume and CBCTPAVI score.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Radicular cysts and periapical granulomas had CD68/CD163 median of 2.05 (IQR = 1.33) and 1.26 (IQR = 0.81), respectively. A significantly higher CD68/CD163 ratio was observed in radicular cysts (<i>p</i> < .001). In contrast, periapical granulomas had significantly lower median of CD68/CD163 ratio. Larger lesions had a higher median of CD68/CD163 ratio, while smaller lesions had lower median of CD68/CD163 ratio (<i>p</i> = .007, <i>r</i><sub>s</sub> = .262). CD68/CD163 ratio was significantly correlated with the CBCTPAVI score in the overall periapical lesions (<i>p</i> = .002, <i>r</i><sub>s</sub> = .306). The higher CD68/CD163 ratio in larger lesions indicated a higher degree of M1 polarization compared to smaller lesions. Regarding the pathological diagnosis, there was a significant positive correlation between CBCTPAVI score and CD68/CD163 ratio in periapical granulomas (<i>p</i> < .001, <i>r</i><sub>s</sub> = .453), whereas the negative correlation was observed for radicular cysts (<i>p</i> < .001, <i>r</i><sub>s</sub> = −.471).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Periapical granulomas are characterized by a M2-dominant macrophage polarization, while radicular cysts have significantly higher M1 macrophages. The high","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 12","pages":"1829-1847"},"PeriodicalIF":5.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107084","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}
Lidiane Mendes Louzada, Rodrigo Arruda-Vasconcelos, Michaela Kearney, Yukako Yamauchi, Brenda P. F. A. Gomes, Henry F. Duncan
{"title":"Teeth with vital pulps and stage III periodontitis unresponsive to therapy exhibit a pulpal inflammatory profile similar to symptomatic irreversible pulpitis","authors":"Lidiane Mendes Louzada, Rodrigo Arruda-Vasconcelos, Michaela Kearney, Yukako Yamauchi, Brenda P. F. A. Gomes, Henry F. Duncan","doi":"10.1111/iej.14139","DOIUrl":"10.1111/iej.14139","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The aim of this study is to investigate the expression of inflammatory biomarkers (TNF-α, IL-10, IL-1β) and the pulpitis-associated miRNA (miR-30a-5p and miR-128-3p) in pulp tissue samples from unrestored teeth with a vital normal pulp (NP), teeth with symptomatic irreversible pulpitis (IP) and in unrestored teeth with periodontal disease, unresponsive to periodontal therapy, and a vital pulp (EP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Thirty patients were included in this observational study (10 teeth with NP, 10 teeth with IP, 10 teeth with EP). Dental pulp tissues samples were collected from patients during root canal treatment (RCT). RNA was extracted and qRT-PCR of target genes (tumour necrosis factor [TNF]-α, interleukin [IL]-1β, IL-10) and miRNAs (has-miR-30a-5p, has-miR-128-3p) performed to assess the expression profile. Fold-change in expression was calculated using the formula 2<sup>−(ΔCt(Exp)−ΔCt(Ctrl))</sup>. One-way <span>anova</span> with post-hoc Tukey's was used to determine significant differences between groups. The significance level was set at 5% (<i>p</i> < .05). All teeth were also followed up clinically for 1 year and evaluated for a range of endodontic and periodontal-related outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All investigated genes significantly increased in expression and miRNAs significantly decreased in expression in the IP and EP groups compared with the NP group (<i>p</i> < .05). With regards to TNF-α and IL-1β there were no significant differences in expression between the IP and EP groups (<i>p</i> > .05), whereas IL-10 expression levels were significantly reduced in the EP compared with the IP group (<i>p <</i> .05). Both miR-30a-5p and miR-128-3p showed significantly reduced expression in both IP and EP lesions, compared with NP (<i>p</i> < .05); however, no significant differences in miRNA expression were observed between IP and EP groups (<i>p</i> > .05). One year after root canal treatment and periodontal maintenance, tooth mobility and probing depth were significantly reduced in the EP group (<i>p</i> < .05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Pulp tissues from teeth with IP and EP presented similar levels of altered inflammatory markers compared with NP. <i>TNF-</i>α, <i>IL-10</i>, <i>IL-1β</i> cytokines and miRNAs (miR-30a-5p and miR-128-3p) are potential objective biomarkers to indicate pulpal inflammatory status, aiding diagnosis and directing clinical decision-making. RCT may be beneficial to improve stage ","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 12","pages":"1769-1782"},"PeriodicalIF":5.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.14139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072710","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}
Filipe Colombo Vitali, Gabriel Mafra, Pablo Silveira Santos, Lucas da Fonseca Roberti Garcia, Cleonice da Silveira Teixeira
{"title":"Patient-related predictors of post-operative pain following root canal treatment: A structural model analysis","authors":"Filipe Colombo Vitali, Gabriel Mafra, Pablo Silveira Santos, Lucas da Fonseca Roberti Garcia, Cleonice da Silveira Teixeira","doi":"10.1111/iej.14137","DOIUrl":"10.1111/iej.14137","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The pathways to post-operative pain are complex and encompass factors that extend beyond the treatment protocol employed. This study aimed to identify patient-related predictors of post-operative pain following root canal treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>A total of 154 patients received a single-visit root canal treatment for asymptomatic necrotic mandibular molars. Before treatment, dental anxiety, dental fear and sense of coherence (SOC) were measured as predictors for each patient using validated questionnaires. Other measured predictors included gender, age, previous negative experiences at the dental offices and prior root canal treatment. Post-operative pain was assessed using the Numeric Rating Scale at multiple time-points over 30 days. Structural equation analysis was employed to evaluate the direct and indirect effects of patient-related predictors on a theoretical model of post-operative pain. The irrigant solution was also included in the model, as it was the only aspect that varied in the treatment protocol (sodium hypochlorite 2.5% and 8.25%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Dental anxiety (coefficient 0.028; <i>p</i> < .01), dental fear (coefficient 0.007; <i>p</i> = .02) and irrigant solution (coefficient 0.004; <i>p</i> = .03) exerted a direct effect on post-operative pain. SOC exerted an indirect effect on post-operative (coefficient 0.006; <i>p</i> = .01) through dental anxiety and dental fear. Moreover, previous negative experiences (coefficient 0.048; <i>p</i> = .04) exerted an indirect effect on post-operative pain through dental anxiety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Dental anxiety, dental fear, previous negative experiences and SOC are patient-related predictors of post-operative pain following root canal treatment. These factors should be taken into consideration in clinical practice, as patients with these characteristics may be at an increased risk of experiencing post-operative pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 12","pages":"1758-1768"},"PeriodicalIF":5.4,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987899","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}
Arvid Dahlstrand Rudin, Agnes Dahlstrand Rudin, Charlotte Ulin, Thomas Kvist
{"title":"The use of 0.5% or 3% NaOCl for irrigation during root canal treatment results in similar clinical outcome: A 6-year follow-up of a quasi-randomized clinical trial","authors":"Arvid Dahlstrand Rudin, Agnes Dahlstrand Rudin, Charlotte Ulin, Thomas Kvist","doi":"10.1111/iej.14134","DOIUrl":"10.1111/iej.14134","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate the 6-year outcome of root canal treatment irrigated with 0.5% or 3% sodium hypochlorite (NaOCl).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>The baseline trial was designed as a quasi-randomized clinical trial. Patients referred for root canal treatment to an endodontic specialist clinic were recruited to the study (<i>n</i> = 298). The concentration of NaOCl was allocated quasi-randomized to 271 subjects (0.5% [<i>n</i> = 139], 3% [<i>n</i> = 132]). Bacterial sampling was performed immediately before root canal filling. Samples were cultured and evaluated as growth or no growth. Patients were invited to a clinical and radiological follow-up >5 years postoperatively. The clinical outcome measurements were tooth survival, cumulative incidence of endodontic retreatments, patients' assessment of pain, clinical findings and radiological signs of apical periodontitis (AP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Tooth survival was 85.6% in the 0.5% NaOCl group and 81.1% in the 3% NaOCl group (<i>p</i> = .45). There was no record of retreatment in 94.4% in the 0.5% NaOCl group and in 92.2% in the 3% NaOCl group (<i>p</i> = .76). The percentage of asymptomatic cases were 87.8% in the 0.5% group and 85.3% in the 3% NaOCl group (<i>p</i> = .81). Absence of clinical signs of AP was seen in 86.6% in the 0.5% NaOCl group and in 83.6% in the 3% NaOCl group (<i>p</i> = .80). Absence of radiological signs of AP was seen in 74.0% in the 0.5% NaOCl group and 64.1% in the 3% NaOCl group (<i>p</i> = .20). Subjects with positive culture before root filling reported subjective pain with a significantly higher frequency as compared to negative-culture subjects (<i>p</i> = .014).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The use of 0.5% or 3% NaOCl for irrigation during root canal treatment resulted in similar clinical outcomes 5–7 years postoperatively. Persisting bacteria immediately before root filling may predict future episodes of subjective pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 12","pages":"1745-1757"},"PeriodicalIF":5.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iej.14134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916617","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}
J. A. Gallas, L. L. Pelozo, S. A. M. Corona, Y. Shen, M. Haapasalo, M. D. Sousa-Neto, A. E. Souza-Gabriel
{"title":"Effect of pomegranate solution alone or combined with chlorhexidine against oral multispecies biofilm","authors":"J. A. Gallas, L. L. Pelozo, S. A. M. Corona, Y. Shen, M. Haapasalo, M. D. Sousa-Neto, A. E. Souza-Gabriel","doi":"10.1111/iej.14135","DOIUrl":"10.1111/iej.14135","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Natural bioactive products have been tested as alternative antimicrobial agents. This study evaluated the effect of <i>Punica granatum</i> extract (PGE) on oral multispecies biofilms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Lyophilized extracts from pomegranate peel were prepared, and the punicalagin content was assessed by ultra-performance liquid chromatography (UPLC). Oral multispecies biofilms from 2 donors were grown on four collagen-coated hydroxyapatite discs. After incubation for 7 days or 3 weeks, the biofilms were exposed to water (control), 2% CHX, 10% PGE, 20% PGE or 30% PGE for 3 min. The proportions of dead bacteria were assessed by the live/dead staining and confocal microscopy. After the analysis, the best PGE concentration (30%) was combined with CHX. The experimental phases were repeated using water, 2% CHX, 30% PGE and 30% PGE + 2% CHX. Five random areas of the biofilm on each disc were scanned, resulting in 20 scanned areas for each group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Regarding the biofilm volume, no differences were found amongst solutions (<i>p</i> = .111). The PGE solution killed bacteria effectively in 1-week, 2-week and 3-week-old-plaque biofilms, ranging from 37 to 55.3%, depending on the PGE concentration. The 30% PGE (a) (<i>p</i> = .0009) had greater antibiofilm effectiveness than 2% CHX (b), which killed bacteria in the 25.2 to 48.7% range. The 10% and 20% PGE had intermediate values (ab), without significant differences from 30% PGE (<i>p</i> = 1.002). Water (c) had the lowest proportion of dead bacteria (<i>p</i> < .00001) in a range of 5 to 6.7% and lower effectiveness in killing bacteria (<i>p</i> < .05). The PGE alone or mixed with 2% CHX had greater anti-biofilm effectiveness than CHX (<i>p</i> < .05). The old plaque biofilms were more resistant than the 7-day-old plaque (<i>p</i> < .05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The 30% PGE (alone or combined with CHX) exhibited a greater antibiofilm effect on oral multispecies biofilms grown on hydroxyapatite discs than 2% CHX.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 12","pages":"1819-1828"},"PeriodicalIF":5.4,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912528","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}
Zijun Meng, Xiaoyi Zhong, Dan Liang, Xuemeng Ma, Wenxia Chen, Xuan He
{"title":"MiR-143-5p regulates the proangiogenic potential of human dental pulp stem cells by targeting HIF-1α/RORA under hypoxia: A laboratory investigation in pulp regeneration","authors":"Zijun Meng, Xiaoyi Zhong, Dan Liang, Xuemeng Ma, Wenxia Chen, Xuan He","doi":"10.1111/iej.14133","DOIUrl":"10.1111/iej.14133","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Angiogenesis is a key event in the successful healing of pulp injuries, and hypoxia is the main stimulator of pulpal angiogenesis. In this study, we investigated the effect of hypoxia on the proangiogenic potential of human dental pulp stem cells (hDPSCs) and the role of miR-143-5p in the process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Human dental pulp stem cells were isolated, cultured and characterized in vitro. Cobalt chloride (CoCl<sub>2</sub>) was used to induce hypoxia in hDPSCs. CCK-8 and Transwell assays were used to determine the effect of hypoxia on hDPSCs proliferation and migration. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting (WB) and ELISA were performed to assess the mRNA and protein levels of HIF-1α and angiogenic cytokines in hDPSCs. The effect of hypoxia on hDPSCs proangiogenic potential was measured in vitro using Matrigel tube formation and chick chorioallantoic membrane (CAM) assays. Recombinant lentiviral vectors were constructed to stably overexpress or inhibit miR-143-5p in hDPSCs, and the proangiogenic effects were assessed using qRT-PCR, WB, and tube formation assays. miR-143-5p target genes were identified and verified using bioinformatics prediction tools, dual-luciferase reporter assays and RNA pull-down experiments. Finally, a subcutaneous transplantation model in nude mice was used to determine the effects of hypoxia treatment and miR-143-5p overexpression/inhibition in hDPSCs in dental pulp regeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hypoxia promotes hDPSCs proliferation, migration and proangiogenic potential. The in vivo experiments showed that hypoxia treatment (50 and 100 μM CoCl<sub>2</sub>) promoted pulp angiogenesis and dentine formation. In contrast to the levels of proangiogenic factors, miR-143-5p levels decreased with increasing CoCl<sub>2</sub> concentration. miR-143-5p inhibition significantly promoted proangiogenic potential of hDPSCs, whereas miR-143-5p overexpression inhibited angiogenesis in vitro. Dual-luciferase reporter assay identified retinoic acid receptor-related orphan receptor alpha (RORA) as an miR-143-5p target gene in hDPSCs. RNA pull-down experiments demonstrated that HIF-1α and RORA were pulled down by biotin-labelled miR-143-5p, and the levels of HIF-1α and RORA bound to miR-143-5p in the hypoxia group were lower than those in the normoxia group. Inhibition of miR-143-5p expression in hDPSCs promoted ectopic dental pulp tissue regeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CoCl<sub>2</sub>-induced hypoxia promotes hDPSCs-driven paracrine angiogenesis and pulp r","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"57 12","pages":"1802-1818"},"PeriodicalIF":5.4,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912529","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}
Yuan-Hao Wen, Yu-Xiu Lin, Lu Zhou, Chen Lin, Lu Zhang
{"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
{"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
{"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}