----校内链接----　　
同济就业网
同济招生网
----高校媒体----　　
北京大学新闻网
清华大学新闻网
南京大学新闻网
浙大求是新闻网
上海交大新闻网
中国科大新闻网
西安交大新闻网
复旦大学新闻网
华东师大新闻网
华东理工新闻网
上海财大新闻网
南开大学新闻网
天津大学新闻网
山东大学新闻网
中山大学新闻网
华南理工新闻网
兰州大学新闻网
吉林大学新闻网
中南大学新闻网
哈尔滨工业大学新闻网
上海外国语大学新闻网
----媒体链接----　　
上海教育新闻网
当前位置：首页
>> 媒体聚焦
Wnt7b信号转导 在骨发育中研究获成效
　　本报讯（李跃）由同济大学附属上海第十人民医院胡洪亮主持进行的“Wnt7b信号转导在骨发育中的作用和机理研究”近日获得了有关部门的认证。据了解，该项目由目前国内骨和软骨发育生物学方面的专家、美国NIH重大项目主要参与者、中国973项目参与者、现任上海第十医院检验中心实验室副主任胡洪亮领衔，由长期从事血液学研究并擅长骨髓片技术的专家、现交通大学附属瑞金医院主任医师胡翊群和从事蛋白质组学的研究、擅长Westernblot和动物实验的陈婷婷医生共同参与完成。& 　　据胡洪亮介绍，该项目是以兔骨髓基质干细胞为模式在体外进一步研究Wnt7b在成骨中的作用。具体地概述其机理，是将Wnt7b转染诱导的骨髓基质干细胞作为种子细胞构建组织工程骨以修复缺损部位，从组织化学、生物化学、生物力学等方面评价构建的组织工程骨，以进一步了解Wnt7b在体内局部构建组织中的作用。同时，以RosaA为载体将Wnt7b基因导入小鼠ES细胞，制备Wnt7b转基因小鼠，然后用原位杂交和组织化学技术分析Wnt7b体内过表达后的组织学变化，进一步明确Wnt7b在整体胚胎发育中的功能。& &&& &&&&&&&&&&&& 科技日报　　　
版权所有 同济大学 新闻中心 Copyright tongji university news center, 2012 E-mail:dxb@mail.&&Wnt-7 protein (IPR013300) & InterPro & EMBL-EBI
Your browser does not support JavaScript or you turned off JavaScript options. Some features on this website won't work properly ().
Domain architectures
Structures
Cross-references
Wnt-7 protein (IPR013300)
Short name:
Family relationships
(IPR005817)
Wnt-7 protein (IPR013300)
Description
Wnt proteins constitute a large family of secreted molecules that are involved in intercellular signalling during development. The name derives from the first 2 members of the family to be discovered: int-1 (mouse) and wingless (Drosophila) []. It is now recognised that Wnt signalling controls many cell fate decisions in a variety of different organisms, including mammals []. Wnt signalling has been implicated in tumourigenesis, early mesodermal patterning of the embryo, morphogenesis of the brain and kidneys, regulation of mammary gland proliferation and Alzheimer's disease [, ].
Wnt-mediated signalling is believed to proceed initially through binding to cell surface receptors of the signal is subsequently transduced through several cytoplasmic components to B-catenin, which enters the nucleus and activates the transcription of several genes important in
development []. Several non-canonical Wnt signalling pathways have also been elucidated that act independently of B-catenin. Canonical and noncanonical Wnt signaling branches are highly interconnected, and cross-regulate each other [].
Members of the Wnt gene family are defined by their sequence similarity to mouse Wnt-1 and Wingless in Drosophila. They encode proteins of ~350-400 residues in length, with orthologues identified in several, mostly vertebrate, species. Very little is known about the structure of
Wnts as they are notoriously insoluble, but they share the following features characteristics of secretory proteins:
a signal peptide, several potential N-glycosylation sites and 22 conserved cysteines [] that are probably involved in disulphide bonds. The Wnt proteins seem to adhere to the plasma membrane of the secreting cells and are therefore likely to signal over only few cell diameters. Fifteen major Wnt gene families have been identified in vertebrates, with multiple subtypes within some classes.
Wnt-7 cDNA was isolated from mouse using a PCR-based strategy, where it was found to be expressed in adult tissues, particularly in brain and lung [].
Two subtypes are known to exist, designated Wnt-7A and B. Wnt-7A has been implicated in development of the uterus,
Wnt-7B is believed to play a role in lung and placental development.
Biological Process
Wnt signaling pathway
multicellular organismal development
Molecular Function
receptor binding
Cellular Component
extracellular region
Contributing signatures
Signatures from InterPro member databases are used to construct an entry.
(WNT7PROTEIN)当前位置： >
WNT7B Promotes Bone Formation in part through
WNT7B Promotes Bone Formation in part through
WNT7BPromotesBoneFormationinpartthroughmTORC1
JianquanChen1,XiaolinTu2¤a,EmelEsen1,3,KyuSangJoeng2,3¤b,CongxinLin2,JeffreyM.Arbeit4,
¨egg5,MichaelN.Hall5,LiangMa2,3,6,FanxinLong1,2,3,6*MarkusA.Ru
1DepartmentofOrthopaedicSurgery,WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica,2DepartmentofMedicine,Washington
UniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica,3DivisionofBiologyandBiomedicalSciences,WashingtonUniversityinSt.Louis,St.Louis,Missouri,UnitedStatesofAmerica,4DepartmentofSurgery,WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica,5Biozentrum,UniversityofBasel,Basel,Switzerland,6DepartmentofDevelopmentalBiology,WashingtonUniversitySchoolofMedicine,St.Louis,Missouri,UnitedStatesofAmerica
WNTsignalinghasbeenimplicatedinbothembryonicandpostnatalboneformation.However,thepertinentWNTligandsandtheirdownstreamsignalingmechanismsarenotwellunderstood.ToinvestigatetheosteogeniccapacityofWNT7BandWNT5A,bothnormallyexpressedinthedevelopingbone,weengineeredmousestrainstoexpresseitherproteininaCre-dependentmanner.TargetedinductionofWNT7B,butnotWNT5A,intheosteoblastlineagedramaticallyenhancedbonemassduetoincreasedosteoblthisphenotypebeganinthelate-stageembryoandintensifiedpostnatally.Similarly,postnatalinductionofWNT7BinRunx2-lineagecellsgreatlystimulatedboneformation.WNT7BactivatedmTORC1throughPI3K-AKTsignaling.GeneticdisruptionofmTORC1signalingbydeletingRaptorintheosteoblastlineagealleviatedtheWNT7B-inducedhigh-bone-massphenotype.Thus,WNT7BpromotesboneformationinpartthroughmTORC1activation.
Citation:ChenJ,TuX,EsenE,JoengKS,LinC,etal.(2014)WNT7BPromotesBoneFormationinpartthroughmTORC1.PLoSGenet10(1):e1004145.doi:10.1371/journal.pgen.1004145
Editor:DavidR.Beier,SeattleChildren’sResearchInstitute,UnitedStatesofAmericaReceivedJune12,2013;AcceptedDecember12,2013;PublishedJanuary30,2014
Copyright:ss2014Chenetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.
Funding:TheworkwassupportedbygrantsR01ARDK065789(FL),R01ES(LM)andP30AR057235(WashingtonUniversityMusculoskeletalResearchCenter)fromNIAMS/NIH.Thefundershadnoroleinstudydesign,datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript.
CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist.*E-mail:longf@wudosis.wustl.edu
¤aCurrentaddress:DepartmentofAnatomyandCellBiology,IndianaUniversitySchoolofMedicine,Indianapolis,Indiana,UnitedStatesofAmerica.¤bCurrentaddress:DepartmentofMolecularandHumanGenetics,BaylorCollegeofMedicine,Houston,Texas,UnitedStatesofAmerica.
Introduction
WNTproteinsareafamilyofsignalingmoleculesthatcontrolcellproliferation,fatedecision,polarityandmigrationthroughoutmetazoanevolution[1].Byengagingvariousreceptorsandco-receptorsatthecellmembrane,theseproteinsactivateacontext-dependentintracellularsignalingnetworktoinducediversebiolog-icalresponses[2].DeregulationofWNTsignalingisfrequentlyassociatedwithhumandiseases[3].WNTsignalingwasfirstassociatedwithbonediseasesbythefindingthatloss-of-functionmutationsintheWNTco-receptorLRP5causeosteoporosis-pseudogliomasyndrome(OPPG)(Gongetal.,2001).Incontrast,deficiencyinthesecretedWNTinhibitorSOST,ormutationsinLRP5renderingitrefractorytotheWNTinhibitorssuchasSOSTorDKK1,resultsinhighbonemassinpatients[4,5,6,7,8,9].Inaddition,mutationsinWTX,aninhibitorofWNT/b-cateninsignaling,wereshowntocauseX-linkedsclerosingbonedysplasiaknownasOSCSinhumans[10,11].Inthemouse,deletionofLRP5eithergloballyorspecificallyinbonecausesosteopeniainthemouse[12,13],whereasexpressionofthehigh-bone-massformsofLRP5increasesboneaccrual[13,14].Moreover,micelackingoneDKK1alleleorbothSOSTallelesexhibitahigherbonemass[15,16].Overall,geneticevidencefrombothhumansandmicesupportstheimportanceofWNTsignalinginboneformation.
PLOSGenetics|www.plosgenetics.org
TheintracellularsignalingnetworkmediatingWNTfunctioninboneformationisnotcompletelyunderstood[17].Workinthemouseembryohasshownthatdeletionofb-catenin,orbothLRP5andLRP6,intheosteogenicprogenitorsabolishesosteoblastdifferentiation,indicatingthatb-cateninislikelyacriticalcomponentoftheWNTsignalingnetworkresponsibleforembryonicosteoblastogenesis[18,19,20,21,22].However,thesemicedieatbirth,andthereforearenotusefulforassessingwhetherornotb-cateninsimilarlymediatesWNTfunctioninpostnatalboneformation.Weandothershaverecentlyshownthatdeletionofb-catenininOsx-expressingcellsselectivelyinpostnatalmicereducedthelifespanandactivityofosteoblasts,aswellasincreasingadipogenesisinthebonemarrow[23,24].Besidesb-catenin,activationofPKCdorCAMKIIbyWNTthroughphosphatidylinositolsignalinghasalsobeenshowntopromoteosteoblastdifferentiation[25,26].Inaddition,multipleWNTligandshavebeenreportedtoactivatemTORC1(mammaliantargetofrapamycincomplex1)[27,28].WehaverecentlyshownthatWNTproteinsalsoactivatemTORC2tostimulateglycolysis[29].mTORC1differsfrommTORC2inthatituniquelycontainsRaptorandisacutelysensitivetorapamycin[30].BecausemTORC1signalingisacentralmechanismintegratingextracellularandintracellularcueswithanabolicmetabolism,itcouldpotentiallymediateWNTfunctionduringboneformation.
January2014|Volume10|Issue1|e1004145
Word文档免费下载：WNT7B Promotes Bone Formation in part through
（共13页）
wnt bone formation_基础医学_医药卫生_专业资料。Molecular...be examined in the latter part of this review....promotes dishevelleddependent LRP6 phosphorylation (...promotes bone formation while inactivation of the ...In addition, Wnt 7b deficiency led to defective ...Funding The reported work was supported in part ...