Expression of Cartilage Developmental Genes in Hoxc8- and Hoxd4-Transgenic Mice 英文参考文献.docVIP

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Expression of Cartilage Developmental Genes in Hoxc8- and Hoxd4-Transgenic Mice 英文参考文献.doc

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Expression of Cartilage Developmental Genes in Hoxc8- and Hoxd4-Transgenic Mice 英文参考文献

ExpressionofCartilageDevelopmentalGenesinHoxc8- andHoxd4-TransgenicMice ClaudiaKruger1¤,ClaudiaKappen1,2¤* 1DepartmentofGenetics,CellBiology,andAnatomy,UniversityofNebraskaMedicalCenter,Omaha,Nebraska,UnitedStatesofAmerica,2CenterforHumanMolecular Genetics,Munroe-MeyerInstituteforGeneticsandRehabilitation,UniversityofNebraskaMedicalCenter,Omaha,Nebraska,UnitedStatesofAmerica Abstract Hox genes encode transcription factors, which regulate skeletal patterning and chondrocyte differentiation during the developmentofcartilage,theprecursortomaturebone.OverexpressionofthehomeoboxtranscriptionfactorsHoxc8and Hoxd4 causes severe cartilage defects due to delay in cartilage maturation. Matrix metalloproteinases (MMPs), bone morphogenetic proteins (BMPs) and fibroblastic growth factors (FGFs) are known to play important roles in skeletal development and endochondral bone formation and remodeling. In order to investigate whether these molecules are aberrantlyexpressedinHoxc8-and/orHoxd4-transgeniccartilage,weperformedquantitativeRT-PCRonchondrocytesfrom Hox-transgenicmice.GeneexpressionlevelsofBmp4,Fgf8,Fgf10,Mmp9,Mmp13,Nos3,Timp3,Wnt3aandWnt5awere altered in Hoxc8-transgenic chondrocytes, and Fgfr3, Ihh, Mmp8, and Wnt3a expression levels were altered in Hoxd4- transgenicchondrocytes,respectively.Notably,Wnt3aexpressionwaselevatedinHoxc8-andreducedinHoxd4-transgenic cartilage. These results suggest that both transcription factors affect cartilage maturation through different molecular mechanisms,andprovidethebasisforfuturestudiesintotheroleofthesegenesandpossibleinteractionsinpathogenesis ofcartilagedefectsinHoxc8-andHoxd4-transgenicmice. Citation:KrugerC,KappenC(2010)ExpressionofCartilageDevelopmentalGenesinHoxc8-andHoxd4-TransgenicMice.PLoSONE5(2):e8978.doi:10.1371/ journal.pone.0008978 Editor:FrankBeier,UniversityofWesternOntario,Canada ReceivedSeptember16,2009;AcceptedJanuary4,2010;PublishedFebruary2,2010 Copyright: ? 2010 Kruger, Kappen. This is an open-access article di