MicroRNA-145 Regulates Chondrogenic Differentiation of Mesenchymal Stem Cells by Targeting Sox9 英文参考文献.docVIP

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MicroRNA-145 Regulates Chondrogenic Differentiation of Mesenchymal Stem Cells by Targeting Sox9 英文参考文献.doc

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MicroRNA-145 Regulates Chondrogenic Differentiation of Mesenchymal Stem Cells by Targeting Sox9 英文参考文献

MicroRNA-145RegulatesChondrogenicDifferentiation ofMesenchymalStemCellsbyTargetingSox9 BoYang1,HongfengGuo1,YulanZhang1,2,LeiChen3,DajunYing1*,ShiwuDong1* 1LaboratoryofBiomechanics,DepartmentofAnatomy,TheThirdMilitaryMedicalUniversity,Chongqing,People’sRepublicofChina,2DepartmentofAnesthesiology, ChengduMilitaryGeneralHospital,Chengdu,People’sRepublicofChina,3DepartmentofOrthopaedics,SouthwestHospital,Chongqing,People’sRepublicofChina Abstract Chondrogenic differentiation of mesenchymal stem cells (MSCs) is accurately regulated by essential transcription factors andsignalingcascades.However,theprecisemechanismsinvolvedinthisprocess stillremaintobedefined.MicroRNAs (miRNAs)regulatevariousbiologicalprocessesbybindingtargetmRNAtoattenuateproteinsynthesis.Toinvestigatethe mechanisms for miRNAs-mediated regulation of chondrogenic differentiation, we identified that miR-145 was decreased during transforming growth factor beta 3 (TGF-b3)-induced chondrogenic differentiation of murine MSCs. Subsequently, dual-luciferasereportergeneassaydatademonstratedthatmiR-145targetsaputativebindingsiteinthe39-UTRofSRY- related high mobility group-Box gene 9 (Sox9) gene, the key transcription factor for chondrogenesis. In addition, over- expressionofmiR-145decreasedexpressionofSox9onlyatproteinlevelsandmiR-145inhibitionsignificantlyelevatedSox9 proteinlevels.Furthermore,over-expressionofmiR-145decreasedmRNAlevelsforthreechondrogenicmarkergenes,type II collagen (Col2a1), aggrecan (Agc1), cartilage oligomeric matrix protein (COMP), type IX collagen (Col9a2) and type XI collagen(Col11a1)inC3H10T1/2cellsinducedbyTGF-b3,whereasanti-miR-145inhibitorincreasedtheexpressionofthese chondrogenic marker genes. Thus, our studies demonstrated that miR-145 is a key negative regulator of chondrogenic differentiationbydirectlytargetingSox9atearlystageofchondrogenicdifferentiation. Citation:YangB,GuoH,ZhangY,ChenL,YingD,etal.(2011)MicroRNA-145RegulatesChondrogenicDifferentiationofMesenchymalStemCel