Sox9 Transcriptionally Represses Spp1 to Prevent Matrix Mineralization in Maturing Heart Valves and Chondrocytes 英文参考文献.docVIP

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Sox9 Transcriptionally Represses Spp1 to Prevent Matrix Mineralization in Maturing Heart Valves and Chondrocytes 英文参考文献.doc

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Sox9 Transcriptionally Represses Spp1 to Prevent Matrix Mineralization in Maturing Heart Valves and Chondrocytes 英文参考文献

Sox9TranscriptionallyRepressesSpp1toPreventMatrix MineralizationinMaturingHeartValvesand Chondrocytes JacquelineD.Peacock1.,DanielleJ.Huk1,2.,HasiniN.Ediriweera3,JoyLincoln2,4,5* 1MolecularandCellularPharmacologyGraduateProgram,LeonardM.MillerSchoolofMedicine,UniversityofMiami,Miami,Florida,UnitedStatesofAmerica,2Centerof CardiovascularandPulmonaryResearch,TheResearchInstituteatNationwideChildren’sHospital,DepartmentofPediatrics,TheOhioStateUniversity,Columbus,Ohio, United States of America, 3Medical Education, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States of America, 4Department of MolecularandCellularPharmacology, LeonardM.MillerSchoolofMedicine,UniversityofMiami,Miami,Florida,UnitedStatesofAmerica, 5DepartmentofMedicine, LeonardM.MillerSchoolofMedicine,UniversityofMiami,Miami,Florida,UnitedStatesofAmerica Abstract Sox9isanSRY-relatedtranscriptionfactorrequiredforexpressionofcartilaginousgenesinthedevelopingskeletalsystem andheart valvestructures.Incontrasttopositivelyregulatingcartilaginous matrix, Sox9alsonegativelyregulatesmatrix mineralization associated with bone formation. While the transcriptional activation of Sox9 target genes during chondrogenesishasbeencharacterized,themechanismsbywhichSox9repressesosteogenicprocessesarenotsoclear. Using ChIP-on-chip and luciferase assays we show that Sox9 binds and represses transactivation of the osteogenic glycoprotein Spp1. In addition, Sox9 knockdown in post natal mouse heart valve explants and rib chondrocyte cultures promotesSpp1expressionandmatrixmineralization,whileattenuatingexpressionofcartilagegenesTypeIICollagenand CartilageLinkProtein.Further,weshowthatSpp1isrequiredformatrixmineralizationinducedbySox9knockdown.These studiesprovideinsightsintothemolecularmechanismsbywhichSox9preventspathologicmatrixmineralizationintissues thatmustremaincartilaginous. Citation:PeacockJD,HukDJ,EdiriweeraHN,LincolnJ(2011)Sox9TranscriptionallyRepressesSpp1toPreventMatr