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

Mol Ther. 2018 Feb 7;26(2):593-605. doi: 10.1016/j.ymthe.2017.11.018. Epub 2017 Dec 5.


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.

Keywords: RNAi therapeutics; bone regeneration; cell cycle regulation; mesenchymal stem cells; miRNA profiling; miRNAs; osteogenesis; scaffold; small RNA-seq; tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Antagomirs / genetics
  • Biomarkers
  • Bone Regeneration / genetics*
  • Cell Cycle / genetics
  • Cell Differentiation / genetics
  • Cell Line
  • Computational Biology / methods
  • Ectopic Gene Expression
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Gene Transfer Techniques
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics*
  • Osteogenesis / genetics
  • Transcriptome*


  • 3' Untranslated Regions
  • Antagomirs
  • Biomarkers
  • MicroRNAs