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Article: MiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling

TitleMiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling
Authors
KeywordsBmp Signaling Pathway
Co-Regulatory Pattern
Mesenchymal Stem Cell
Mir-20A
Osteogenic Differentiation
Issue Date2011
Citation
RNA 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.
Persistent Identifierhttp://hdl.handle.net/10722/168563
ISSN
2014 Impact Factor: 4.974
2014 SCImago Journal Rankings: 2.336
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhang, JFen_US
dc.contributor.authorFu, WMen_US
dc.contributor.authorHe, MLen_US
dc.contributor.authorXie, WDen_US
dc.contributor.authorLv, Qen_US
dc.contributor.authorWan, Gen_US
dc.contributor.authorLi, Gen_US
dc.contributor.authorWang, Hen_US
dc.contributor.authorLu, Gen_US
dc.contributor.authorHu, Xen_US
dc.contributor.authorJiang, Sen_US
dc.contributor.authorLi, JNen_US
dc.contributor.authorLin, MCMen_US
dc.contributor.authorZhang, YOen_US
dc.contributor.authorKung, HFen_US
dc.date.accessioned2012-10-08T03:20:46Z-
dc.date.available2012-10-08T03:20:46Z-
dc.date.issued2011en_US
dc.identifier.citationRNA Biology, 2011, v. 8 n. 5, p. 829-838en_US
dc.identifier.issn1547-6286en_US
dc.identifier.urihttp://hdl.handle.net/10722/168563-
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.en_US
dc.languageengen_US
dc.relation.ispartofRNA Biologyen_US
dc.subjectBmp Signaling Pathwayen_US
dc.subjectCo-Regulatory Patternen_US
dc.subjectMesenchymal Stem Cellen_US
dc.subjectMir-20Aen_US
dc.subjectOsteogenic Differentiationen_US
dc.titleMiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signalingen_US
dc.typeArticleen_US
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_US
dc.identifier.authorityLin, MCM=rp00746en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.4161/rna.8.5.16043-
dc.identifier.pmid21743293-
dc.identifier.scopuseid_2-s2.0-80052786029en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80052786029&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume8en_US
dc.identifier.issue5en_US
dc.identifier.spage829-
dc.identifier.epage838-
dc.identifier.isiWOS:000296567200017-
dc.identifier.scopusauthoridZhang, JF=13007942600en_US
dc.identifier.scopusauthoridFu, WM=52463551200en_US
dc.identifier.scopusauthoridHe, ML=35080389700en_US
dc.identifier.scopusauthoridXie, WD=35081557300en_US
dc.identifier.scopusauthoridLv, Q=27168890700en_US
dc.identifier.scopusauthoridWan, G=36912152700en_US
dc.identifier.scopusauthoridLi, G=7407055832en_US
dc.identifier.scopusauthoridWang, H=7501747965en_US
dc.identifier.scopusauthoridLu, G=36619108300en_US
dc.identifier.scopusauthoridHu, X=52463710500en_US
dc.identifier.scopusauthoridJiang, S=52463824700en_US
dc.identifier.scopusauthoridLi, JN=36910827400en_US
dc.identifier.scopusauthoridLin, MCM=7404816359en_US
dc.identifier.scopusauthoridZhang, YO=35338497900en_US
dc.identifier.scopusauthoridKung, HF=7402514190en_US

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