Neuropeptide Y Knockout Mice Reveal a Central Role of NPY in the Coordination of Bone Mass to Body Weight 英文参考文献.docVIP

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Neuropeptide Y Knockout Mice Reveal a Central Role of NPY in the Coordination of Bone Mass to Body Weight 英文参考文献.doc

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Neuropeptide Y Knockout Mice Reveal a Central Role of NPY in the Coordination of Bone Mass to Body Weight 英文参考文献

NeuropeptideYKnockoutMiceRevealaCentralRoleof NPYintheCoordinationofBoneMasstoBodyWeight PaulA.Baldock1,8,NicolaJ.Lee2,FrankDriessler1,ShuLin2,SusanAllison1,BernhardStehrer2,En-JuD. Lin3,LeiZhang2,RonaldF.Enriquez1,IrisP.L.Wong1,MichelleM.McDonald4,MatthewDuring5, DominiqueD.Pierroz6,KatySlack2,YanC.Shi2,ErnieYulyaningsih2,AygulAljanova2,DavidG.Little4, SergeL.Ferrari6,AmandaSainsbury2,7,JohnA.Eisman1,HerbertHerzog2,8* 1Osteoporosisand BoneBiology Program, GarvanInstitute ofMedicalResearch,StVincent’s Hospital, Sydney,Australia, 2Neuroscience Program,GarvanInstitute of MedicalResearch,StVincent’sHospital,Sydney,Australia,3DepartmentofPhysiologyandBiophysics,GeorgetownUniversityMedicalCenter,Washington,D.C.,United States of America, 4Department of Orthopaedic Research and Biotechnology, The Children’s Hospital at Westmead, Sydney, Australia, 5Department of Molecular MedicineandPathology,UniversityofAuckland,Auckland,NewZealand,6ServiceandLaboratoryofBoneDiseases,DepartmentofRehabilitationandGeriatrics,Faculty ofMedicine,GenevaUniversityHospital,Geneva,Switzerland,7SchoolofMedicalSciences,UniversityofNewSouthWales,Sydney,NewSouthWales,Australia,8Faculty ofMedicine,UniversityofNewSouthWales,Sydney,NewSouthWales,Australia Abstract Changesinwholebodyenergylevelsarecloselylinkedtoalterationsinbodyweightandbonemass.Here,weshowthat hypothalamic signals contribute to the regulation of bone mass in a manner consistent with the central perception of energy status. Mice lacking neuropeptide Y (NPY), a well-known orexigenic factor whose hypothalamic expression is increasedinfasting,havesignificantlyincreasedbonemassinassociationwithenhancedosteoblastactivityandelevated expressionofboneosteogenictranscriptionfactors,Runx2andOsterix.Incontrast,wildtypeandNPYknockout(NPY 2/2 ) miceinwhichNPYisspecificallyoverexpressedinthehypothalamus(AAV-NPY+)showasignificantreductioninbonemass despitedevelopinganobesephenotype.TheAAV-NPY+inducedlossofbonemassisconsistentwithmodelsk