Developmental Biology | |
The Wnt Antagonist Frzb-1 Regulates Chondrocyte Maturation and Long Bone Development during Limb Skeletogenesis | |
Philippa H. Francis-West1  Motomi Enomoto-Iwamoto1  Naoko Kanatani1  Yoshihiro Tamamura1  Hiroshi Okada1  Eiki Koyama1  Changshan Wu1  Jirouta Kitagaki1  Toshihisa Komori1  Tsutomu Nohno1  Toshiyuki Yoneda1  Vicki Church1  Masahiro Iwamoto1  Maurizio Pacifici1  Kojiro Kurisu1  Tatsuya Koike1  | |
[1] Departments of Molecular, Cell and Tumor Biology, Osaka University Faculty of Dentistry, Suita, Osaka, 565-0871, Japan | |
关键词: Wnt signaling; Frzb-1; chondrocyte maturation; matrix mineralization; endochondral ossification; limb development; | |
DOI : 10.1006/dbio.2002.0802 | |
学科分类:生物科学(综合) | |
来源: Academic Press | |
【 摘 要 】
TheWntantagonistFrzb-1isexpressedduringlimbskeletogenesis,butitsrolesinthiscomplexmultistepprocessarenotfullyunderstood.Toaddressthisissue,wedeterminedFrzb-1geneexpressionpatternsduringchicklongbonedevelopmentandcarriedoutgain-andloss-of-functionstudiesbymisexpressionofFrzb-1,Wnt-8(aknownFrzb-1target),ordifferentformsoftheintracellularWntmediatorLEF-1indevelopinglimbsandculturedchondrocytes.Frzb-1expressionwasquitestronginmesenchymalprechondrogeniccondensationsandthencharacterizedepiphysealarticularchondrocytesandprehypertrophicchondrocytesingrowthplates.VirallydrivenFrzb-1misexpressioncausedshorteningofskeletalelements,jointfusion,anddelayedchondrocytematuration,withconsequentinhibitionofmatrixmineralization,metalloproteaseexpression,andmarrow/boneformation.Ingoodagreement,misexpressionofFrzb-1oradominant-negativeformofLEF-1inculturedchondrocytesmaintainedthecellsatanimmaturestage.Instead,misexpressionofWnt-8oraconstitutivelyactiveLEF-1stronglypromotedchondrocytematuration,hypertrophy,andcalcification.ImmunostainingrevealedthatthedistributionofendogenousWntmediatorβ-cateninchangesdramaticallyinvivoandinvitro,fromlargelycytoplasmicinimmatureproliferatingandprehypertrophicchondrocytestonuclearinhypertrophicmineralizingchondrocytes.MisexpressionofFrzb-1preventedβ-cateninnuclearrelocalizationinchondrocytesinvivoorinvitro.ThedatademonstratethatFrzb-1exertsastronginfluenceonlimbskeletogenesisandisapowerfulanddirectmodulatorofchondrocytematuration,phenotype,andfunction.Phasesofskeletogenesis,suchasterminalchondrocytematurationandjointformation,appeartobeparticularlydependentonWntsignalingandthusverysensitivetoFrzb-1antagonisticaction.
【 授权许可】
Unknown
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201912090729306ZK.pdf | 116KB | download |