p107 and p130 Coordinately Regulate Proliferation, Cbfa1 Expression, and Hypertrophic Differentiation during Endochondral Bone Development

Developmental Biology

Henry M. Kronenberg¹  Ferdinand Rossi¹  Helen E. MacLean¹  Ekaterina Semenova¹  Wei Yuan¹  Carol S. Lin¹  Richard O. Francis¹  David Cobrinik¹ 

[1] Departments of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, 10032

关键词: chondrocyte;    chondrogenesis;    p107;    p130;    hypertrophic differentiation;    Cbfa1;   

DOI  :  10.1006/dbio.2002.0691

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Duringendochondralbonedevelopment,boththechondrogenicdifferentiationofmesenchymeandthehypertrophicdifferentiationofchondrocytescoincidewiththeproliferativearrestofthedifferentiatingcells.However,themechanismsbywhichdifferentiationiscoordinatedwithcellcyclewithdrawal,andtheimportanceofthiscoordinationforskeletaldevelopment,havenotbeendefined.ThroughanalysisofmicelackingthepRB-relatedp107andp130proteins,wefoundthatp107wasrequiredinprechondrogeniccondensationsforcellcyclewithdrawalandforquantitativelynormalα1(II)collagenexpression.Remarkably,thep107-dependentproliferativearrestofmesenchymalcellswasnotneededforqualitativechangesthatareassociatedwithchondrogenicdifferentiation,includingproductionofAlcianblue-stainingmatrixandexpressionofthecollagenIIBisoform.Inchondrocytes,bothp107andp130contributedtocellcycleexit,andp107andp130losswasaccompaniedbyderegulatedproliferation,reducedexpressionofCbfa1,andreducedexpressionofCbfa1-dependentgenesthatareassociatedwithhypertrophicdifferentiation.Moreover,Cbfa1wasdetected,andhypertrophicdifferentiationoccurred,onlyinchondrocytesthathadundergoneorwereundergoingaproliferativearrest.TheresultssuggestthatCbfa1linksap107-andp130-mediatedcellcyclearresttochondrocyteterminaldifferentiation.

【 授权许可】

Unknown