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Article: MiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling
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TitleMiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling
 
AuthorsZhang, JF4
Fu, WM5
He, ML5
Xie, WD4
Lv, Q4
Wan, G4
Li, G5
Wang, H5
Lu, G2
Hu, X1
Jiang, S1
Li, JN4
Lin, MCM2
Zhang, YO4
Kung, HF5 3
 
KeywordsBmp Signaling Pathway
Co-Regulatory Pattern
Mesenchymal Stem Cell
Mir-20A
Osteogenic Differentiation
 
Issue Date2011
 
CitationRNA Biology, 2011, v. 8 n. 5, p. 829-838 [How to Cite?]
 
AbstractOsteogenic differentiation of mesenchymal stem cells (MSCs) is a complex process, which is regulated by various factors including microRNAs. Our preliminary data showed that the expression of endogenous miR-20a was increased during the course of osteogenic differentiation. Simultaneously, the expression of osteoblast markers and regulators BMP2, BMP4, Runx2, Osx, OCN and OPN was also elevated whereas adipocyte markers PPARγ and osteoblast antagonist, Bambi and Crim1, were downregulated, thereby suggesting that miR-20a plays an important role in regulating osteoblast differentiation. To validate this hypothesis, we tested its effects on osteogenic differentiation by introducing miR- 20a mimics and lentiviral-miR20a-expression vectors into hMSCs. We showed that miR-20a promoted osteogenic differentiation by the upregulation of BMP/Runx2 signaling. We performed bioinformatics analysis and predicted that PPARγ, Bambi and Crim1 would be potential targets of miR-20a. PPARγ is a negative regulator of BMP/Runx2 signaling whereas Bambi or Crim1 are antagonists of the BMP pathway. Furthermore, we confirmed that all these molecules were indeed the targets of miR-20a by luciferase reporter, quantitative RT-PCR and western blot assays. Similarly to miR-20a overexpression, the osteogenesis was enhanced by the silence of PPARγ, Bambi or Crim1 by specific siRNAs. Taken together, for the first time, we demonstrated that miR-20a promoted the osteogenesis of hMSCs in a co-regulatory pattern by targeting PPARγ, Bambi and Crim1, the negative regulators of BMP signaling. © 2011 Landes Bioscience.
 
ISSN1547-6286
2012 Impact Factor: 4.841
2012 SCImago Journal Rankings: 1.664
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorZhang, JF
 
dc.contributor.authorFu, WM
 
dc.contributor.authorHe, ML
 
dc.contributor.authorXie, WD
 
dc.contributor.authorLv, Q
 
dc.contributor.authorWan, G
 
dc.contributor.authorLi, G
 
dc.contributor.authorWang, H
 
dc.contributor.authorLu, G
 
dc.contributor.authorHu, X
 
dc.contributor.authorJiang, S
 
dc.contributor.authorLi, JN
 
dc.contributor.authorLin, MCM
 
dc.contributor.authorZhang, YO
 
dc.contributor.authorKung, HF
 
dc.date.accessioned2012-10-08T03:20:46Z
 
dc.date.available2012-10-08T03:20:46Z
 
dc.date.issued2011
 
dc.description.abstractOsteogenic differentiation of mesenchymal stem cells (MSCs) is a complex process, which is regulated by various factors including microRNAs. Our preliminary data showed that the expression of endogenous miR-20a was increased during the course of osteogenic differentiation. Simultaneously, the expression of osteoblast markers and regulators BMP2, BMP4, Runx2, Osx, OCN and OPN was also elevated whereas adipocyte markers PPARγ and osteoblast antagonist, Bambi and Crim1, were downregulated, thereby suggesting that miR-20a plays an important role in regulating osteoblast differentiation. To validate this hypothesis, we tested its effects on osteogenic differentiation by introducing miR- 20a mimics and lentiviral-miR20a-expression vectors into hMSCs. We showed that miR-20a promoted osteogenic differentiation by the upregulation of BMP/Runx2 signaling. We performed bioinformatics analysis and predicted that PPARγ, Bambi and Crim1 would be potential targets of miR-20a. PPARγ is a negative regulator of BMP/Runx2 signaling whereas Bambi or Crim1 are antagonists of the BMP pathway. Furthermore, we confirmed that all these molecules were indeed the targets of miR-20a by luciferase reporter, quantitative RT-PCR and western blot assays. Similarly to miR-20a overexpression, the osteogenesis was enhanced by the silence of PPARγ, Bambi or Crim1 by specific siRNAs. Taken together, for the first time, we demonstrated that miR-20a promoted the osteogenesis of hMSCs in a co-regulatory pattern by targeting PPARγ, Bambi and Crim1, the negative regulators of BMP signaling. © 2011 Landes Bioscience.
 
dc.description.natureLink_to_OA_fulltext
 
dc.identifier.citationRNA Biology, 2011, v. 8 n. 5, p. 829-838 [How to Cite?]
 
dc.identifier.epage838
 
dc.identifier.issn1547-6286
2012 Impact Factor: 4.841
2012 SCImago Journal Rankings: 1.664
 
dc.identifier.issue5
 
dc.identifier.pmid21743293
 
dc.identifier.scopuseid_2-s2.0-80052786029
 
dc.identifier.spage829
 
dc.identifier.urihttp://hdl.handle.net/10722/168563
 
dc.identifier.volume8
 
dc.languageeng
 
dc.relation.ispartofRNA Biology
 
dc.relation.referencesReferences in Scopus
 
dc.subjectBmp Signaling Pathway
 
dc.subjectCo-Regulatory Pattern
 
dc.subjectMesenchymal Stem Cell
 
dc.subjectMir-20A
 
dc.subjectOsteogenic Differentiation
 
dc.titleMiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling
 
dc.typeArticle
 
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<contributor.author>Wang, H</contributor.author>
<contributor.author>Lu, G</contributor.author>
<contributor.author>Hu, X</contributor.author>
<contributor.author>Jiang, S</contributor.author>
<contributor.author>Li, JN</contributor.author>
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<description.abstract>Osteogenic differentiation of mesenchymal stem cells (MSCs) is a complex process, which is regulated by various factors including microRNAs. Our preliminary data showed that the expression of endogenous miR-20a was increased during the course of osteogenic differentiation. Simultaneously, the expression of osteoblast markers and regulators BMP2, BMP4, Runx2, Osx, OCN and OPN was also elevated whereas adipocyte markers PPAR&#947; and osteoblast antagonist, Bambi and Crim1, were downregulated, thereby suggesting that miR-20a plays an important role in regulating osteoblast differentiation. To validate this hypothesis, we tested its effects on osteogenic differentiation by introducing miR- 20a mimics and lentiviral-miR20a-expression vectors into hMSCs. We showed that miR-20a promoted osteogenic differentiation by the upregulation of BMP/Runx2 signaling. We performed bioinformatics analysis and predicted that PPAR&#947;, Bambi and Crim1 would be potential targets of miR-20a. PPAR&#947; is a negative regulator of BMP/Runx2 signaling whereas Bambi or Crim1 are antagonists of the BMP pathway. Furthermore, we confirmed that all these molecules were indeed the targets of miR-20a by luciferase reporter, quantitative RT-PCR and western blot assays. Similarly to miR-20a overexpression, the osteogenesis was enhanced by the silence of PPAR&#947;, Bambi or Crim1 by specific siRNAs. Taken together, for the first time, we demonstrated that miR-20a promoted the osteogenesis of hMSCs in a co-regulatory pattern by targeting PPAR&#947;, Bambi and Crim1, the negative regulators of BMP signaling. &#169; 2011 Landes Bioscience.</description.abstract>
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Author Affiliations
  1. R and D Center of Stem Cell
  2. Prince of Wales Hospital Hong Kong
  3. Sun Yat-Sen University
  4. Tsinghua University
  5. Chinese University of Hong Kong