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

Chi-Chih Chang, Morten T Venø, Li Chen, Nicholas Ditzel, Dang Q S Le, Philipp Dillschneider, Moustapha Kassem, Jørgen Kjems

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Resumé

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.

OriginalsprogEngelsk
TidsskriftMolecular Therapy
Vol/bind26
Udgave nummer2
Sider (fra-til)593-605
ISSN1525-0016
DOI
StatusUdgivet - 7. feb. 2018

Fingeraftryk

MicroRNAs
Mesenchymal Stromal Cells
Osteoblasts
Osteogenesis
Cell Cycle

Citer dette

Chang, Chi-Chih ; Venø, Morten T ; Chen, Li ; Ditzel, Nicholas ; Le, Dang Q S ; Dillschneider, Philipp ; Kassem, Moustapha ; Kjems, Jørgen. / Global MicroRNA Profiling in Human Bone Marrow Skeletal-Stromal or Mesenchymal-Stem Cells Identified Candidates for Bone Regeneration. I: Molecular Therapy. 2018 ; Bind 26, Nr. 2. s. 593-605.
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title = "Global MicroRNA Profiling in Human Bone Marrow Skeletal-Stromal or Mesenchymal-Stem Cells Identified Candidates for Bone Regeneration",
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. 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.",
keywords = "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",
author = "Chi-Chih Chang and Ven{\o}, {Morten T} and Li Chen and Nicholas Ditzel and Le, {Dang Q S} and Philipp Dillschneider and Moustapha Kassem and J{\o}rgen Kjems",
note = "Copyright {\circledC} 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = "2",
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pages = "593--605",
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Global MicroRNA Profiling in Human Bone Marrow Skeletal-Stromal or Mesenchymal-Stem Cells Identified Candidates for Bone Regeneration. / Chang, Chi-Chih; Venø, Morten T; Chen, Li; Ditzel, Nicholas; Le, Dang Q S; Dillschneider, Philipp; Kassem, Moustapha; Kjems, Jørgen.

I: Molecular Therapy, Bind 26, Nr. 2, 07.02.2018, s. 593-605.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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.

KW - 3' Untranslated Regions

KW - Antagomirs/genetics

KW - Biomarkers

KW - Bone Regeneration/genetics

KW - Cell Cycle/genetics

KW - Cell Differentiation/genetics

KW - Cell Line

KW - Computational Biology/methods

KW - Ectopic Gene Expression

KW - Gene Expression Profiling

KW - Gene Expression Regulation

KW - Gene Transfer Techniques

KW - Humans

KW - Mesenchymal Stem Cells/metabolism

KW - MicroRNAs/genetics

KW - Osteogenesis/genetics

KW - Transcriptome

U2 - 10.1016/j.ymthe.2017.11.018

DO - 10.1016/j.ymthe.2017.11.018

M3 - Journal article

C2 - 29331291

VL - 26

SP - 593

EP - 605

JO - Molecular Therapy

JF - Molecular Therapy

SN - 1525-0016

IS - 2

ER -