Runx2 Haploinsufficiency Ameliorates the Development of Ossification of the Posterior Longitudinal Ligament 英文参考文献.docVIP

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Runx2 Haploinsufficiency Ameliorates the Development of Ossification of the Posterior Longitudinal Ligament 英文参考文献.doc

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Runx2 Haploinsufficiency Ameliorates the Development of Ossification of the Posterior Longitudinal Ligament 英文参考文献

Runx2HaploinsufficiencyAmelioratestheDevelopment ofOssificationofthePosteriorLongitudinalLigament MakikoIwasaki1,JinyingPiao1,AyakoKimura2,ShingoSato1,HiroyukiInose1,HirokiOchi2, YoshinoriAsou1,KenichiShinomiya1,AtsushiOkawa1,ShuTakeda3* 1DepartmentofOrthopedicSurgery,TokyoMedicalandDentalUniversity,Tokyo,Japan,2HardTissueGenomeResearchCenter,TokyoMedicalandDentalUniversity, Tokyo,Japan,3SectionofNephrology,EndocrinologyandMetabolism,DepartmentofInternalMedicine,SchoolofMedicine,KeioUniversity,Tokyo,Japan Abstract OssificationofthePosteriorLongitudinalLigament(OPLL)isadiseasethatischaracterizedbytheectopiccalcificationofthe ligament;however,thepathogenesisofOPLLremainstobeinvestigated.WeattemptedtoidentifytheinvivoroleofRunx2, amasterregulatorofosteoblastdifferentiationandskeletalmineralization,inthepathogenesisofOPLL.Theexpressionof Runx2intheligamentwasexaminedusinginsituhybridizationandimmunohistochemistryandbymonitoringtheactivity ofaLacZgenethatwasinsertedintotheRunx2genelocus.ToinvestigatethefunctionalroleofRunx2,westudiedENPP1ttw/ ttwmice,amousemodelofOPLL,thatwerecrossedwithheterozygousRunx2micetodecreasetheexpressionofRunx2,and weperformedhistologicalandquantitativeradiologicalanalysesusing3D-microCT.Runx2wasexpressedintheligament ofwild-typemice.TheinductionofRunx2expressionprecededthedevelopmentofectopiccalcificationintheOPLL-like region of the ENPP1ttw/ttw mice. Runx2 haploinsufficiency ameliorated the development of ectopic calcification in the ENPP1ttw/ttw mice.Collectively,thisstudydemonstratedthatRunx2isexpressedinanOPLL-likeregion,anditselevationis aprerequisitefordevelopingthecompleteOPLL-likephenotypeinamousemodelofOPLL. Citation: Iwasaki M, Piao J, Kimura A, Sato S, Inose H, et al. (2012) Runx2 Haploinsufficiency Ameliorates the Development of Ossification of the Posterior LongitudinalLigament.PLoSONE7(8):e43372.doi:10.1371/journal.pone.0043372 Editor:EfratMonsonego-Ornan,TheHebrewUniversity,Israel ReceivedMarch9,2012;AcceptedJuly24,2012;Publis