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

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

Author information

1
Department of Molecular Biology and Genetics, Aarhus University, Aarhus 8000, Denmark.
2
Department of Molecular Biology and Genetics, Aarhus University, Aarhus 8000, Denmark; Interdisciplinary Nanoscience Center, Aarhus University, Aarhus 8000, Denmark.
3
Department of Endocrinology and Metabolism, Endocrine Research Laboratory (KMEB), Odense University Hospital & University of Southern Denmark, Odense 5000, Denmark.
4
Department of Clinical Medicine, Aarhus University, Aarhus 8000, Denmark.
5
Department of Molecular Biology and Genetics, Aarhus University, Aarhus 8000, Denmark; Interdisciplinary Nanoscience Center, Aarhus University, Aarhus 8000, Denmark; Department of Prosthetic Dentistry and Biomedical Materials Science, Hannover Medical School, Hannover 30625, Germany.
6
Department of Endocrinology and Metabolism, Endocrine Research Laboratory (KMEB), Odense University Hospital & University of Southern Denmark, Odense 5000, Denmark; The Danish Stem Cell Center (DanStem), University of Copenhagen, Copenhagen 2200, Denmark; Stem Cell Unit, Department of Anatomy, Faculty of Medicine, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
7
Department of Molecular Biology and Genetics, Aarhus University, Aarhus 8000, Denmark; Interdisciplinary Nanoscience Center, Aarhus University, Aarhus 8000, Denmark. Electronic address: kjems@inano.au.dk.

Abstract

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

PMID:
29331291
PMCID:
PMC5835027
DOI:
10.1016/j.ymthe.2017.11.018
[Indexed for MEDLINE]
Free PMC Article

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