Rescuing Loading Induced Bone Formation at Senescence 英文参考文献.docVIP

下载本文档

5
0
约7.21万字
约 16页
2017-05-13 发布于上海
举报
版权申诉

Rescuing Loading Induced Bone Formation at Senescence 英文参考文献.doc

1、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。。
2、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。
3、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)。
4、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
5、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。
6、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。
7、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

Rescuing Loading Induced Bone Formation at Senescence 英文参考文献

RescuingLoadingInducedBoneFormationat Senescence SundarSrinivasan1*,BrandonJ.Ausk1,JitendraPrasad1,DewayneThreet1,StevenD.Bain1,ThomasS. Richardson2,TedS.Gross1 1Department of Orthopedics and Sports Medicine, University of Washington, Seattle, Washington, United States of America, 2Departmentof Statistics, University of Washington,Seattle,Washington,UnitedStatesofAmerica Abstract The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensivegiventheprevailingoverburdenedhealthcaresystems.Whilevigorousskeletalloadingisanabolicandholds promise, deficits in mechanotransduction accrued withage markedly diminish the efficacy ofreadily complied, exercise- basedstrategiestocombatosteoporosisintheelderly.Ourapproachtoexploreandcounteracttheseage-relateddeficits wasguidedbycellularsignalingpatternsacrosshierarchicalscalesandbytheinsightthatcellresponsesinitiatedduring transient,rare eventshold potentialtoexerthigh-fidelitycontrolovertemporallyandspatiallydistanttissueadaptation. 2+ Here,wepresentanagent-basedmodelofreal-timeCa /NFATsignalingamongstbonecellsthatfullydescribedperiosteal boneformationinducedbyawidevarietyofloadingstimuliinyoungandagedanimals.Themodelpredictedage-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that werepromisingtargetsfortherapy.Baseduponmodelpredictions,weimplementedaninvivointerventionandshowfor thefirsttimethatsupplementingmechanicalstimuliwithlow-doseCyclosporinAcancompletelyrescueloadinginduced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceuticalalongsidemildphysicalexerciseasaninexpensive,yetpotenttherapytoaugmentbonemassintheelderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli,andquantificationoftheseotherwiseinaccessible,transientev