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

TY - JOUR

T1 - Global MicroRNA Profiling in Human Bone Marrow Skeletal-Stromal or Mesenchymal-Stem Cells Identified Candidates for Bone Regeneration

AU - Chang, Chi-Chih

AU - Venø, Morten T

AU - Chen, Li

AU - Ditzel, Nicholas

AU - Le, Dang Q S

AU - Dillschneider, Philipp

AU - Kassem, Moustapha

AU - Kjems, Jørgen

N1 - Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

PY - 2018/2/7

Y1 - 2018/2/7

N2 - 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.

AB - 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.

U2 - 10.1016/j.ymthe.2017.11.018

DO - 10.1016/j.ymthe.2017.11.018

M3 - Journal article

C2 - 29331291

SN - 1525-0016

VL - 26

SP - 593

EP - 605

JO - Molecular Therapy

JF - Molecular Therapy

IS - 2

ER -