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, JF3
Fu, WM4
He, ML4
Xie, WD3
Lv, Q3
Wan, G3
Li, G4
Wang, H4
Lu, G4
Hu, X1
Jiang, S1
Li, JN3
Lin, MCM4
Zhang, YO3
Kung, HF2 4
KeywordsBmp Signaling Pathway
Co-Regulatory Pattern
Mesenchymal Stem Cell
Mir-20A
Osteogenic Differentiation
Issue Date2011
CitationRna Biology, 2011, v. 8 n. 5 [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
2011 Impact Factor: 4.933
2011 SCImago Journal Rankings: 0.570
ReferencesReferences in Scopus
DC Field
Value
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_subscribed_fulltext
dc.identifier.citationRna Biology, 2011, v. 8 n. 5 [How to Cite?]
dc.identifier.issn1547-6286
2011 Impact Factor: 4.933
2011 SCImago Journal Rankings: 0.570
dc.identifier.issue5
dc.identifier.scopuseid_2-s2.0-80052786029
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
Author Affiliations
  1. R and D Center of Stem Cell
  2. Sun Yat-Sen University
  3. Tsinghua University
  4. Chinese University of Hong Kong