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Fernández A, Bendek MJ, Bordagaray MJ, Ramírez V, Chaparro A, Hernández M. Exploring the regulatory roles of MicroRNAs on NF- ΚB target genes in individuals with apical periodontitis. Clin Oral Investig 2025; 29:251. [PMID: 40237848 DOI: 10.1007/s00784-025-06280-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 03/12/2025] [Indexed: 04/18/2025]
Abstract
OBJECTIVES This study investigated the association of miRNA-181-5p, miRNA-150-5p, miRNA-146a-5p, and miRNA-16-5p, and inflammatory genes linked to the NF-κB pathway in patients with symptomatic and asymptomatic apical periodontitis. MATERIALS AND METHODS A cross-sectional study was conducted involving apical tissues from asymptomatic apical periodontitis (AAP, n = 17), symptomatic apical periodontitis (SAP, n = 15), and healthy periodontal ligament (HPL, n = 16). Expression levels of miRNA-181-5p, miRNA-150-5p, miRNA-146a-5p, and miRNA-16-5p, along with mRNA levels of IL-6, VEGF-A, HIF-1α, and NF-κB, were quantified using qPCR. Data were analyzed through descriptive statistics and regression models, including mediation analysis conducted using STATA V14 (p < 0.05). RESULTS mRNA levels of IL-6, VEGF-A, and NF-κB were significantly higher in SAP compared to HPL (p < 0.05), while AAP did not show differences (p > 0.05). Also, no significant differences were observed in HIF-1α expression among the groups (p > 0.05). miRNA-181-5p, miRNA-16-5p, and miRNA-146a-5p were downregulated in both AAP and SAP, compared to HPL (p < 0.05), whereas miRNA-150-5p was upregulated (p < 0.05). Negative correlations were found between miRNA-181-5p and miRNA-16-5p with IL-6, and between miRNA-181-5p and VEGF-A in AP forms (p < 0.05). Mediation analysis revealed that the upregulation of IL-6 mRNA was mediated by miRNA-16-5p in SAP. CONCLUSIONS Apical periodontitis is associated with the downregulation of miRNA-181-5p, miRNA-16-5p, and miRNA-146a-5p and the upregulation of miRNA-150-5p. IL-6 mRNA levels seem to be regulated by miRNA-16-5p during SAP. CLINICAL RELEVANCE This study provides insights into the molecular mechanisms and the inflammatory response in apical periodontitis (AP), differentiating between asymptomatic (AAP) and symptomatic forms (SAP). By identifying the specific roles of miRNAs-particularly miRNA-181-5p, miRNA-150-5p, miRNA-146a-5p, and miRNA-16-5p-on inflammation-related genes via the NF-κB pathway, the findings highlight potential diagnostic and therapeutic targets. Notably, SAP is associated with downregulation of miRNA-181-5p, miRNA-16-5p, and miRNA-146a-5p, alongside upregulation of miRNA-150-5p. The study reveals that miRNA-16-5p may modulate IL-6 gene expression during SAP, which can exacerbate inflammation and osteoclastogenesis in the affected tissues. Understanding the gene regulation of inflammatory mediators in AP can aid clinicians in personalizing management approaches, particularly in cases where traditional diagnostic methods fall short. This molecular perspective may also pave the way for miRNA-based interventions, enhancing patient outcomes by specifically targeting the inflammatory pathways underlying AP pathology.
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Affiliation(s)
- Alejandra Fernández
- Faculty of Dentistry, Universidad Andres Bello, Echaurren 237, Santiago, 8370133, Chile
| | - María José Bendek
- PhD Program in Biomedicine, School of Medicine, Universidad de Los Andes, Monseñor Álvaro del Portillo 12455, Santiago, 7620157, Chile
- Department of Periodontology, Pathology, and Conservative Dentistry, Centre for Biomedical Research and Innovation, Faculty of Dentistry, Universidad de Los Andes, Av. Plaza 2501, Santiago, 7620157, Chile
| | - María José Bordagaray
- Laboratory of Periodontal Biology, Faculty of Dentistry, University of Chile, Olivos 943, Independencia, Santiago, 8380544, Chile
- Department of Conservative Dentistry, Faculty of Dentistry, Universidad de Chile, Olivos 943, Independencia, Santiago, 8380544, Chile
| | - Valeria Ramírez
- Department of Biomedical Sciences, Ethics, Research and Education, Faculty of Dentistry, Universidad de Los Andes, Monseñor Álvaro del Portillo 12455, Santiago, 7620157, Chile
| | - Alejandra Chaparro
- Department of Periodontology, Pathology, and Conservative Dentistry, Centre for Biomedical Research and Innovation, Faculty of Dentistry, Universidad de Los Andes, Av. Plaza 2501, Santiago, 7620157, Chile.
| | - Marcela Hernández
- Laboratory of Periodontal Biology, Faculty of Dentistry, University of Chile, Olivos 943, Independencia, Santiago, 8380544, Chile.
- Department of Pathology and Oral Medicine, Faculty of Dentistry, University of Chile, Olivos 943, Independencia, Santiago, 8380544, Chile.
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Li C, Sun Y. Investigation of chromatin remodeling-related biomarkers and associated molecular mechanism in pulpitis. Gene 2025; 934:149016. [PMID: 39433267 DOI: 10.1016/j.gene.2024.149016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 09/26/2024] [Accepted: 10/16/2024] [Indexed: 10/23/2024]
Abstract
The current study aimed to identify potential chromatin remodeling-related biomarkers and the associated molecular mechanisms in pulpitis. Differentially expressed genes associated with chromatin remodeling (DECRGs) were identified using datasets from an online database. Enrichment and protein-protein interaction (PPI) network analyses were performed based on the DECRGs to identify biomarkers for pulpitis, followed by GSEA (gene set enrichment analysis). The diagnostic value of these biomarkers were evaluated by ROC (Receiver operating characteristic) and nomogram investigation. Next, microRNA(miRNA)-mRNA-TF (transcription factor), ceRNA (competing endogenous RNA), and drug prediction networks were constructed based on the biomarkers. Finally, reverse transcription-real-time quantitative PCR analysis and western blot were performed to validate the results of the bioinformatic analysis. This study identified 87 DECRGs between pulpitis and normal dental pulp samples that were mainly enriched in chromatin remodeling functions and pathways in cancer. A PPI network identified five biomarkers: TNF, STAT3, MYC, ACTB, and MAPK8. ROC and nomogram analyses demonstrated the diagnostic value of these biomarkers. GSEA of biomarkers such as STAT3 was mainly enriched in functions such as the B cell receptor signaling pathway. A biomarker-disease network and miRNA-mRNA-TF interactions were constructed using these biomarkers. A ceRNA network was constructed with interactions including chr22-38_28785274-29006793.1-miR-125b-5p-STAT3. A drug-gene network was established using 170 drugs and five biomarkers. Finally, qRT-PCR was used to validate the expression of all five biomarkers identified by the bioinformatics analysis. TNF, STAT3, MYC, ACTB, and MAPK8 are potential chromatin remodeling-related diagnostic markers for pulpitis. Moreover, long non-coding RNA (lncRNA) chr22-38_28785274-29006793.1 might function as a ceRNA to regulate the expression of the chromatin remodeling gene STAT3 by sponging miR-125b-5p in pulpitis.
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Affiliation(s)
- Chenglin Li
- Department of Stomatology, Sunshine Union Hospital, Weifang 261000, China
| | - Yujiao Sun
- Department of Stomatology, Sunshine Union Hospital, Weifang 261000, China.
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Li Q, Zhu JJ. Expression Levels of miR-181 Family Members in Oral Biofluids as Biomarkers for Periodontitis Severity. TOHOKU J EXP MED 2024; 264:121-130. [PMID: 38960640 DOI: 10.1620/tjem.2024.j058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/05/2024]
Abstract
This study aimed to assess the diagnostic potential of microRNA-181 (miR-181) family members in oral biofluids, namely saliva and gingival crevicular fluid (GCF), as biomarkers for periodontitis severity. A cohort of 150 patients with periodontitis, including 82 with mild to moderate and 68 with advanced periodontitis, along with 90 healthy controls, were recruited. Analysis of miR-181 family expression using quantitative real-time polymerase chain reaction (qRT-PCR) revealed differential expression levels in oral biofluids among the study groups. Salivary miRNAs, particularly miR-181a, displayed significant discriminatory ability in distinguishing periodontitis patients from healthy controls and between different stages of periodontitis severity, with high sensitivity and moderate to high specificity. In GCF samples, miR-181a and miR-181b exhibited robust discriminatory ability, while miR-181c showed moderate discriminatory ability. Conversely, miR-181d demonstrated lower discriminatory power in both saliva and GCF. Additionally, combination diagnosis using miR-181 family showed superior performance compared to individual miRNAs. Furthermore, enzyme-linked immunosorbent assay (ELISA) analysis of inflammatory biomarkers (TNF-α, IL-6, and IL-1β) in GCF revealed elevated levels in periodontitis patients compared to healthy controls, with a further increase observed in advanced periodontitis. Spearman correlation analysis demonstrated a significant negative correlation between miR-181 family expression in GCF and inflammatory biomarker levels, indicating their potential role in modulating periodontal inflammation. Overall, these findings suggest that miR-181 family members in oral biofluids, particularly saliva, hold promise as diagnostic biomarkers for periodontitis severity. Additionally, their negative correlation with inflammatory biomarkers highlights their potential as modulators of periodontal inflammation, providing valuable insights into the pathogenesis of periodontitis.
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Affiliation(s)
- Qun Li
- Department of Stomatology, China Resources and WISCO General Hospital
| | - Jin-Juan Zhu
- Department of Stomatology, China Resources and WISCO General Hospital
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Li Y, Guo X, Yao H, Zhang Z, Zhao H. Epigenetic control of dental stem cells: progress and prospects in multidirectional differentiation. Epigenetics Chromatin 2024; 17:37. [PMID: 39623487 PMCID: PMC11613947 DOI: 10.1186/s13072-024-00563-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 11/26/2024] [Indexed: 12/06/2024] Open
Abstract
Dental stem cells, with their exceptional proliferative capacity and multidirectional differentiation potential, hold significant promise for dental and oral tissue regeneration. Epigenetic inheritance, which involves stable and heritable changes in gene expression and function without alterations to the DNA sequence, plays a critical role in numerous biological processes. Environmental factors are particularly influential in epigenetic inheritance, as variations in exposure can lead to changes in epigenetic modifications that subsequently impact gene expression. Epigenetic mechanisms are widely involved in processes such as bone homeostasis, embryogenesis, stem cell fate determination, and disease development. Recently, the epigenetic regulation of dental stem cells has attracted considerable research attention. This paper reviews studies focused on the epigenetic mechanisms governing the multidirectional differentiation of dental stem cells.
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Affiliation(s)
- Yan Li
- Hospital of Stomatology, Jilin University, Changchun, 130021, China
| | - Xinwei Guo
- Department of Stomatology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Hua Yao
- Department of Stomatology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Zhimin Zhang
- Hospital of Stomatology, Jilin University, Changchun, 130021, China.
| | - Hongyan Zhao
- Hospital of Stomatology, Jilin University, Changchun, 130021, China.
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Louzada LM, Arruda-Vasconcelos R, Kearney M, Yamauchi Y, Gomes BPFA, Duncan HF. Teeth with vital pulps and stage III periodontitis unresponsive to therapy exhibit a pulpal inflammatory profile similar to symptomatic irreversible pulpitis. Int Endod J 2024; 57:1769-1782. [PMID: 39189896 DOI: 10.1111/iej.14139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 06/26/2024] [Accepted: 08/12/2024] [Indexed: 08/28/2024]
Abstract
AIM 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). METHODOLOGY 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-(ΔCt(Exp)-ΔCt(Ctrl)). One-way anova with post-hoc Tukey's was used to determine significant differences between groups. The significance level was set at 5% (p < .05). All teeth were also followed up clinically for 1 year and evaluated for a range of endodontic and periodontal-related outcomes. RESULTS All investigated genes significantly increased in expression and miRNAs significantly decreased in expression in the IP and EP groups compared with the NP group (p < .05). With regards to TNF-α and IL-1β there were no significant differences in expression between the IP and EP groups (p > .05), whereas IL-10 expression levels were significantly reduced in the EP compared with the IP group (p < .05). Both miR-30a-5p and miR-128-3p showed significantly reduced expression in both IP and EP lesions, compared with NP (p < .05); however, no significant differences in miRNA expression were observed between IP and EP groups (p > .05). One year after root canal treatment and periodontal maintenance, tooth mobility and probing depth were significantly reduced in the EP group (p < .05). CONCLUSION Pulp tissues from teeth with IP and EP presented similar levels of altered inflammatory markers compared with NP. TNF-α, IL-10, IL-1β 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 III periodontitis unresponsive to non-surgical periodontal treatment, but further research is required.
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Affiliation(s)
- Lidiane Mendes Louzada
- Department of Restorative Dentistry, Division of Endodontics, Piracicaba Dental School, State University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil
- Division of Restorative Dentistry and Periodontology, Trinity College Dublin, Dublin Dental University Hospital, Dublin, Ireland
| | - Rodrigo Arruda-Vasconcelos
- Department of Restorative Dentistry, Division of Endodontics, Piracicaba Dental School, State University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil
| | - Michaela Kearney
- Division of Restorative Dentistry and Periodontology, Trinity College Dublin, Dublin Dental University Hospital, Dublin, Ireland
| | - Yukako Yamauchi
- Division of Restorative Dentistry and Periodontology, Trinity College Dublin, Dublin Dental University Hospital, Dublin, Ireland
| | - Brenda P F A Gomes
- Department of Restorative Dentistry, Division of Endodontics, Piracicaba Dental School, State University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil
| | - Henry F Duncan
- Division of Restorative Dentistry and Periodontology, Trinity College Dublin, Dublin Dental University Hospital, Dublin, Ireland
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Kulthanaamondhita P, Kornsuthisopon C, Chansaenroj A, Suwittayarak R, Trachoo V, Manokawinchoke J, Lee SC, Egusa H, Kim JM, Osathanon T. Notch signaling regulates mineralization via microRNA modulation in dental pulp stem cells. Oral Dis 2024; 30:4547-4557. [PMID: 38243590 DOI: 10.1111/odi.14868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Revised: 12/01/2023] [Accepted: 01/03/2024] [Indexed: 01/21/2024]
Abstract
OBJECTIVES This study investigated the miRNA expression profile in Notch-activated human dental stem pulp stem cells (DPSCs) and validated the functions of miRNAs in modulating the odonto/osteogenic properties of DPSCs. METHODS DPSCs were treated with indirect immobilized Jagged1. The miRNA expression profile was examined using NanoString analysis. Bioinformatic analysis was performed, and miRNA expression was validated. Odonto/osteogenic differentiation was examined using alkaline phosphatase staining, Alizarin Red S staining, as well as odonto/osteogenic-related gene and protein expression. RESULTS Fourteen miRNAs were differentially expressed in Jagged1-treated DPSCs. Pathway analysis revealed that altered miRNAs were associated with TGF-β, Hippo, ErbB signalling pathways, FoxO and Ras signalling. Target prediction analysis demonstrated that 7604 genes were predicted to be targets for these altered miRNAs. Enrichment analysis revealed relationships to various DNA bindings. Among differentially expressed miRNA, miR-296-3p and miR-450b-5p were upregulated under Jagged1-treated conditions. Overexpression of miR-296-3p and miR-450b-5p enhanced mineralization and upregulation of odonto/osteogenic-related genes, whereas inhibition of these miRNAs revealed opposing results. The miR-296-3p and miR-450b-5p inhibitors attenuated the effects of Jagged1-induced mineralization in DPSCs. CONCLUSIONS Jagged-1 promotes mineralization in DPSCs that are partially regulated by miRNA. The novel understanding of these miRNAs could lead to innovative controlled mechanisms that can be applied to modulate biology-targeted dental materials.
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Affiliation(s)
- Promphakkon Kulthanaamondhita
- Center of Excellence for Dental Stem Cell Biology and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Chatvadee Kornsuthisopon
- Center of Excellence for Dental Stem Cell Biology and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Ajjima Chansaenroj
- Center of Excellence for Dental Stem Cell Biology and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Ravipha Suwittayarak
- Center of Excellence for Dental Stem Cell Biology and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Voraphat Trachoo
- Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Jeeranan Manokawinchoke
- Center of Excellence for Dental Stem Cell Biology and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Seung-Cheol Lee
- Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Hiroshi Egusa
- Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan
| | - Jin Man Kim
- Department of Oral Microbiology and Immunology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea
| | - Thanaphum Osathanon
- Center of Excellence for Dental Stem Cell Biology and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
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Stefańska K, Volponi AA, Kulus M, Waśko J, Farzaneh M, Grzelak J, Azizidoost S, Mozdziak P, Bukowska D, Antosik P, Zabel M, Podhorska-Okołów M, Dzięgiel P, Szcześniak M, Woszczyk M, Kempisty B. Dental pulp stem cells - A basic research and future application in regenerative medicine. Biomed Pharmacother 2024; 178:116990. [PMID: 39024839 DOI: 10.1016/j.biopha.2024.116990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 06/10/2024] [Accepted: 06/15/2024] [Indexed: 07/20/2024] Open
Abstract
Dental pulp is a valuable and accessible source of stem cells (DPSCs) with characteristics similar to mesenchymal stem cells. DPSCs can regenerate a range of tissues and their potential for clinical application in regenerative medicine is promising. DPSCs have been found to express low levels of Class II HLA-DR (MHC) molecules, making them potential candidates for allogeneic transplantation without matching the donor's tissue. Research on the correlation between non-coding RNAs (ncRNAs) and human dental pulp stem cells (DPSCs) provides promising insights into the use of these cells in clinical settings for a wide range of medical conditions. It is possible to use a number of ncRNAs in order to restore the functional role of downregulated ncRNAs that are correlated with osteoblastogenesis, or to suppress the functional role of overexpressed ncRNAs associated with osteoclast differentiation in some cases.
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Affiliation(s)
- Katarzyna Stefańska
- Cellivia 3 S.A., Poznan 60-529, Poland; Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan 60-781, Poland.
| | - Ana Angelova Volponi
- Centre for Craniofacial and Regenerative Biology, Dental Institute, King's College London, London WC2R 2LS, UK.
| | - Magdalena Kulus
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland.
| | | | - Maryam Farzaneh
- Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Joanna Grzelak
- Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw 50-368, Poland.
| | - Shirin Azizidoost
- Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Paul Mozdziak
- Prestage Department of Poultry Sciences, North Carolina State University, Raleigh, NC 27695, USA.
| | - Dorota Bukowska
- Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland.
| | - Paweł Antosik
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland.
| | - Maciej Zabel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw 50-368, Poland; Division of Anatomy and Histology, University of Zielona Góra, Zielona Góra 65-046, Poland.
| | - Marzenna Podhorska-Okołów
- Division of Ultrastructural Research, Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw 50-368, Poland.
| | - Piotr Dzięgiel
- Division of Histology and Embryology, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw 50-368, Poland.
| | - Marta Szcześniak
- Department of Diagnostics, Poznan University of Medical Sciences, Bukowska 70, Poznań 60-812, Poland; Department of Maxillofacial Surgery, Poznan University of Medical Sciences, Przybyszewskiego 49, Poznań 60-355, Poland.
| | | | - Bartosz Kempisty
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, Torun 87-100, Poland; Division of Anatomy, Department of Human Morphology and Embryology, Faculty of Medicine, Wroclaw Medical University, Wroclaw 50-368, Poland; College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC 27695, USA; Center of Assisted Reproduction, Department of Obstetrics and Gynecology, University Hospital and Masaryk University, Brno, Czech Republic
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Noferesti M, Darmiani S, Rastegar H. A 980 nm Diode Laser as an Adjunctive Therapy on the Healing of Apical Periodontitis Following Endodontic Retreatment: A Randomized Controlled Clinical Trial Study. J Lasers Med Sci 2024; 15:e36. [PMID: 39193108 PMCID: PMC11348443 DOI: 10.34172/jlms.2024.36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 06/02/2024] [Indexed: 08/29/2024]
Abstract
Introduction: Apical periodontitis is one of the common dental diseases. Microorganisms are the main reasons for these lesions; irrigations are used to remove them, but because of limited penetration, the rinsing agents may not always kill the microorganisms. Laser irradiation is effective in canal disinfection. The goal of this study was to compare the effect of calcium hydroxide (Ca(OH)2 ) and diode laser on the improvement of apical periodontitis following root canal retreatment (RCR). Methods: Twenty-four teeth of 19 patients with periapical lesions which needed RCR were divided into two groups (Ca(OH)2 and Ca(OH)2+laser irradiation [LI]). In the first session, after gutta-percha removal, cleaning, and shaping, Ca(OH)2 was used for 10 days. In the second session, in the Ca(OH)2+LI group, the irradiation utilizing a diode laser (using non-initiated 200-µm fiber, continuous wave (CW), power output of 1W) was done. The periapical radiographic healing was assessed before the retreatment and after 3-month and 6-month follow-ups by periapical index (PAI) Qrstavik. The quantitative data were analyzed (P<0.05). Results: The initial periapical lesion score was 3.75 and 3.88 in the Ca(OH)2 and Ca(OH)2+LI groups, respectively. In the Ca(OH)2 and Ca(OH)2+LI groups, 3 months after the RCR, the average periapical lesion score was 2.94 and 3.05, respectively. In the Ca(OH)2 and CA(OH)2+LI groups, 6 months after the RCR, the average periapical lesion score was 1.80 and 1.75, respectively. No significant differences were found at the 3 and 6 months between the experimental groups. Conclusion: The diode laser can reduce the periapical lesion, but there was no significant difference between CA(OH)2+LI and Ca(OH)2 at 3-month and 6-month follow-ups.
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Affiliation(s)
| | - Soheila Darmiani
- Department of Endodontics, Faculty of Dentistry, Birjand University of Medical Sciences, Birjand, Iran
| | - Homa Rastegar
- Oral & Maxillofacial Radiology Department of Oral and Maxillofacial Radiology, School of Dentistry, Birjand University of Medical Sciences, Birjand, Iran
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Bhat R, Shetty S, Rai P, Kumar BK, Shetty P. Revolutionizing the diagnosis of irreversible pulpitis - Current strategies and future directions. J Oral Biosci 2024; 66:272-280. [PMID: 38508491 DOI: 10.1016/j.job.2024.03.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Revised: 03/08/2024] [Accepted: 03/11/2024] [Indexed: 03/22/2024]
Abstract
BACKGROUND Pulpitis primarily arises from the pulp space infection by oral microbiota. Vital pulp therapy is a minimally invasive approach that relies on assessing the severity of pulpal inflammation to facilitate repair. However, the current evaluation methods prescribed by the American Association of Endodontics are subjective, leading to ambiguity in assessment. Therefore, this review aims to explore molecular strategies for evaluating the severity of pulpal inflammation to accurately predict the success of pulp vitality preservation in clinical settings. METHODOLOGY This review was conducted by searching relevant keywords, such as irreversible pulpitis, pulpitis biomarkers, molecular diagnosis, inflammation, and genomic strategies, in databases such as PubMed, Web of Science, and Scopus to address the subjective nature of diagnosis. The data included in this review were collected up to April 2023. The literature search revealed well-documented limitations in clinically assessing the pulp inflammatory. Molecular approaches that aid in clinical differentiation between irreversible and reversible pulpitis may potentially enhance favorable outcomes in vital pulp therapy. Non-invasive diagnostic methods for pulpal assessment would also be valuable for determining whether the inflamed pulp is reversible, irreversible, or necrotic. CONCLUSION The present review examines the various molecular diagnostic approaches that have revolutionized the medical field and are considered the most promising empirical methodologies for the proactive detection of pulpal diseases. It also provides comprehensive insights into the current diagnostic methods, associated challenges, next-generation strategies, and future directions for diagnosing the severity of pulp inflammation.
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Affiliation(s)
- Raksha Bhat
- Nitte (Deemed to be University), Department of Conservative Dentistry & Endodontics, AB Shetty Memorial Institute of Dental Sciences (ABSMIDS), Mangalore, 575018, Karnataka, India.
| | - Shishir Shetty
- Nitte (Deemed to be University), Department of Conservative Dentistry & Endodontics, AB Shetty Memorial Institute of Dental Sciences (ABSMIDS), Mangalore, 575018, Karnataka, India.
| | - Praveen Rai
- Nitte (Deemed to be University), Department of Infectious Diseases and Microbial Genomics, Nitte University Centre for Science Education and Research (NUCSER), Mangalore, 575018, Karnataka, India.
| | - Ballamoole Krishna Kumar
- Nitte (Deemed to be University), Department of Infectious Diseases and Microbial Genomics, Nitte University Centre for Science Education and Research (NUCSER), Mangalore, 575018, Karnataka, India.
| | - Preethesh Shetty
- Nitte (Deemed to be University), Department of Conservative Dentistry & Endodontics, AB Shetty Memorial Institute of Dental Sciences (ABSMIDS), Mangalore, 575018, Karnataka, India.
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Huang L, Chen X, Yang X, Zhang Y, Liang Y, Qiu X. Elucidating epigenetic mechanisms governing odontogenic differentiation in dental pulp stem cells: an in-depth exploration. Front Cell Dev Biol 2024; 12:1394582. [PMID: 38863943 PMCID: PMC11165363 DOI: 10.3389/fcell.2024.1394582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 05/13/2024] [Indexed: 06/13/2024] Open
Abstract
Epigenetics refers to the mechanisms such as DNA methylation and histone modification that influence gene expression without altering the DNA sequence. These epigenetic modifications can regulate gene transcription, splicing, and stability, thereby impacting cell differentiation, development, and disease occurrence. The formation of dentin is intrinsically linked to the odontogenic differentiation of dental pulp stem cells (DPSCs), which are recognized as the optimal cell source for dentin-pulp regeneration due to their varied odontogenic potential, strong proliferative and angiogenic characteristics, and ready accessibility Numerous studies have demonstrated the critical role of epigenetic regulation in DPSCs differentiation into specific cell types. This review thus provides a comprehensive review of the mechanisms by which epigenetic regulation controls the odontogenesis fate of DPSCs.
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Affiliation(s)
| | | | | | | | | | - Xiaoling Qiu
- Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, China
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11
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Meng T, Liu X, Zhang J, Li S, He W, Li W. MicroRNA-181b attenuates lipopolysaccharide-induced inflammatory responses in pulpitis via the PLAU/AKT/NF-κB axis. Int Immunopharmacol 2024; 127:111451. [PMID: 38154211 DOI: 10.1016/j.intimp.2023.111451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Revised: 12/17/2023] [Accepted: 12/23/2023] [Indexed: 12/30/2023]
Abstract
OBJECTIVE This study aimed to investigate the role and underlying mechanisms of microRNA (miRNA)-181b in the inflammatory response in pulpitis. METHODS Quantitative reverse-transcription polymerase chain reaction (qRT-PCR), fluorescence in situ hybridization (FISH), and immunofluorescence techniques were used to determine the miRNA-181b and urokinase-type plasminogen activator (PLAU) expression levels in inflamed human dental pulp tissues (HDPTs) and lipopolysaccharide (LPS)-stimulated human dental pulp cells (hDPCs). The targets of miRNA-181b were identified and confirmed using a bioinformatics analysis, RNA sequencing, and dual-luciferase gene reporter assays. The effect of miRNA-181b or PLAU on proinflammatory cytokine expression in hDPCs was examined using qRT-PCR and western blotting. RNA sequencing was conducted to examine the signaling pathways implicated in miRNA-181b-mediated pulpitis. Western blotting and qRT-PCR were used to determine the miRNA-181b /PLAU/AKT/NF-κB signaling axis in pulpitis. A rat pulpitis model was created to observe the histopathological changes in the dental pulp tissue after the topical application of miRNA-181b agomir. RESULTS A significant decrease in miRNA-181b and an increase in PLAU were observed in HDPTs compared to the healthy controls, and these two factors showed a negative correlation. MiRNA-181b directly targeted PLAU. The miRNA-181b inhibitor resulted in a significant upregulation of IL-1β, IL-6 and TNF-α, whereas the knockdown of PLAU reversed this proinflammatory effect. Conversely, PLAU overexpression prevented the anti-inflammatory effects of the miRNA-181b mimics. Mechanistically, miRNA-181b inhibited the AKT/NF-κB pathway by targeting PLAU. In vivo application of the miRNA-181b agomir to inflamed pulp tissue alleviated inflammation. CONCLUSION MiRNA-181b targets PLAU, negatively regulating pro-inflammatory cytokine expression via the AKT/NF-κB signaling pathway.
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Affiliation(s)
- Tiantian Meng
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, 69# Mei Shan Road, Hefei 230032, Anhui, China.
| | - Xinpai Liu
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, 69# Mei Shan Road, Hefei 230032, Anhui, China.
| | - Jing Zhang
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, 69# Mei Shan Road, Hefei 230032, Anhui, China.
| | - Song Li
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, 69# Mei Shan Road, Hefei 230032, Anhui, China.
| | - Wei He
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, 69# Mei Shan Road, Hefei 230032, Anhui, China; School of Basic Medical Sciences, Anhui Medical University, 81#Mei Shan Road, Hefei 230032, Anhui, China.
| | - Wuli Li
- College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, 69# Mei Shan Road, Hefei 230032, Anhui, China.
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12
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Luo C, He J, Wang N, Zhu N, Zhang L, Wang Y, Qin M, Hui T. Enhanced reparatory effect of EI1 on dental pulp via extracellular matrix remodeling by miR-181b-2-3p inhibitor. J Dent Sci 2024; 19:177-185. [PMID: 38303812 PMCID: PMC10829547 DOI: 10.1016/j.jds.2023.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 05/02/2023] [Indexed: 02/03/2024] Open
Abstract
Background/purpose Extracellular matrix (ECM) is crucial for dental pulp repair. The aim of this paper is to investigate the ECM remodeling effect of miR-181b-2-3p (a microRNA) and to verify the reparatory effect of EI1 (an epigenetic drug) and miR-181b-2-3p inhibitor on dental pulp. Materials and methods Levels of ECM-related factors in EI1-treated human dental pulp cells (hDPCs) were measured by qRT-PCR and Western blot. The anti-inflammation effect of EI1 was examined in Lipopolysaccharide-stimulated hDPCs. miR-181b-2-3p mimics or inhibitors were transfected into hDPCs and then the cells' functions were detected. A dual luciferase reporter assay was used to identify the targets of miR-181b-2-3p. Pulpotomy using miR-181b-2-3p antagomirs and EI1 as pulp capping materials was performed in male six-week-old Sprague-Dawley rats. Results EI1 upregulated ECM-related genes expression in hDPCs, but failed to upregulate the collagen1A1 (COL1A1) protein level. Pro-inflammatory factors were downregulated by EI1 in Lipopolysaccharide-stimulated hDPCs. Overexpression of miR-181b-2-3p downregulated the expression of transforming growth factor-β2 (TGF-β2) and fibronectin type III domain-containing protein 5 precursor (FNDC5), while the inhibition had the opposite effect. Dual luciferase reporter assays demonstrated that miR-181b-2-3p targets TGF-β2, FNDC5 and integrin alpha 4 protein (ITGA4). Compared to EI1 was used alone, EI1 combined with the inhibitor upregulated the protein levels of COL1A1, fibronectin (FN1) and TGF-β2 in hDPCs, promoted hDPCs migration, and exhibited reparatory effects on inflamed rat pulp tissue. Conclusion miR-181b-2-3p inhibitor could enhance the reparatory effect of EI1 via ECM remodeling in dental pulp both in vitro and in vivo.
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Affiliation(s)
- Chiyi Luo
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
| | - Jie He
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
- Shenzhen Children's Hospital, Shenzhen, China
| | - Nan Wang
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
| | - Ningxin Zhu
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
| | - Lixin Zhang
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
| | - Yuanyuan Wang
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
| | - Man Qin
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
| | - Tianqian Hui
- Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology, Beijing, China
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13
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Nasiri K, Jahri M, Kolahdouz S, Soleimani M, Makiya A, Saini RS, Merza MS, Yasamineh S, Banakar M, Yazdanpanah MH. MicroRNAs Function in Dental Stem Cells as a Promising Biomarker and Therapeutic Target for Dental Diseases. Mol Diagn Ther 2023; 27:703-722. [PMID: 37773247 DOI: 10.1007/s40291-023-00675-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/23/2023] [Indexed: 10/01/2023]
Abstract
Undifferentiated, highly proliferative, clonogenic, and self-renewing dental stem cells have paved the way for novel approaches to mending cleft palates, rebuilding lost jawbone and periodontal tissue, and, most significantly, recreating lost teeth. New treatment techniques may be guided by a better understanding of these cells and their potential in terms of the specificity of the regenerative response. MicroRNAs have been recognized as an essential component in stem cell biology due to their role as epigenetic regulators of the processes that determine stem cell destiny. MicroRNAs have been proven to be crucial in a wide variety of molecular and biological processes, including apoptosis, cell proliferation, migration, and necrocytosis. MicroRNAs have been recognized to control protein translation, messenger RNA stability, and transcription and have been reported to play essential roles in dental stem cell biology, including the differentiation of dental stem cells, the immunological response, apoptosis, and the inflammation of the dental pulp. Because microRNAs increase dental stem cell differentiation, they may be used in regenerative medicine to either preserve the stem cell phenotype or to aid in the development of tooth tissue. The development of novel biomarkers and therapies for dental illnesses relies heavily on progress made in our knowledge of the roles played by microRNAs in regulating dental stem cells. In this article, we discuss how dental stem cells and their associated microRNAs may be used to cure dental illness.
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Affiliation(s)
- Kamyar Nasiri
- Department of Dentistry, Islamic Azad University, Tehran, Iran
| | - Mohammad Jahri
- Dental Research Center, School of Dentistry, Shahid Beheshti, Research Institute of Dental Sciences, University of Medical Sciences, Tehran, Iran
| | | | | | - Ali Makiya
- Student Research Committee, Faculty of Dentistry, Mashhad University of Medical Science, Mashhad, Iran
| | - Ravinder S Saini
- COAMS, King Khalid University, Abha, 62529, Kingdom of Saudi Arabia
| | - Muna S Merza
- Prosthetic Dental Techniques Department, Al-Mustaqbal University College, Babylon, 51001, Iraq
| | - Saman Yasamineh
- Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Morteza Banakar
- Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
- Department of Pediatric Dentistry, Faculty of Dentistry, Shahed University, Tehran, Iran.
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Karrar RN, Cushley S, Duncan HF, Lundy FT, Abushouk SA, Clarke M, El-Karim IA. Molecular biomarkers for objective assessment of symptomatic pulpitis: A systematic review and meta-analysis. Int Endod J 2023; 56:1160-1177. [PMID: 37392154 DOI: 10.1111/iej.13950] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 05/23/2023] [Accepted: 06/22/2023] [Indexed: 07/03/2023]
Abstract
BACKGROUND Inflammatory biomarkers are potentially useful targets for pulpal diagnostic tests that can identify pulp status and predict vital pulp treatment (VPT) outcome, however, their accuracy is unknown. OBJECTIVES (1) Calculate sensitivity, specificity and diagnostic odds ratio (DOR) of previously investigated pulpitic biomarkers; (2) Determine if biomarker levels discriminate between clinical diagnoses of pulpitis based on the presence or absence of spontaneous pain (3) Evaluate if biomarker level can predict VPT outcome. METHODS Searches: PubMed/MEDLINE, Ovid SP, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, Embase, Web of Science and Scopus in May 2023. INCLUSION prospective and retrospective observational studies and randomized trials. Participants were humans with vital permanent teeth and a well-defined pulpal diagnosis. EXCLUSION deciduous teeth, in vitro and animal studies. Risk of bias was assessed with modified-Downs and Black quality assessment checklist. Meta-analysis was performed using bivariate random effect model in Meta-DiSc 2.0 and RevMan and the quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. RESULTS Fifty-six studies were selected, reporting >70 individual biomolecules investigating pulpal health and disease at the gene and protein level. Most studies were of low and fair quality. Among the biomolecules investigated, IL-8 and IL-6 demonstrated a level of diagnostic accuracy with high sensitivity, specificity and DOR to discriminate between healthy pulps and those exhibiting spontaneous pain suggestive of IRP (low-certainty evidence). However, none was shown to have high DOR and the ability to discriminate between pulpitic states (very low certainty evidence). Limited data suggests high levels of matrix metalloproteinase 9 correlate with poorer outcomes of full pulpotomy. DISCUSSION The inability of identified molecular inflammatory markers to discriminate between dental pulps with spontaneous and non-spontaneous pain should shift the focus to improved study quality or the pursuit of other molecules potentially associated with healing and repair. CONCLUSIONS Low-quality evidence suggests IL-8 and IL-6 demonstrated level of diagnostic accuracy to discriminate between healthy pulps and those exhibiting spontaneous pain. There is a need for standardized biomarker diagnostic and prognostic studies focusing on solutions that can accurately determine the degree of pulp inflammation. REGISTRATION PROSPERO CRD42021259305.
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Affiliation(s)
- Riham N Karrar
- Faculty of Dentistry, University of Khartoum, Khartoum, Sudan
| | - Siobhan Cushley
- School of Medicine Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK
| | - Henry F Duncan
- Division of Restorative Dentistry & Periodontology, Dublin Dental University Hospital, Trinity College Dublin, University of Dublin, Dublin, Ireland
| | - Fionnuala T Lundy
- School of Medicine Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK
| | | | - Mike Clarke
- School of Medicine Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK
| | - Ikhlas A El-Karim
- School of Medicine Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK
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15
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Palideh A, Vaghari-Tabari M, Nosrati Andevari A, Qujeq D, Asemi Z, Alemi F, Rouhani Otaghsara H, Rafieyan S, Yousefi B. MicroRNAs and Periodontal Disease: Helpful Therapeutic Targets? Adv Pharm Bull 2023; 13:423-434. [PMID: 37646047 PMCID: PMC10460817 DOI: 10.34172/apb.2023.048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 05/07/2022] [Accepted: 07/01/2022] [Indexed: 09/01/2023] Open
Abstract
Periodontal disease is the most common oral disease. This disease can be considered as an inflammatory disease. The immune response to bacteria accumulated in the gum line plays a key role in the pathogenesis of periodontal disease. In addition to immune cells, periodontal ligament cells and gingival epithelial cells are also involved in the pathogenesis of this disease. miRNAs which are small RNA molecules with around 22 nucleotides have a considerable relationship with the immune system affecting a wide range of immunological events. These small molecules are also in relation with periodontium tissues especially periodontal ligament cells. Extensive studies have been performed in recent years on the role of miRNAs in the pathogenesis of periodontal disease. In this review paper, we have reviewed the results of these studies and discussed the role of miRNAs in the immunopathogenesis of periodontal disease comprehensively. miRNAs play an important role in the pathogenesis of periodontal disease and maybe helpful therapeutic targets for the treatment of periodontal disease.
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Affiliation(s)
| | - Mostafa Vaghari-Tabari
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Nosrati Andevari
- Department of Biochemistry, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Durdi Qujeq
- Cellular and Molecular Biology Research Center (CMBRC), Health Research Institute, Babol University of Medical Sciences, Babol, Iran
- Department of Clinical Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Forough Alemi
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Sona Rafieyan
- Department of Oral and Maxillofacial Pathology, School of Dentistry, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Bahman Yousefi
- Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Han P, Sunada-Nara K, Kawashima N, Fujii M, Wang S, Kieu TQ, Yu Z, Okiji T. MicroRNA-146b-5p Suppresses Pro-Inflammatory Mediator Synthesis via Targeting TRAF6, IRAK1, and RELA in Lipopolysaccharide-Stimulated Human Dental Pulp Cells. Int J Mol Sci 2023; 24:7433. [PMID: 37108595 PMCID: PMC10138803 DOI: 10.3390/ijms24087433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/07/2023] [Accepted: 04/15/2023] [Indexed: 04/29/2023] Open
Abstract
MicroRNA-146b-5p (miR-146b-5p) is up-regulated during and to suppress the inflammation process, although mechanisms involved in the action of miR-146b-5p have not been fully elucidated. This study examined the anti-inflammation effects of miR-146b-5p in lipopolysaccharide (LPS)-stimulated human dental pulp cells (hDPCs). An increase in human miR-146b-5p (hsa-miR-146b-5p) expression following the mRNA expression of pro-inflammatory cytokines was observed in LPS-stimulated hDPCs. The expression of hsa-miR-146b-5p and pro-inflammatory cytokines was down-regulated by a nuclear factor-kappa B (NF-κB) inhibitor, and the expression of hsa-miR-146b-5p was also decreased by a JAK1/2 inhibitor. Enforced expression of hsa-miR-146b-5p abolished phosphorylation of NF-κB p65 and down-regulated the expression of pro-inflammatory cytokines and NF-κB signaling components, such as interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), and REL-associated protein involved in NF-κB (RELA). Expression of rat miR-146b-5p (rno-miR-146b-5p) and pro-inflammatory cytokine mRNA was also up-regulated in experimentally-induced rat pulpal inflammation in vivo, and rno-miR-146b-5p blocked the mRNA expression of pro-inflammatory mediators and NF-κB signaling components in LPS-stimulated ex vivo cultured rat incisor pulp tissues. These findings suggest that the synthesis of miR-146b-5p is controlled via an NF-κB/IL6/STAT3 signaling cascade, and in turn, miR-146b-5p down-regulates the expression of pro-inflammatory mediators by targeting TRAF6, IRAK1, and RELA in LPS-stimulated hDPCs.
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Affiliation(s)
| | - Keisuke Sunada-Nara
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan; (P.H.); (M.F.); (S.W.); (T.Q.K.); (Z.Y.); (T.O.)
| | - Nobuyuki Kawashima
- Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan; (P.H.); (M.F.); (S.W.); (T.Q.K.); (Z.Y.); (T.O.)
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17
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Fujii Y, Hatori A, Chikazu D, Ogasawara T. Application of Dental Pulp Stem Cells for Bone and Neural Tissue Regeneration in Oral and Maxillofacial Region. Stem Cells Int 2023; 2023:2026572. [PMID: 37035445 PMCID: PMC10076122 DOI: 10.1155/2023/2026572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 10/21/2022] [Accepted: 03/18/2023] [Indexed: 03/31/2023] Open
Abstract
In the oral and maxillofacial region, the treatment of severe bone defects, caused by fractures, cancers, congenital abnormalities, etc., remains a great challenge. In addition, neurological disorders are frequently accompanied by these bone defects or the treatments for them. Therefore, novel bone regenerative techniques and methods to repair nerve injury are eagerly sought. Among them, strategies using dental pulp stem cells (DPSCs) are promising options. Human DPSCs can be collected easily from extracted teeth and are now considered a type of mesenchymal stem cell with higher clonogenic and proliferative potential. DPSCs have been getting attention as a cell source for bone and nerve regeneration. In this article, we reviewed the latest studies on osteogenic or neural differentiation of DPSCs as well as bone or neural regeneration methods using DPSCs and discussed the potential of DPSCs for bone and nerve tissue regeneration.
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18
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The paradigm of miRNA and siRNA influence in Oral-biome. Biomed Pharmacother 2023; 159:114269. [PMID: 36682246 DOI: 10.1016/j.biopha.2023.114269] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 01/12/2023] [Accepted: 01/16/2023] [Indexed: 01/22/2023] Open
Abstract
Short nucleotide sequences like miRNA and siRNA have attracted a lot of interest in Oral-biome investigations. miRNA is a small class of non-coding RNA that regulates gene expression to provide effective regulation of post-transcription. On contrary, siRNA is 21-25 nucleotide dsRNA impairing gene function post-transcriptionally through inhibition of mRNA for homologous dependent gene silencing. This review highlights the application of miRNA in oral biome including oral cancer, dental implants, periodontal diseases, gingival fibroblasts, oral submucous fibrosis, radiation-induced oral mucositis, dental Pulp, and oral lichenoid disease. Moreover, we have also discussed the application of siRNA against the aforementioned disease along with the impact of miRNA and siRNA to the various pathways and molecular effectors pertaining to the dental diseases. The influence of upregulation and downregulation of molecular effector post-treatment with miRNA and siRNA and their impact on the clinical setting has been elucidated. Thus, the mentioned details on application of miRNA and siRNA will provide a novel gateway to the scholars to not only mitigate the long-lasting issue in dentistry but also develop new theragnostic approaches.
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Al Gashaamy ZJ, Alomar T, Al-Sinjary L, Wazzan M, Saeed MH, Al-Rawi NH. MicroRNA expression in apical periodontitis and pulpal inflammation: a systematic review. PeerJ 2023; 11:e14949. [PMID: 36890871 PMCID: PMC9987318 DOI: 10.7717/peerj.14949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 02/02/2023] [Indexed: 03/06/2023] Open
Abstract
Background The aim of this systematic review is to determine microRNAs (miRs) that are differently expressed between diseased pulpal and periapical tissues. Design This systematic review used PubMed, Scopus, EBSCO, ProQuest, Cochrane database as well as manual searching to extract studies from January 2012 up to February 2022. Results A total of 12 studies met the eligibility criteria were included. All selected studies were of case-control type. Twenty-four miRNAs associated with apical periodontitis, 11 were found to be upregulatedand 13 were downregulated. Four out of the 44 miRs associated with pulpal inflammation were upregulated, whereas forty were downregulated. Six miRs, namely hsa-miR-181b, hsa-miR-181c,hsa-miR-455-3p,hsa-miR-128-3p, hsa-miR199a-5p, and hsa-miR-95, exhibited considerable downregulation in both periapical and pulp tissues. Conclusion MiRs have been investigated for their role in pulpal and periapical biology and may be utilised in diagnostic and therapeutic purposes. Further investigations are required to determine why certain irreversible pulpitis situations progress to apical periodontitis and others do not, based on the various miR expressions. Moreover, clinical and laboratory trials are needed to support this theory.
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Affiliation(s)
- Zainab Jamal Al Gashaamy
- Oral & Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Tiba Alomar
- Oral & Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Linah Al-Sinjary
- Oral & Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Mohammad Wazzan
- Oral & Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Musab Hamed Saeed
- Department of Clinical Science, College of Dentistry, Ajman University, Ajman, United Arab Emirates.,Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Natheer H Al-Rawi
- Oral & Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
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20
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Exploring craniofacial and dental development with microRNAs. Biochem Soc Trans 2022; 50:1897-1909. [DOI: 10.1042/bst20221042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/16/2022] [Accepted: 11/17/2022] [Indexed: 12/14/2022]
Abstract
microRNAs (miRs) are small RNA molecules that regulate many cellular and developmental processes. They control gene expression pathways during specific developmental time points and are required for tissue homeostasis and stem cell maintenance. miRs as therapeutic reagents in tissue regeneration and repair hold great promise and new technologies are currently being designed to facilitate their expression or inhibition. Due to the large amount of miR research in cells and cancer many cellular processes and gene networks have been delineated however, their in vivo response can be different in complex tissues and organs. Specifically, this report will discuss animal developmental models to understand the role of miRs as well as xenograft, disease, and injury models. We will discuss the role of miRs in clinical studies including their diagnostic function, as well as their potential ability to correct craniofacial diseases.
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21
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MicroRNA and their implications in dental pulp inflammation: current trends and future perspectives. Odontology 2022:10.1007/s10266-022-00762-0. [DOI: 10.1007/s10266-022-00762-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 10/18/2022] [Indexed: 11/25/2022]
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22
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Li J, Wang Z. A novel NUTM2A-AS1/miR-769–5p axis regulates LPS-evoked damage in human dental pulp cells via the TLR4/MYD88/NF-κB signaling. J Dent Sci 2022. [DOI: 10.1016/j.jds.2022.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
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Jiang L, Krongbaramee T, Lin X, Zhu M, Zhu Y, Hong L. microRNA-126 inhibits vascular cell adhesion molecule-1 and interleukin-1beta in human dental pulp cells. J Clin Lab Anal 2022; 36:e24371. [PMID: 35334501 PMCID: PMC9102615 DOI: 10.1002/jcla.24371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 02/21/2022] [Accepted: 03/15/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Vascular cell adhesion molecule (VCAM-1) mediates pulpitis via regulating interleukin (IL)-1β. microRNA (miR)-126 was reported to regulate the VCAM-1 under many different pathophysiological circumstances. We investigated variations of miR-126 and VCAM-1 in inflamed patient pulp tissues and determined potential roles of miR-126 in pulpitis using human dental pulp cells (hDPCs) in vitro. METHODS We quantitatively measured the transcripts of miR-126 and VCAM-1 in inflamed human pulp tissues using qRT-PCR and compared with those from healthy human pulp tissues. In addition, we transfected miR-126 in hDPCs using plasmid DNA (pDNA)-encoding miR-126 delivered by polyethylenimine (PEI) nanoparticles. RESULTS The irreversible pulpitis significantly reduced miR-126 and increased the transcript of VCAM-1 in pulp tissues (p < 0.05). pDNA-encoding miR-126 delivered PEI nanoparticles and effectively upregulated the expression of miR-126 in hDPCs (p < 0.05). The overexpression of miR-126 could effectively suppress the transcripts and protein levels of VCAM-1 and IL-1β induced by Pg-LPS at 100ng/mL in DPCs (p < 0.05). CONCLUSIONS miR-126 is involved in pulpitis and downregulated the VCAM-1 and IL-1β in DPCs. miR-126 may be a potential target to attenuate the inflammation of pulpitis.
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Affiliation(s)
- Long Jiang
- Department of General DentistryShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghaiChina
- Iowa Institute for Oral Health ResearchCollege of DentistryThe University of IowaIowa CityIowaUSA
| | - Tadkamol Krongbaramee
- Iowa Institute for Oral Health ResearchCollege of DentistryThe University of IowaIowa CityIowaUSA
| | - Xinhai Lin
- Department of General DentistryShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghaiChina
| | - Min Zhu
- Iowa Institute for Oral Health ResearchCollege of DentistryThe University of IowaIowa CityIowaUSA
| | - Yaqin Zhu
- Department of General DentistryShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghaiChina
| | - Liu Hong
- Iowa Institute for Oral Health ResearchCollege of DentistryThe University of IowaIowa CityIowaUSA
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Kulthanaamondhita P, Kornsuthisopon C, Photichailert S, Manokawinchoke J, Limraksasin P, Osathanon T. Specific microRNAs regulate dental pulp stem cell behavior. J Endod 2022; 48:688-698. [PMID: 35271859 DOI: 10.1016/j.joen.2022.02.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 02/10/2022] [Accepted: 02/25/2022] [Indexed: 02/07/2023]
Abstract
INTRODUCTION MicroRNAs (miRNAs), small non-coding RNA, control the translation of messenger RNAs into proteins. miRNAs have a crucial role in regulating the diverse biological processes of many physiological and pathological activities. The aim of this systematic review is to explore various functions of miRNAs in the regulation of dental pulp stem cells (DPSCs) behavior. METHODS The articles were searched in PubMed, SCOPUS and ISI Web of Science database using designated keywords. Full-length manuscripts published in English in peer-reviewed journals relevant to the role of miRNAs in DPSC functions were included and reviewed by 2 independent researchers. RESULTS The original search of the database generated 299 studies. One hundred and two duplicate studies were removed. After their exclusion, 48 studies were selected for review. miRNAs have shown to modulate the stemness and differentiation of various mesenchymal stem cells. The miRNAs expression profiles in DPSCs were differed compared with other cell types and have been demonstrated to regulate the levels of proteins crucial for promoting or inhibiting DPSC proliferation as well as differentiation. Further, miRNAs also modulate inflammatory processes in dental pulp. CONCLUSION miRNAs have various function upon the regulation of DPSCs and understanding these roles of miRNAs is crucial for the development of new therapeutics in regenerative dental medicine. With the advancing technologies, the utilization of miRNA technology could revolutionarily change the future of regenerative endodontics.
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Affiliation(s)
- Promphakkon Kulthanaamondhita
- Dental Stem Cell Biology Research Unit and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Chatvadee Kornsuthisopon
- Dental Stem Cell Biology Research Unit and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Suphalak Photichailert
- Dental Stem Cell Biology Research Unit and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Jeeranan Manokawinchoke
- Dental Stem Cell Biology Research Unit and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Phoonsuk Limraksasin
- Dental Stem Cell Biology Research Unit and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand; Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan
| | - Thanaphum Osathanon
- Dental Stem Cell Biology Research Unit and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
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Valverde A, Seal A, Nares S, Shukla D, Naqvi AR. Human herpesvirus-encoded MicroRNA in host-pathogen interaction. Adv Biol Regul 2021; 82:100829. [PMID: 34560402 PMCID: PMC11646283 DOI: 10.1016/j.jbior.2021.100829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/28/2021] [Accepted: 09/13/2021] [Indexed: 11/17/2022]
Abstract
Human herpesviruses (HHV) are ubiquitous, linear dsDNA viruses that establish lifelong latency, disrupted by sporadic reactivation. HHV have evolved diverse ingenious mechanisms to evade robust host defenses. Incorporation of unique stem loop sequences that generate viral microRNAs (v-miRs) exemplifies one such evolutionary adaptation in HHV. These noncoding RNAs can control cellular and viral transcriptomes highlighting their ability in shaping host-HHV interactions. We summarize recent developments in functional characterization of HHV-encoded miRNAs in shaping the outcome of host-pathogen interaction. Non-immunogenic dissemination of v-miRs through exosomes confer added advantage to HHV in incessant modulation of host microenvironment. This review delineates the mechanistic role of v-miRs in facilitating viral persistence and tropism by targeting genes associated with cellular (apoptosis, angiogenesis, cell migration, etc.) and viral life cycle (latency, lytic and reactivation). Burgeoning evidences indicate plausible association of v-miRs in various immune-mediated diseases (nasopharyngeal carcinoma, neurological disorders, periodontal diseases, etc.) and herpesvirus-related malignancies indicating their broad-spectrum impact on host cellular pathways. We propose to exploit tisssue and systemic levels of v-miRs as diagnostic and prognostic markers for cancers and immune-mediated diseases. Therapeutic targeting of v-miRs will advance the promising outcomes of preclinical discoveries to bedside application.
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Affiliation(s)
- Araceli Valverde
- Department of Periodontics, College of Dentistry, University of Illinois at Chicago, United States
| | - Alexandra Seal
- Department of Periodontics, College of Dentistry, University of Illinois at Chicago, United States
| | - Salvador Nares
- Department of Periodontics, College of Dentistry, University of Illinois at Chicago, United States
| | - Deepak Shukla
- Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, United States; Department of Ophthalmology and Visual Sciences, University of Illinois Medical Center, Chicago, IL, United States
| | - Afsar Raza Naqvi
- Department of Periodontics, College of Dentistry, University of Illinois at Chicago, United States.
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Liu Y, Gan L, Cui DX, Yu SH, Pan Y, Zheng LW, Wan M. Epigenetic regulation of dental pulp stem cells and its potential in regenerative endodontics. World J Stem Cells 2021; 13:1647-1666. [PMID: 34909116 PMCID: PMC8641018 DOI: 10.4252/wjsc.v13.i11.1647] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 06/07/2021] [Accepted: 11/03/2021] [Indexed: 02/06/2023] Open
Abstract
Regenerative endodontics (RE) therapy means physiologically replacing damaged pulp tissue and regaining functional dentin–pulp complex. Current clinical RE procedures recruit endogenous stem cells from the apical papilla, periodontal tissue, bone marrow and peripheral blood, with or without application of scaffolds and growth factors in the root canal space, resulting in cementum-like and bone-like tissue formation. Without the involvement of dental pulp stem cells (DPSCs), it is unlikely that functional pulp regeneration can be achieved, even though acceptable repair can be acquired. DPSCs, due to their specific odontogenic potential, high proliferation, neurovascular property, and easy accessibility, are considered as the most eligible cell source for dentin–pulp regeneration. The regenerative potential of DPSCs has been demonstrated by recent clinical progress. DPSC transplantation following pulpectomy has successfully reconstructed neurovascularized pulp that simulates the physiological structure of natural pulp. The self-renewal, proliferation, and odontogenic differentiation of DPSCs are under the control of a cascade of transcription factors. Over recent decades, epigenetic modulations implicating histone modifications, DNA methylation, and noncoding (nc)RNAs have manifested as a new layer of gene regulation. These modulations exhibit a profound effect on the cellular activities of DPSCs. In this review, we offer an overview about epigenetic regulation of the fate of DPSCs; in particular, on the proliferation, odontogenic differentiation, angiogenesis, and neurogenesis. We emphasize recent discoveries of epigenetic molecules that can alter DPSC status and promote pulp regeneration through manipulation over epigenetic profiles.
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Affiliation(s)
- Ying Liu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lu Gan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Di-Xin Cui
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Si-Han Yu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yue Pan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Li-Wei Zheng
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Mian Wan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China
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The Role of microRNAs in Pulp Inflammation. Cells 2021; 10:cells10082142. [PMID: 34440911 PMCID: PMC8391605 DOI: 10.3390/cells10082142] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 08/17/2021] [Accepted: 08/17/2021] [Indexed: 02/07/2023] Open
Abstract
The dental pulp can be affected by thermal, physical, chemical, and bacterial phenomena that stimulate the inflammatory response. The pulp tissue produces an immunological, cellular, and vascular reaction in an attempt to defend itself and resolve the affected tissue. The expression of different microRNAs during pulp inflammation has been previously documented. MicroRNAs (miRNAs) are endogenous small molecules involved in the transcription of genes that regulate the immune system and the inflammatory response. They are present in cellular and physiological functions, as well as in the pathogenesis of human diseases, becoming potential biomarkers for diagnosis, prognosis, monitoring, and safety. Previous studies have evidenced the different roles played by miRNAs in proinflammatory, anti-inflammatory, and immunological phenomena in the dental pulp, highlighting specific key functions of pulp pathology. This systematized review aims to provide an understanding of the role of the different microRNAs detected in the pulp and their effects on the expression of the different target genes that are involved during pulp inflammation.
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Liu L, Wang T, Huang D, Song D. Comprehensive Analysis of Differentially Expressed Genes in Clinically Diagnosed Irreversible Pulpitis by Multiplatform Data Integration Using a Robust Rank Aggregation Approach. J Endod 2021; 47:1365-1375. [PMID: 34260959 DOI: 10.1016/j.joen.2021.07.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 05/24/2021] [Accepted: 07/01/2021] [Indexed: 02/05/2023]
Abstract
INTRODUCTION Molecular diagnosis may overcome the limitations of clinical and histologic diagnosis in pulpitis, thereby benefiting many treatment techniques, such as vital pulp therapies. In this study, integrated microarray data on pulpitis were used to obtain a list of normalized differentially expressed (DE) genes for analyzing the molecular mechanisms underlying pulpitis and identifying potential diagnostic biomarkers. METHODS A systematic search of public microarray and sequencing databases was performed to obtain expression data of pulpitis. Robust rank aggregation (RRA) was used to obtain DE gene lists (RRA_DEmRNAs and RRA_DElncRNAs) between inflamed pulp and normal samples. DE genes were evaluated by functional enrichment analyses, correlation analyses for inflammation-related RRA_DEmRNAs, and protein-protein interaction and competing endogenous RNA network construction. Quantitative real-time polymerase chain reaction validation was applied in snap-frozen pulp tissues. RESULTS Using the GSE77459 and GSE92681 data sets, 280 RRA_DEmRNAs and 90 RRA_DElncRNAs were identified. RRA_DEmRNAs were significantly enriched in inflammation-related biological processes and osteoclast differentiation and tumor necrosis factor, chemokine, and B-cell receptor signaling pathways. The molecular complex detection and cytoHubba methods identified 2 clusters and 10 hub genes in the protein-protein interaction network. The competing endogenous RNA network was composed of 2 long noncoding RNAs (ADAMTS9-AS2 and LINC00290), 2 microRNAs (hsa-miR-30a-5p and hsa-miR-128-3p), and 3 messenger RNAs (ABCA1, FBLN5, and SOCS3). The expression between most top inflammation-related RRA_DEmRNAs in pulpitis showed positive correlations. Quantitative real-time polymerase chain reacation validated the expression trends of selected genes, including ITGAX, TREM1, CD86, FCGR2A, ADAMTS9-AS2, LINC00290, hsa-miR-30a-5p, hsa-miR-128-3p, RASGRP3, IL3RA, CCDC178, CRISPLD1, LINC01857, AC007991.2, ARHGEF26-AS1, and AL021408.1. CONCLUSIONS The identified biomarkers provide insight into the pathology and may aid in the molecular diagnosis of pulpitis.
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Affiliation(s)
- Liu Liu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Tianyi Wang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Dingming Huang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Dongzhe Song
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
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Non-coding RNAs in endodontic disease. Semin Cell Dev Biol 2021; 124:82-84. [PMID: 34257038 DOI: 10.1016/j.semcdb.2021.07.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 05/27/2021] [Accepted: 07/04/2021] [Indexed: 12/22/2022]
Abstract
The immunocompetence and regeneration potential of the dental pulp and its surrounding apical tissues have been investigated extensively in the field of endodontics. While research on the role of non-coding RNAs in these tissues is still in its infancy, it is envisioned that improved understanding of the regulatory function of ncRNAs in pulpal and periapical immune response will help prevent or treat endodontic disease. Of particular importance is the role of these RNAs in regenerating the dentin-pulp complex. In this review, we highlight recent progress on the role of non-coding RNAs in the immune response to endodontic infection as well as the repair and regenerative response to injury.
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Wang X, Sun H, Hu Z, Mei P, Wu Y, Zhu M. NUTM2A-AS1 silencing alleviates LPS-induced apoptosis and inflammation in dental pulp cells through targeting let-7c-5p/HMGB1 axis. Int Immunopharmacol 2021; 96:107497. [PMID: 33831808 DOI: 10.1016/j.intimp.2021.107497] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 02/03/2021] [Accepted: 02/08/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND Long non-coding RNA (lncRNA) NUTM2A antisense RNA 1 (NUTM2A-AS1) has been reported to be abnormally up-regulated in pulpitis tissues. However, the function of NUTM2A-AS1 in pulpitis remains unclear. The aim of this study was to investigate the role and working mechanism of NUTM2A-AS1 in pulpitis using lipopolysaccharide (LPS)-treated human dental pulp cells (HDPCs). METHODS 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and lactate dehydrogenase (LDH) release detection assay were conducted to analyze the viability of HDPCs. Cell inflammatory response was analyzed through measuring the protein levels of interleukin-6 (IL-6) and IL-8. Western blot assay and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to measure protein expression and RNA expression, respectively. Bioinformatic database StarBase was used to predict the possible targets of NUTM2A-AS1 and let-7c-5p, and dual-luciferase reporter assay was conducted to verify these intermolecular interactions. RESULTS LPS stimulation restrained cell viability and induced cell apoptosis and inflammation of HDPCs. LPS exposure up-regulated the expression of NUTM2A-AS1 and High-Mobility Group Box 1 (HMGB1) and down-regulated the level of let-7c-5p. LPS-induced injury in HDPCs was partly attenuated by the silencing of NUTM2A-AS1 or HMGB1. Let-7c-5p was confirmed as a direct target of NUTM2A-AS1, and let-7c-5p bound to the 3' untranslated region (3'UTR) of HMGB1 messenger RNA (mRNA) in HDPCs. HMGB1 overexpression largely overturned NUTM2A-AS1 silencing-mediated effects in LPS-induced HDPCs. CONCLUSION NUTM2A-AS1 knockdown attenuated LPS-induced damage in HDPCs partly through targeting let-7c-5p/HMGB1 axis.
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Affiliation(s)
- Xuechun Wang
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Huijun Sun
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Zhekai Hu
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Peng Mei
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Yanqi Wu
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China
| | - Min Zhu
- Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai 200011, China.
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MicroRNA-150 inhibits myeloid-derived suppressor cells proliferation and function through negative regulation of ARG-1 in sepsis. Life Sci 2021; 278:119626. [PMID: 34004247 DOI: 10.1016/j.lfs.2021.119626] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 05/06/2021] [Accepted: 05/10/2021] [Indexed: 01/01/2023]
Abstract
AIMS Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The majority of sepsis-related deaths occur during late sepsis, which presents as a state of immunosuppression. Myeloid-derived suppressor cells (MDSCs) have been reported to promote immunosuppression during sepsis. Here we aim to understand the role of microRNAs in regulating MDSCs proliferation and immunosuppression function during sepsis. MAIN METHODS Murine sepsis model was established using cecal ligation and puncture (CLP). A microarray was used to identify microRNAs with differential expression in murine sepsis. The effect of microRNA-150 on MDSCs proliferation and function was then evaluated. 140 multiple trauma patients from Tongji Hospital and 10 healthy controls were recruited. Peripheral blood samples were taken and the serum level of miR-150 was measured. KEY FINDINGS In the murine model of sepsis, MDSCs expansion was noted in the spleen and bone marrow, while expression of miR-150 in MDSCs decreased. Replenishing miR-150 inhibited the expansion of MDSCs in both monocytic and polymorphonuclear subpopulations, as well as decreasing the immunosuppressive function of MDSCs, through down-regulation of ARG1. Both pro-inflammatory cytokine IL-6 and anti-inflammatory cytokines TGF-β and IL-10 were reduced by miR-150. In human, the serum level of miR-150 was down-regulated in septic patients and elevated in non-septic trauma patients compared to healthy controls. SIGNIFICANCE Our study showed that MiR-150 is down-regulated during sepsis. Replenishing miR-150 reduces the immunosuppression function of MDSCs by down-regulating ARG1 in late sepsis. MiR-150 might serve as a potential therapeutic option for sepsis.
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Shen Z, Silva RM. MicroRNAs: emerging players in apical periodontitis. J Appl Oral Sci 2021; 29:e20201058. [PMID: 33886945 PMCID: PMC8054647 DOI: 10.1590/1678-7757-2020-1058] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 01/20/2021] [Indexed: 12/13/2022] Open
Abstract
Apical periodontitis is an inflammatory disorder of periradicular tissues developed from endodontic infections. Understanding its pathophysiology and the underlying molecular mechanisms is key to the advancement of endodontics. MicroRNAs (miRNAs), a group of evolutionarily conserved small non-coding RNAs, may be phenotypically and functionally associated with the pathogenesis of apical periodontitis. Several studies have focused on the role of miRNAs in the pulp and periradicular biology, and they have demonstrated their essential functions, such as initiating odontogenic differentiation and promoting pro- or anti-inflammatory responses in pulpitis. Up to date, over 2,000 miRNAs have been discovered in humans; however, only few have been reported to associate with apical periodontitis. Therefore, identifying miRNAs involved in diseased apical tissues and conducting functional studies are important in expanding our current knowledge of pulp and periradicular biology and exploring novel therapeutic avenues. In this review, we revisit current models of apical periodontitis and miRNA biogenesis, analyze existing evidence of the involvement of miRNAs in diseased apical tissues, and discuss their diverse functions and potential values. Based on their sheer abundance, prolonged stability in biofluid, and relative ease of sampling, miRNAs may be a useful tool to be developed as diagnostic biomarkers for apical periodontitis. Furthermore, it can be used as therapeutic targets in conjunction with conventional endodontic therapies.
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Affiliation(s)
- Zhen Shen
- The University of Texas Health Science Center at Houston, Department of Endodontics, Houston, TX, United States
| | - Renato Menezes Silva
- The University of Texas Health Science Center at Houston, Department of Endodontics, Houston, TX, United States.,The University of Texas Health Science Center at Houston, Center for Craniofacial Research, Houston, TX, United States
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Xi X, Ma Y, Xu Y, Ogbuehi AC, Liu X, Deng Y, Xi J, Pan H, Lin Q, Li B, Ning W, Jiang X, Li H, Li S, Hu X. The Genetic and Epigenetic Mechanisms Involved in Irreversible Pulp Neural Inflammation. DISEASE MARKERS 2021; 2021:8831948. [PMID: 33777260 PMCID: PMC7968449 DOI: 10.1155/2021/8831948] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 11/02/2020] [Accepted: 01/13/2021] [Indexed: 02/07/2023]
Abstract
AIM To identify the critical genetic and epigenetic biomarkers by constructing the long noncoding RNA- (lncRNA-) related competing endogenous RNA (ceRNA) network involved in irreversible pulp neural inflammation (pulpitis). MATERIALS AND METHODS The public datasets regarding irreversible pulpitis were downloaded from the gene expression omnibus (GEO) database. The differential expression analysis was performed to identify the differentially expressed genes (DEGs) and DElncRNAs. Functional enrichment analysis was performed to explore the biological processes and signaling pathways enriched by DEGs. By performing a weighted gene coexpression network analysis (WGCNA), the significant gene modules in each dataset were identified. Most importantly, DElncRNA-DEmRNA regulatory network and DElncRNA-associated ceRNA network were constructed. A transcription factor- (TF-) DEmRNA network was built to identify the critical TFs involved in pulpitis. RESULT Two datasets (GSE92681 and GSE77459) were selected for analysis. DEGs involved in pulpitis were significantly enriched in seven signaling pathways (i.e., NOD-like receptor (NLR), Toll-like receptor (TLR), NF-kappa B, tumor necrosis factor (TNF), cell adhesion molecules (CAMs), chemokine, and cytokine-cytokine receptor interaction pathways). The ceRNA regulatory relationships were established consisting of three genes (i.e., LCP1, EZH2, and NR4A1), five miRNAs (i.e., miR-340-5p, miR-4731-5p, miR-27a-3p, miR-34a-5p, and miR-766-5p), and three lncRNAs (i.e., XIST, MIR155HG, and LINC00630). Six transcription factors (i.e., GATA2, ETS1, FOXP3, STAT1, FOS, and JUN) were identified to play pivotal roles in pulpitis. CONCLUSION This paper demonstrates the genetic and epigenetic mechanisms of irreversible pulpitis by revealing the ceRNA network. The biomarkers identified could provide research direction for the application of genetically modified stem cells in endodontic regeneration.
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Affiliation(s)
- Xiaoxi Xi
- Department of Stomatology, Northeast Petroleum University Affiliated Hospital, Fazhan Road, High Tech District, 163000 Daqing City, Heilongjiang Province, China
| | - Yihong Ma
- Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
| | - Yuzhen Xu
- Department of Neurology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Middle Yanchang Road, Shanghai, China
| | | | - Xiangqiong Liu
- Laboratory of Molecular Cell Biology, Beijing Tibetan Hospital, China Tibetology Research Center, 218 Anwaixiaoguanbeili Street, Chaoyang, Beijing 100029, China
| | - Yupei Deng
- Laboratory of Molecular Cell Biology, Beijing Tibetan Hospital, China Tibetology Research Center, 218 Anwaixiaoguanbeili Street, Chaoyang, Beijing 100029, China
| | - Junming Xi
- Department of Stomatology, Northeast Petroleum University Affiliated Hospital, Fazhan Road, High Tech District, 163000 Daqing City, Heilongjiang Province, China
| | - Haitong Pan
- Department of Stomatology, Daqing Oilfield General Hospital, Zhongkang Street No. 9, Saertu District, 163000 Daqing City, Heilongjiang Province, China
| | - Qian Lin
- Department of Prosthetics, School of Stomatology, Second Affiliated Dental Hospital of Jiamusi University, Hongqi Street No. 522, Jiamusi City, Heilongjiang Province, China
| | - Bo Li
- Department of Stomatology, South District Hospital, Daqing Oilfield General Hospital Group, Tuqiang Fourth Street No. 14, Hong Gang District, Daqing City, Heilongjiang Province, China
| | - Wanchen Ning
- Department of Conservative Dentistry and Periodontology, Ludwig-Maximilians-University of Munich, Goethestrasse 70, 80336 Munich, Germany
| | - Xiao Jiang
- Stomatological Hospital, Southern Medical University, 510280 Guangzhou, China
| | - Hanluo Li
- Department of Cranio Maxillofacial Surgery, University Clinic Leipzig, Liebigstr. 12, 04103 Leipzig, Germany
| | - Simin Li
- Stomatological Hospital, Southern Medical University, 510280 Guangzhou, China
| | - Xianda Hu
- Laboratory of Molecular Cell Biology, Beijing Tibetan Hospital, China Tibetology Research Center, 218 Anwaixiaoguanbeili Street, Chaoyang, Beijing 100029, China
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Xu N, Cui Y, Dong J, Huang L. Exploring the Molecular Mechanisms of Pterygium by Constructing lncRNA-miRNA-mRNA Regulatory Network. Invest Ophthalmol Vis Sci 2021; 61:12. [PMID: 32645133 PMCID: PMC7425729 DOI: 10.1167/iovs.61.8.12] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Purpose This research explores the aberrant expression of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) in pterygium. A competitive endogenous RNA (ceRNA) network was constructed to elucidate the molecular mechanisms in pterygium. Methods We obtained the differentially expressed mRNAs based on three datasets (GSE2513, GSE51995, and GSE83627), and summarized the differentially expressed miRNAs (DEmiRs) and differentially expressed lncRNAs (DELs) data by published literature. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction (PPI), and gene set enrichment analysis (GSEA) analysis were performed. DEmiRs were verified in GSE21346, and the regulatory network of hub mRNAs, DELs, and DEmiRs were constructed. Results Overall, 40 upregulated and 40 downregulated differentially expressed genes (DEGs) were obtained. The KEGG enrichment showed the DEGs mainly involved in extracellular matrix (ECM)-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway. The GSEA results showed that cornification, keratinization, and cornified envelope were significantly enriched. The validation outcome confirmed six upregulated DEmiRs (miR-766-3p, miR-184, miR-143-3p, miR-138-5p, miR-518b, and miR-1236-3p) and two downregulated DEmiRs (miR-200b-3p and miR-200a-3p). Then, a ceRNA regulatory network was constructed with 22 upregulated and 15 downregulated DEmiRs, 4 downregulated DELs, and 26 upregulated and 33 downregulated DEGs. The network showed that lncRNA SNHG1/miR-766-3p/FOS and some miRNA-mRNA axes were dysregulated in pterygium. Conclusions Our study provides a novel perspective on the regulatory mechanism of pterygium, and lncRNA SNHG1/miR-766-3p/FOS may contribute to pterygium development.
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Zhou M, Li C. Clinical Value and Potential Target of miR-27a-3p in Pulpitis. Neuroimmunomodulation 2021; 28:158-165. [PMID: 34237753 DOI: 10.1159/000516136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 03/23/2021] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION This study investigated the clinical values of miR-27a-3p for pulpitis patients, and its association with TLR4. METHODS Sixty-six patients with pulpitis and 34 cases without pulpitis were recruited; the pulp tissue and serum samples were collected from each participant. Real-time polymerase chain reaction was used for measurement of gene expression levels. The diagnosis values were assessed by the receiver operating characteristic curve. The target gene of miR-27a-3p was confirmed by the luciferase reporter assay. RESULTS MiR-27a-3p was downregulated in both serum and pulp tissue of pulpitis patients. MiR-27a-3p could distinguish pulpitis patients from healthy controls and might be a predictor for the development of irreversible pulpitis. A high level of TLR4 was also detected in both peripheral blood monocytes and pulp tissues from pulpitis patients and showed a negative association with the miR-27a-3p level. TLR4 was a direct target gene of miR-27a-3p. DISCUSSION/CONCLUSION MiR-27a-3p might be a promising biomarker for the diagnosis of pulpitis and predict the development of irreversible pulpitis. MiR-27a-3p might be involved in the pathogenesis of pulpitis via targeting TLR4.
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Affiliation(s)
- Ming Zhou
- Department of Endodontics, Stomatology Hospital of Wuhan University Qingshan Branch, Wuhan, China
| | - Chaohong Li
- Department of Prosthodontics, Stomatology Hospital of Wuhan University, Wuhan, China
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Shen Z, Wichnieski C, Carneiro E, Garlet GP, Letra A, Silva RM. Expression Profiling and Functional Characterization of MicroRNAs in Apical Periodontitis. J Endod 2020; 47:263-271. [PMID: 33245973 DOI: 10.1016/j.joen.2020.11.016] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 11/05/2020] [Accepted: 11/11/2020] [Indexed: 12/11/2022]
Abstract
INTRODUCTION MicroRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs that may orchestrate the pathogenesis of apical periodontitis (AP). This study aimed to identify differentially expressed miRNAs and investigate their target gene pathways in AP. METHODS Total RNA was extracted from 10 human AP and 2 healthy apical tissues (controls) and subjected to miRNA sequencing for the identification of differentially expressed miRNAs (>1.5-fold changes). The function of the most up-regulated miRNA was further studied in vitro. miR-10a-5p mimics and inhibitors were introduced to human stem cells from the apical papilla and K-562 cells challenged with lipopolysaccharide, and expressions of predicted target genes were examined via quantitative reverse-transcription polymerase chain reaction and RNA sequencing. RESULTS A total of 852 miRNAs were identified, of which 12 were significantly up-regulated (1.54- to 8.44-fold) and 94 were significantly down-regulated (0.14- to 0.67-fold) in AP. Predicted target genes of these miRNAs are involved in inflammation, pain, and related pathways. miR-10a-5p showed the highest expression levels in AP. Overexpression of miR-10a-5p in LPS-challenged stem cells from the apical papilla resulted in down-regulation of messenger RNA levels of TNFA and up-regulation of interleukin IL10. RNA sequencing of K-562 cells treated with miR-10a-5p mimics and inhibitors identified miR-10a-5p target genes associated with multiple pathways, including macrophage-mediated inflammation and coagulation pathways. CONCLUSIONS Over 100 miRNAs were differentially expressed in AP and appeared to be involved with modulation of genes in inflammatory and immune pathways. MiR-10a-5p was the most significantly up-regulated miRNA in AP and may play a critical role in suppressing inflammation and promoting healing.
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Affiliation(s)
- Zhen Shen
- Department of Endodontics, University of Texas Health Science Center at Houston, School of Dentistry at Houston, Houston, Texas
| | - Caroline Wichnieski
- Department of Endodontics, Pontifical Catholic University of Paraná, Curitiba, Paraná, Brazil
| | - Everdan Carneiro
- Department of Endodontics, Pontifical Catholic University of Paraná, Curitiba, Paraná, Brazil
| | - Gustavo P Garlet
- Department of Biological Sciences, School of Dentistry of Bauru, University of São Paulo, Bauru, São Paulo, Brazil
| | - Ariadne Letra
- Center for Craniofacial Research, University of Texas School of Dentistry at Houston, Houston, Texas; Department of Diagnostic and Biomedical Sciences, University of Texas Health Science Center at Houston, School of Dentistry at Houston, Houston, Texas
| | - Renato M Silva
- Department of Endodontics, University of Texas Health Science Center at Houston, School of Dentistry at Houston, Houston, Texas; Center for Craniofacial Research, University of Texas School of Dentistry at Houston, Houston, Texas.
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Wang D, Sun S, Xue Y, Qiu J, Ye T, Zhang R, Song B, He W, Zhang Y, Jiang W. MicroRNA-223 negatively regulates LPS-induced inflammatory responses by targeting NLRP3 in human dental pulp fibroblasts. Int Endod J 2020; 54:241-254. [PMID: 32966618 DOI: 10.1111/iej.13413] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 09/08/2020] [Accepted: 09/14/2020] [Indexed: 12/11/2022]
Abstract
AIM To investigate the effect of miR-223 on NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway-mediated proinflammatory cytokines IL-1β and IL-18 in human dental pulp fibroblasts (HDPFs). METHODOLOGY Human dental pulp tissue (HDPT) and HDPFs were obtained from impacted third molars. The miR-223 mimics and inhibitor or NLRP3 plasmid were used to upregulate or downregulate miR-223 or NLRP3 in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay was conducted to confirm target association. The mRNA and protein expression of NLRP3, caspase-1, IL-1β and IL-18 was determined by qRT-PCR and Western blotting, respectively. The release of IL-1β and IL-18 was analysed by ELISA. The significance of the differences between the experimental and the control groups was determined using one-way analysis of variance; P < 0.05 indicated statistical significance. RESULTS A decrease in miR-223 and an increase in NLRP3 in HDPT occurred during the transformation of reversible pulpitis into irreversible pulpitis compared to that in healthy pulp tissue (P < 0.05). The computational prediction and luciferase reporter assay confirmed that NLRP3 was a direct target of miR-223 in HDPFs. The miR-223 inhibitor further promoted ATP plus LPS-induced NLRP3/CASP1 inflammasome pathway activation compared to the ATP plus LPS-induced group (P < 0.05). In contrast, the miR-223 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS compared to the ATP plus LPS-induced group (P < 0.05). CONCLUSION MiR-223 served as a negative regulator involved in the control of the production and secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3. These data provide insight into the potential regulatory effects of miRNAs on the NLRP3 inflammasome, thus opening up novel potential therapeutic avenues for future endodontic treatment.
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Affiliation(s)
- D Wang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China.,Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - S Sun
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Y Xue
- Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - J Qiu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - T Ye
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - R Zhang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China.,Department of Stomatology, First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - B Song
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China.,School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
| | - W He
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - Y Zhang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China
| | - W Jiang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Operative Dentistry & Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an, China.,School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK
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Mei HX, Chen YL, Shi PL, Yang SR, Xu X, He JZ. [Advances in oral bacteria influencing host epigenetic regulation]. HUA XI KOU QIANG YI XUE ZA ZHI = HUAXI KOUQIANG YIXUE ZAZHI = WEST CHINA JOURNAL OF STOMATOLOGY 2020; 38:583-588. [PMID: 33085246 DOI: 10.7518/hxkq.2020.05.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Epigenetics refers to a steady change in the level of gene expression caused by non-DNA sequence changes. Microbes can modulate host inflammation through epigenetic pathways to evade or expend immune responses. As an important part of human microbes, oral bacteria also have various epigenetic regulation mechanisms to affect host inflammatory responses. This article reviews the common pathways of epigenetic regulation in microbe infection and the regulation of host epigenetics by using oral microbes to provide a reference for the study of epigenetic-related mechanisms in oral diseases.
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Affiliation(s)
- Hong-Xiang Mei
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Yi-Lin Chen
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Pei-Lei Shi
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Si-Rui Yang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Xin Xu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Jin-Zhi He
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
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Zhang K, Qiu W, Wu B, Fang F. Long non‑coding RNAs are novel players in oral inflammatory disorders, potentially premalignant oral epithelial lesions and oral squamous cell carcinoma (Review). Int J Mol Med 2020; 46:535-545. [PMID: 32626947 PMCID: PMC7307862 DOI: 10.3892/ijmm.2020.4628] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 05/15/2020] [Indexed: 12/14/2022] Open
Abstract
In recent years, a large number of studies have shown that the abnormal expression of long non‑coding (lnc)RNAs can lead to a variety of different diseases, including inflammatory disorders, cardiovascular disease, nervous system diseases, and cancers. Recent research has demonstrated the biological characteristics of lncRNAs and the important functions of lncRNAs in oral inflammation, precancerous lesions and cancers. The present review aims to explore and discuss the potential roles of candidate lncRNAs in oral diseases by summarizing multiple lncRNA profiles in diseased and healthy oral tissues to determine the altered lncRNA signatures. In addition, to highlight the exact regulatory mechanism of lncRNAs in oral inflammatory disorders, potentially premalignant oral epithelial lesions and oral squamous cell carcinoma. The detection of lncRNAs in oral samples has the potential to be used as a diagnostic and an early detection tool for oral diseases. Furthermore, lncRNAs are promising future therapeutic targets in oral diseases, and research in this field may expand in the future.
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Affiliation(s)
- Kaiying Zhang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P. R. China
| | - Wei Qiu
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P. R. China
| | - Buling Wu
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P. R. China
| | - Fuchun Fang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P. R. China
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Ebrahimi Ghahnavieh L, Tabatabaeian H, Ebrahimi Ghahnavieh Z, Honardoost MA, Azadeh M, Moazeni Bistgani M, Ghaedi K. Fluctuating expression of miR-584 in primary and high-grade gastric cancer. BMC Cancer 2020; 20:621. [PMID: 32615958 PMCID: PMC7345521 DOI: 10.1186/s12885-020-07116-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 06/25/2020] [Indexed: 12/24/2022] Open
Abstract
Background Gastric cancer is the fifth most common cancer worldwide. Along with environmental factors, such as Helicobacter pylori (H. pylori) infection, genetic changes play important roles in gastric tumor formations. miR-584 is a less well-characterized microRNA (miRNA), with apparent activity in human cancers. However, miR-584 expression pattern in gastric cancer development has remained unclear. This study aims to analyze the expression of miR-584 in gastric cancer samples and investigates the associations between this miRNA and H. pylori infection and clinical characteristics. Methods The expression level of miR-584 was studied in primary gastric cancers versus healthy control gastric mucosa samples using the RT-qPCR method. The clinical data were analyzed statistically in terms of miR-584 expression. In silico studies were employed to study miR-584 more broadly in order to assess its expression and find new potential target genes. Results Both experimental and in silico studies showed up-regulation of miR-584 in patients with gastric cancer. This up-regulation seems to be induced by H. pylori infection since the infected samples showed increased levels of miR-584 expression. Deeper analyses revealed that miR-584 undergoes a dramatic down-regulation in late stages, invasive and lymph node-metastatic gastric tumors. Bioinformatics studies demonstrated that miR-584 has a substantial role in cancer pathways and has the potential to target STAT1 transcripts. Consistent with the inverse correlation between TCGA RNA-seq data of miR-584 and STAT1 transcripts, the qPCR analysis showed a significant negative correlation between these two RNAs in a set of clinical samples. Conclusion miR-584 undergoes up-regulation in the stage of primary tumor formation; however, becomes down-regulated upon the progression of gastric cancer. These findings suggest the potential of miR-584 as a diagnostic or prognostic biomarker in gastric cancer.
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Affiliation(s)
| | - Hossein Tabatabaeian
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran. .,Anahid Cancer Clinic, Isfahan Healthcare City, Isfahan, Iran.
| | - Zhaleh Ebrahimi Ghahnavieh
- Department of Medical Education, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Mohammad Amin Honardoost
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | | | - Mohamad Moazeni Bistgani
- Department of Surgery, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Kamran Ghaedi
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran. .,Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
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Tian S, Liu Y, Dong F, Dou Y, Li W, Wang J. Knockdown of microRNA-584 promotes dental pulp stem cells proliferation by targeting TAZ. Cell Cycle 2020; 19:1048-1058. [PMID: 32208890 DOI: 10.1080/15384101.2020.1744976] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Proliferation of dental pulp stem cells (DPSCs) is crucial in tooth development and damage repairing, also includes its therapy application for tissue engineering. MicroRNAs (miRNAs) are key players in biological processes of DPSCs, and transcriptional co-activator with PDZ-binding motif (TAZ) also plays important roles in cell proliferation and differentiation, however, the roles of miR-584 and TAZ in DPSCs are not known. We found up-regulated miR-584 expression and down-regulated TAZ expression levels in aging dental pulp tissue compare to those in young dental pulp tissue. In proliferating DPSCs we demonstrated the decreased miR-584 expression and increased TAZ expression. miR-584 mimics suppressed DPSCs proliferation and migration, and significantly reduced TAZ production, whereas miR-584 inhibition exerted the converse effects. Knocking down of the TAZ in DPSCs had a similar effect as overexpression of miR-584. Furthermore, luciferase reporter assay demonstrated that miR-584 could directly bind to the TAZ mRNA 3'UTR to repress its translation. Overexpression of TAZ can partly rescue miR-584 mimic-mediated the inhibition of proliferation. Additionally, miR-584 inhibited cell proliferation and downregulated expression of cell cycle proteins by AKT signaling pathway. Together, we identified that miR-584 may be a key regulator in the proliferation of DPSCs by regulating TAZ expression via AKT signaling pathway. It would be a promising biomarker and therapeutic target for pulp disease.
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Affiliation(s)
- Songbo Tian
- Department of Oral Pathology, College of Stomatology, Hebei Medical University, Shijiazhuang, China.,Department of Oral Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yanping Liu
- Physical Examination Center, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Fusheng Dong
- Department of Oral and Maxillofacial Surgery, College of Stomatology, Hebei Medical University, Shijiazhuang, China
| | - Yongqing Dou
- College of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Wenjing Li
- Department of Oral Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jie Wang
- Department of Oral Pathology, College of Stomatology, Hebei Medical University, Shijiazhuang, China
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Gu J, Zhang J, Huang W, Tao T, Huang Y, Yang L, Yang J, Fan Y, Wang H. Activating miRNA-mRNA network in gemcitabine-resistant pancreatic cancer cell associates with alteration of memory CD4 + T cells. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:279. [PMID: 32355723 PMCID: PMC7186712 DOI: 10.21037/atm.2020.03.53] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background To identify key microRNAs (miRNAs) and their target mRNAs related to gemcitabine-resistant pancreatic cancer (PC) and investigate the association between gemcitabine-resistant-related miRNAs and mRNAs and immune infiltration. Methods Expression profiles of miRNAs and mRNAs were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed miRNAs and mRNAs (referred to as "DEmiRNAs" and "DEmRNAs", respectively) were distinguished between gemcitabine-resistant PC cells and its parental cells. The DEmRNAs targeted by the DEmiRNAs were retrieved using miRDB, microT, and Targetscan. Furthermore, GO and KEGG pathway enrichment analysis and GSEA were performed. The Kaplan-Meier plotter was used to analyze the prognosis of key DEmiRNAs and DEmRNAs on PC patients. The relationship between the key DEmRNAs and tumor-infiltrating immune cells in PC was investigated using CIBERSORT method using the LM22 signature as reference. Key infiltrating immune cells were further analyzed for the associations with prognosis of TCGA PAAD patients. Results Four DEmiRNAs, including hsa-miR-3178, hsa-miR-485-3p, hsa-miR-574-5p, and hsa-miR-584-5p, were identified to target seven DEmRNAs, including MSI2, TEAD1, GNPDA1, RND3, PRKACB, TRIM68, and YKT6, individually, in gemcitabine-resistant PC cells versus parental cells. Gemcitabine-resistant PC cells were enriched in proteasome-related, immune-related, and memory CD4+ T cell-related pathways, indicating a gemcitabine therapeutic effect on PC cells. All four DEmiRNAs and almost all DEmRNAs had an impact on the prognosis of PC patients. All seven DEmRNAs had remarkable effects on CD4+ memory T cells, which were affected by the gemcitabine therapeutic effect. Effector memory CD4+ T cells rather than central memory CD4+ T cells predicted a good prognosis according to the TCGA PAAD dataset. Conclusions Gemcitabine resistance can alter the fraction of memory CD4+ T cells via hsa-miR-3178, hsa-miR-485-3p, hsa-miR-574-5p and hsa-miR-584-5p targeted MSI2, TEAD1, GNPDA1, RND3, PRKACB, TRIM68, and YKT6 network in PC.
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Affiliation(s)
- Jianyou Gu
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Junfeng Zhang
- Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Wenjie Huang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.,Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510000, China
| | - Tian Tao
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Yaohuan Huang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Ludi Yang
- State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, China
| | - Jiali Yang
- Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Yingfang Fan
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
| | - Huaizhi Wang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 400038, China
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Fouad AF, Khan AA, Silva RM, Kang MK. Genetic and Epigenetic Characterization of Pulpal and Periapical Inflammation. Front Physiol 2020; 11:21. [PMID: 32116745 PMCID: PMC7010935 DOI: 10.3389/fphys.2020.00021] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Accepted: 01/13/2020] [Indexed: 12/18/2022] Open
Abstract
Pulpal and periapical diseases affect a large segment of the population. The role of microbial infections and host effector molecules in these diseases is well established. However, the interaction between host genes and environmental factors in disease susceptibility and progression is less well understood. Studies of genetic polymorphisms in disease relevant genes have suggested that individual predisposition may contribute to susceptibility to pulpal and periapical diseases. Other studies have explored the contribution of epigenetic mechanisms to these diseases. Ongoing research expands the spectrum of non-coding RNAs in pulpal disease to include viral microRNAs as well. This review summarizes recent advances in the genetic and epigenetic characterization of pulpal and periapical disease, with special emphasis on recent data that address the pathogenesis of irreversible pulpal pathosis and apical periodontitis. Specifically, proinflammatory and anti-inflammatory gene expression and gene polymorphism, as well as recent data on DNA methylation and microRNAs are reviewed. Improved understanding of these mechanisms may aid in disease prevention as well as in improved treatment outcomes.
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Affiliation(s)
- Ashraf F Fouad
- Division of Comprehensive Oral Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
| | - Asma A Khan
- Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
| | - Renato M Silva
- Department of Endodontics, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Mo K Kang
- Section of Endodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, United States
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Wang J, Du Y, Deng J, Wang X, Long F, He J. MicroRNA-506 Is Involved in Regulation of the Occurrence of Lipopolysaccharides (LPS)-Induced Pulpitis by Sirtuin 1 (SIRT1). Med Sci Monit 2019; 25:10008-10015. [PMID: 31877121 PMCID: PMC6944165 DOI: 10.12659/msm.918172] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Toothache often occurs with pulpitis. Lipopolysaccharide (LPS) is produced by gram-negative bacteria, and its accumulation is related to clinical symptoms of pain. MicroRNAs (miRNAs) display anti-inflammatory potential due to their direct regulation of cellular protein expression, which can promote inflammatory changes in dental pulp tissues. However, the mechanism of LPS-induced pulpitis is still unclear. Material/Methods In this study, dental pulp stem cells (DPSCs) were separated and cultured from rat dental pulp tissues; then, LPS was administered to induce inflammation and activate the TLR4 pathway. Results It was found that miR-506 was upregulated following LPS treatment in DPSCs. The inhibition of miR-506 in LPS-treated DPSCs led to attenuated inflammation and deactivation of the TLR4 pathway. Furthermore, the bioinformatic analysis and dual-luciferase reporter gene assay indicated that miR-506 could target the 3′-UTR of sirtuin 1 (SIRT1). Additionally, SIRT1 decreased in LPS-treated DPSCs, and miR-506 transfection resulted in SIRT1 upregulation. SIRT1 overexpression showed a similar inhibitory effect as that of miR-506 downregulation on inflammation and TLR4 activation in DPSCs. Conclusions In brief, miR-506 can protect dental pulp in LPS-induced inflammation by inhibiting the SIRT1-mediated TLR4 pathway.
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Affiliation(s)
- Jun Wang
- Stomatological Center, Gansu Provincial Hospital, Lanzhou, Gansu, China (mainland)
| | - Yi Du
- Department of Nursing, The First Hospital of Lanzhou University, Lanzhou, Gansu, China (mainland)
| | - Junhong Deng
- Department of Stomatology, The Second People's Hospital of Lanzhou City, Lanzhou, Gansu, China (mainland)
| | - Xin Wang
- Departments of Health and Social Care, The Second People's Hospital of Lanzhou City, Lanzhou, Gansu, China (mainland)
| | - Fei Long
- Stomatological Center, Gansu Provincial Hospital, Lanzhou, Gansu, China (mainland)
| | - Jianmin He
- Stomatological Center, Gansu Provincial Hospital, Lanzhou, Gansu, China (mainland)
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Fang F, Zhang K, Chen Z, Wu B. Noncoding RNAs: new insights into the odontogenic differentiation of dental tissue-derived mesenchymal stem cells. Stem Cell Res Ther 2019; 10:297. [PMID: 31547871 PMCID: PMC6757432 DOI: 10.1186/s13287-019-1411-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Revised: 08/28/2019] [Accepted: 09/05/2019] [Indexed: 12/11/2022] Open
Abstract
Odontoblasts are cells that contribute to the formation of the dental pulp complex. The differentiation of dental tissue-derived mesenchymal stem cells into odontoblasts comprises many factors and signaling pathways. Noncoding RNAs (ncRNAs), comprising a substantial part of poly-A tail mature RNAs, are considered “transcriptional noise.” Emerging evidence has shown that ncRNAs have key functions in the differentiation of mesenchymal stem cells. In this review, we discussed two major types of ncRNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), in terms of their role in the odontogenic differentiation of dental tissue-derived stem cells. Recent findings have demonstrated important functions for miRNAs and lncRNAs in odontogenic differentiation. It is expected that ncRNAs will become promising therapeutic targets for dentin regeneration based on stem cells.
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Affiliation(s)
- Fuchun Fang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong, People's Republic of China.,College of Stomatology, Southern Medical University, 1838 GuangZhou Avenue North, Guangzhou, 510515, Guangdong, People's Republic of China
| | - Kaiying Zhang
- Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong, People's Republic of China
| | - Zhao Chen
- Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong, People's Republic of China
| | - Buling Wu
- Department of Stomatology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong, People's Republic of China. .,College of Stomatology, Southern Medical University, 1838 GuangZhou Avenue North, Guangzhou, 510515, Guangdong, People's Republic of China.
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Brodzikowska A, Gondek A, Rak B, Paskal W, Pełka K, Cudnoch-Jędrzejewska A, Włodarski P. Metalloproteinase 14 (MMP-14) and hsa-miR-410-3p expression in human inflamed dental pulp and odontoblasts. Histochem Cell Biol 2019; 152:345-353. [PMID: 31486923 PMCID: PMC6842353 DOI: 10.1007/s00418-019-01811-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2019] [Indexed: 11/30/2022]
Abstract
The objective of this study is to evaluate MMP-14 expression in odontoblasts and in the bulk of dental pulp of teeth with pulpitis; to determine the expression of microRNA-410 (miR-410) in pulp tissue, since sequence analysis suggests that miR-410 has potential binding site on MMP-14’s 3′UTR, and hence, can regulate expression of the latter one. Tissue samples of dental pulp from teeth with pulpitis and healthy (control) were formalin fixed and paraffin embedded (FFPE). Samples were examined using immunohistochemical staining for MMP-14 and the expression of miR-410 was evaluated using qRT-PCR. In both, healthy and inflamed pulp odontoblasts stained more intensively than remaining pulp tissue, but this difference was not statistically significant. More positive staining was observed in inflamed pulps compared to healthy pulps. Expression of miR-410 was found significantly lower in inflamed pulps than in healthy ones. In the two examined zones, odontoblasts and remaining pulp, miR-410 was expressed on a similar level. No statistically significant correlation of miR-410 and MMP-14 expression was found. We showed that inflammation changes the MMP-14 expression in pulp tissue and odontoblasts. This study demonstrates for the first time miR-410 expression in human dental pulp and that expression of this microRNA was downregulated in inflamed dental pulp and odontoblasts.
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Affiliation(s)
- Aniela Brodzikowska
- The Department of Conservative Dentistry, Medical University of Warsaw, Miodowa 18, 00-246, Warsaw, Poland.
| | - Agata Gondek
- Laboratory of Centre for Preclinical Research, Department of Methodology, Medical University of Warsaw, Banacha 1b, 02-097, Warsaw, Poland
| | - Beata Rak
- Laboratory of Centre for Preclinical Research, Department of Methodology, Medical University of Warsaw, Banacha 1b, 02-097, Warsaw, Poland.,Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.,Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Banacha 1a, Warsaw, Poland
| | - Wiktor Paskal
- Laboratory of Centre for Preclinical Research, Department of Methodology, Medical University of Warsaw, Banacha 1b, 02-097, Warsaw, Poland
| | - Kacper Pełka
- Laboratory of Centre for Preclinical Research, Department of Methodology, Medical University of Warsaw, Banacha 1b, 02-097, Warsaw, Poland
| | - Agnieszka Cudnoch-Jędrzejewska
- Laboratory of Centre for Preclinical Research, Department of Experimental and Clinical Physiology, Medical University of Warsaw, Banacha 1b, 02-097, Warsaw, Poland
| | - Paweł Włodarski
- Laboratory of Centre for Preclinical Research, Department of Methodology, Medical University of Warsaw, Banacha 1b, 02-097, Warsaw, Poland
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Yue W, Kim S, Jung HS, Lee JM, Lee S, Kim E. Differential Protein Expression in Human Dental Pulp: Comparison of Healthy, Inflamed, and Traumatic Pulp. J Clin Med 2019; 8:jcm8081234. [PMID: 31426363 PMCID: PMC6723928 DOI: 10.3390/jcm8081234] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Accepted: 08/14/2019] [Indexed: 12/19/2022] Open
Abstract
Trauma or injury to the dental pulp causes inflammation. This study compared the proteome of healthy pulp with inflamed pulp and traumatic pulp to identify the differentially expressed proteins in the diseased state. Five participants were grouped based on the pulpal status of the teeth: healthy, inflamed, or traumatic pulp. Pulp was extirpated and stored immediately in liquid nitrogen. Pulp tissues were subjected to 2-dimensional gel electrophoresis, and spot selection was performed. The selected spots were analyzed using liquid chromatography-tandem mass spectrometry and identified by correlating mass spectra to the proteomic databases. Fifteen spots showed increased expression in the inflamed and traumatic pulp. Annexin V, type II keratin, and hemoglobin levels were increased two-fold in the inflamed and traumatic pulp group and annexin V, mutant beta-actin, and hemoglobin were increased by ten-fold in the inflamed or traumatic pulp group, compared to levels in the healthy pulp group. Annexin V constituted two out of fifteen protein spots, and seemed to play a critical role in inhibiting inflammation and promoting the immune reaction. Further studies on this protein concerning its role in pulp repair are necessary to elucidate the underlying mechanisms.
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Affiliation(s)
- Wonyoung Yue
- Microscope Center, Department of Conservative Dentistry and Oral Science Research Center, College of Dentistry, Yonsei University, Seoul 03722, Korea
| | - Sunil Kim
- Microscope Center, Department of Conservative Dentistry and Oral Science Research Center, College of Dentistry, Yonsei University, Seoul 03722, Korea
| | - Han-Sung Jung
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul 03722, Korea
| | - Jong-Min Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Oral Science Research Center, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul 03722, Korea
| | - Sukjoon Lee
- Department of Applied Life Science, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul 03722, Korea
| | - Euiseong Kim
- Microscope Center, Department of Conservative Dentistry and Oral Science Research Center, College of Dentistry, Yonsei University, Seoul 03722, Korea.
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Mo Z, Li Q, Cai L, Zhan M, Xu Q. The effect of DNA methylation on the miRNA expression pattern in lipopolysaccharide-induced inflammatory responses in human dental pulp cells. Mol Immunol 2019; 111:11-18. [PMID: 30952010 DOI: 10.1016/j.molimm.2019.03.012] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 02/07/2019] [Accepted: 03/26/2019] [Indexed: 02/06/2023]
Abstract
Endodontic infection is a widespread oral problem. DNA methylation is a key epigenetic modification that plays important roles in various inflammatory responses, but its role in dental pulp inflammation is poorly understood. In this study, we assessed the expression of DNA methyltransferases (DNMTs) in human dental pulp cells (hDPCs) during lipopolysaccharide (LPS)-induced inflammation and found that DNMT3B mRNA expression was reduced and DNMT1 mRNA and protein levels decreased significantly. Pretreatment with the DNMT inhibitor 5-Aza-2'-deoxycytidine (5-Aza-CdR) significantly enhanced the expression of the inflammatory cytokines IL-6 and IL-8 in LPS-stimulated hDPCs, indicating that DNA methylation may play a role in hDPC inflammation. Studies have reported that some microRNAs (miRNAs) are involved in dental pulp infection. DNA methylation can modulate the inflammatory response by regulating miRNA expression, but this phenomenon has not yet been reported in pulp inflammation. The present study used next-generation sequencing to examine the effect of 5-Aza-CdR on the miRNA expression profile of LPS-treated hDPCs, and the results showed that 5-Aza-CdR pretreatment changed the miRNA expression pattern in hDPCs during inflammation. Among the changed miRNAs, miR-146a-5p, which is a pulp inflammation-related miRNA, demonstrated the most noticeably altered expression. miR-146a-5p could be induced by LPS in hDPCs, and 5-Aza-CdR preincubation or DNMT1 knockdown markedly increased its expression level. However, no significant difference was found in the methylation pattern of the MIR146A promoter with 5-Aza-CdR pretreatment or DNMT1 knockdown in LPS-stimulated hDPCs. These results indicate that DNA methylation may regulate the LPS-induced inflammatory response by changing the miRNA expression in hDPCs.
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Affiliation(s)
- Zehuan Mo
- Guanghua School of Stomatology & Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, Guangdong, People's Republic of China.
| | - Qimeng Li
- Guanghua School of Stomatology & Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, Guangdong, People's Republic of China.
| | - Luhui Cai
- Guanghua School of Stomatology & Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, Guangdong, People's Republic of China.
| | - Minkang Zhan
- Guanghua School of Stomatology & Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, Guangdong, People's Republic of China.
| | - Qiong Xu
- Guanghua School of Stomatology & Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, Guangdong, People's Republic of China.
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Lei F, Zhang H, Xie X. Comprehensive analysis of an lncRNA-miRNA-mRNA competing endogenous RNA network in pulpitis. PeerJ 2019; 7:e7135. [PMID: 31304055 PMCID: PMC6609876 DOI: 10.7717/peerj.7135] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Accepted: 05/16/2019] [Indexed: 12/30/2022] Open
Abstract
Background Pulpitis is a common inflammatory disease that affects dental pulp. It is important to understand the molecular signals of inflammation and repair associated with this process. Increasing evidence has revealed that long noncoding RNAs (lncRNAs), via competitively sponging microRNAs (miRNAs), can act as competing endogenous RNAs (ceRNAs) to regulate inflammation and reparative responses. The aim of this study was to elucidate the potential roles of lncRNA, miRNA and messenger RNA (mRNA) ceRNA networks in pulpitis tissues compared to normal control tissues. Methods The oligo and limma packages were used to identify differentially expressed lncRNAs and mRNAs (DElncRNAs and DEmRNAs, respectively) based on expression profiles in two datasets, GSE92681 and GSE77459, from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were further analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein–protein interaction (PPI) networks and modules were established to screen hub genes using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and the Molecular Complex Detection (MCODE) plugin for Cytoscape, respectively. Furthermore, an lncRNA-miRNA-mRNA-hub genes regulatory network was constructed to investigate mechanisms related to the progression and prognosis of pulpitis. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to verify critical lncRNAs that may significantly affect the pathogenesis in inflamed and normal human dental pulp. Results A total of 644 upregulated and 264 downregulated differentially expressed genes (DEGs) in pulpitis samples were identified from the GSE77459 dataset, while 8 up- and 19 downregulated probes associated with lncRNA were identified from the GSE92681 dataset. Protein–protein interaction (PPI) based on STRING analysis revealed a network of DEGs containing 4,929 edges and 623 nodes. Upon combined analysis of the constructed PPI network and the MCODE results, 10 hub genes, including IL6, IL8, PTPRC, IL1B, TLR2, ITGAM, CCL2, PIK3CG, ICAM1, and PIK3CD, were detected in the network. Next, a ceRNA regulatory relationship consisting of one lncRNA (PVT1), one miRNA (hsa-miR-455-5p) and two mRNAs (SOCS3 and PLXNC1) was established. Then, we constructed the network in which the regulatory relationship between ceRNA and hub genes was summarized. Finally, our qRT-PCR results confirmed significantly higher levels of PVT1 transcript in inflamed pulp than in normal pulp tissues (p = 0.03). Conclusion Our study identified a novel lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of pulpitis.
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Affiliation(s)
- Fangcao Lei
- Department of Operative Dentistry and Endodontics, School of Stomatology, Xiangya Stomatological Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Han Zhang
- Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan, People's Republic of China
| | - Xiaoli Xie
- Department of Operative Dentistry and Endodontics, School of Stomatology, Xiangya Stomatological Hospital, Central South University, Changsha, Hunan, People's Republic of China
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