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Micrornas-Mediated Regulation of the Differentiation of Dental Pulp-Derived Mesenchymal Stem Cells: A Systematic Review and Bioinformatic Analysis Publisher Pubmed



Iranmanesh P1 ; Vedaei A2 ; Salehimazandarani S3 ; Nikpour P3 ; Khazaei S4 ; Khademi A1 ; Galler KM5 ; Nekoofar MH6, 8, 9 ; Dummer PMH7
Authors
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Authors Affiliations
  1. 1. Dental Research Center, Department of Endodontics, Dental Research Institute, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Student Research Committee, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Department of Endodontics, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
  5. 5. Department of Conservative Dentistry and Periodontology, University Hospital Erlangen, Erlangen, Germany
  6. 6. Department of Endodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom
  8. 8. Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Department of Endodontics, Bahcesehir University School of Dentistry, Istanbul, Turkey

Source: Stem Cell Research and Therapy Published:2023


Abstract

Background: Human dental pulp-derived mesenchymal stem cells (hDP-MSCs), which include human dental pulp stem cells (hDPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs), are promising cell sources for regenerative therapies. Nevertheless, a lack of knowledge relating to the mechanisms regulating their differentiation has limited their clinical application. microRNAs (miRNAs) are important regulatory molecules in cellular processes including cell differentiation. This systematic review aims to provide a panel of miRNAs that regulate the differentiation of hDP-MSCs including hDPSCs and SHEDs. Additionally, bioinformatic analyses were conducted to discover target genes, signaling pathways and gene ontologies associated with the identified miRNAs. Methods: A literature search was performed in MEDLINE (via PubMed), Web of Science, Scopus, Embase and Cochrane Library. Experimental studies assessing the promotive/suppressive effect of miRNAs on the differentiation of hDP-MSCs and studies evaluating changes to the expression of miRNAs during the differentiation of hDP-MSCs were included. miRNAs involved in odontogenic/osteogenic differentiation were then included in a bioinformatic analysis. A miRNA-mRNA network was constructed, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. A protein–protein interaction (PPI) network was also constructed. Results: Of 766 initially identified records through database searching, 42 and 36 studies were included in qualitative synthesis and bioinformatic analyses, respectively. Thirteen miRNAs promoted and 17 suppressed odontogenic/osteogenic differentiation of hDP-MSCs. hsa-miR-140-5p, hsa-miR-218 and hsa-miR-143 were more frequently reported suppressing the odontogenic/osteogenic differentiation of hDP-MSCs. hsa-miR-221 and hsa-miR-124 promoted and hsa-miR-140-5p inhibited neuronal differentiation, hsa-miR-26a-5p promoted and hsa-miR-424 suppressed angiogenic differentiation, and hsa-miR-135 and hsa-miR-143 inhibited differentiation within myogenic lineages. A miRNA-mRNA network including 1890 nodes and 2171 edges was constructed. KEGG pathway analysis revealed MAPK, PI3K-Akt and FoxO as key signaling pathways involved in the odontogenic/osteogenic differentiation of hDP-MSCs. Conclusions: The findings of this systematic review support the potential application of the specific miRNAs to regulate the directed differentiation of hDP-MSCs in the field of regenerative therapies. © 2023, The Author(s).
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