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Global MicroRNA Profiling in Human Bone Marrow Skeletal—Stromal or Mesenchymal–Stem Cells Identified Candidates for Bone Regeneration

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  • Chi Chih Chang
  • ,
  • Morten T. Venø
  • ,
  • Li Chen, Syddansk universitet
  • ,
  • Nicholas Ditzel, Syddansk universitet
  • ,
  • Dang Q.S. Le
  • Philipp Dillschneider, Department of Prosthetic Dentistry and Biomedical Materials Science, Hannover Medical School
  • ,
  • Moustapha Kassem, Syddansk universitet, The Danish Stem Cell Center (DanStem), Københavns Universitet, Stem Cell Unit, King Saud University, Riyadh
  • ,
  • Jørgen Kjems

Bone remodeling and regeneration are highly regulated multistep processes involving posttranscriptional regulation by microRNAs (miRNAs). Here, we performed a global profiling of differentially expressed miRNAs in bone-marrow-derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem cells) during in vitro osteoblast differentiation. We functionally validated the regulatory effects of several miRNAs on osteoblast differentiation and identified 15 miRNAs, most significantly miR-222 and miR-423, as regulators of osteoblastogenesis. In addition, we tested the possible targeting of miRNAs for enhancing bone tissue regeneration. Scaffolds functionalized with miRNA nano-carriers enhanced osteoblastogenesis in 3D culture and retained this ability at least 2 weeks after storage. Additionally, anti-miR-222 enhanced in vivo ectopic bone formation through targeting the cell-cycle inhibitor CDKN1B (cyclin-dependent kinase inhibitor 1B). A number of additional miRNAs exerted additive osteoinductive effects on BMSC differentiation, suggesting that pools of miRNAs delivered locally from an implanted scaffold can provide a promising approach for enhanced bone regeneration. Bone regeneration is a multistep process involving posttranscriptional regulation by miRNAs. We profiled differentially expressed miRNAs in BMSCs during osteoblast differentiation, and we functionally validated 15 miRNAs, most significantly miR-222 and miR-423, as regulators of osteoblastogenesis. miRNA-functionalized scaffolds enhanced osteoblastogenesis, suggesting local delivery is a promising approach for bone regeneration.

Original languageEnglish
JournalMolecular Therapy
Volume26
Issue2
Pages (from-to)593-605
Number of pages13
ISSN1525-0016
DOIs
Publication statusPublished - 7 Feb 2018

    Research areas

  • bone regeneration, cell cycle regulation, mesenchymal stem cells, miRNA profiling, miRNAs, osteogenesis, RNAi therapeutics, scaffold, small RNA-seq, tissue engineering

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