Extracellular nicotinamide phosphoribosyltransferase (NAMPTvisfatin) inhibits insulin-like growth factor-1 signaling and proteoglycan synthesis in human articular chondrocytes.docVIP

下载本文档

5
0
约3.13万字
约 8页
2017-05-16 发布于上海
举报
版权申诉

Extracellular nicotinamide phosphoribosyltransferase (NAMPTvisfatin) inhibits insulin-like growth factor-1 signaling and proteoglycan synthesis in human articular chondrocytes.doc

1、本文档共8页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Extracellular nicotinamide phosphoribosyltransferase (NAMPTvisfatin) inhibits insulin-like growth factor-1 signaling and proteoglycan synthesis in human articular chondrocytes

YammaniandLoeserArthritisResearchTherapy2012,14:R23 /content/14/1/R23 RESEARCH ARTICLE OpenAccess Extracellularnicotinamide phosphoribosyltransferase(NAMPT/visfatin) inhibitsinsulin-likegrowthfactor-1signaling andproteoglycansynthesisinhuman articularchondrocytes RaghunathaRYammani*andRichardFLoeser Abstract Introduction:Obesityisoneofthemajorriskfactorsforthedevelopmentofosteoarthritis(OA).Althoughthe mechanicalfactorsappeartobecritical,recentstudieshavesuggestedaroleforadipokinesincartilage degradation.Chondrocytesfromosteoarthriticcartilagerespondpoorlytoinsulin-likegrowthfactor-1(IGF-1)and themolecularmechanism(s)involvedisnotclearlyunderstood.Thepurposeofthepresentstudywasto determinetheroleofextracellularnicotinamidephosphoribosyltransferase(eNAMPT/visfatin),anewlydescribed adipokine,inregulatingIGF-1functioninchondrocytes. Methods:HumanarticularchondrocytesisolatedfromnormalanklecartilagewerepretreatedwitheNAMPT(0.1to 5.0μg/ml)overnightfollowedbystimulationwithIGF-1(50ng/ml)for24hours,andproteoglycansynthesiswas measuredby[35S]sulfateincorporation.ChondrocyteswerepretreatedwitheNAMPTovernightfollowedbyIGF-1 for10minutes,andthecelllysateswereimmunoblottedforvarioussignalingproteinsthatareactivatedbyIGF-1 usingphosphospecificantibodies.Inaddition,chondrocyteswerepretreatedwithmitogen-activatedproteinkinase kinaseinhibitor(U0126)priortostimulationwitheNAMPTandIGF-1. Results:PretreatmentofchondrocyteswitheNAMPTinhibitedIGF-1-stimulatedproteoglycansynthesisinadose- dependentmanner.TreatmentofchondrocyteswitheNAMPTinhibitedIGF-1-inducedphosphorylationofsignaling molecules,includinginsulinreceptorsubstrate-1andAKT.Interestingly,pretreatmentofchondrocyteswith eNAMPTdidnotinhibitIGF-1-mediatedphosphorylationoftheIGF-1receptor;however,itstimulatedasustained phosphorylationoftheextracellularsignal-regulatedkinase(ERK)/mitogenactivatedproteinkinase(MAPK)signaling pathway.InhibitionoftheERK/MAPKsignalingpathwayrestoredIGF-1-mediatedinsulinreceptorsubstrate-1and AKTphos