Hepcidin基因敲除对小鼠骨代谢的影响及相关机制研究-豆柴文库

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Hepcidin基因敲除对小鼠骨代谢的影响及相关机制研究
Title:TheEffectsofHepcidinGeneKnockoutonBoneMetabolisminMiceandItsUnderlyingMechanisms
Abstract:
Hepcidin,akeyregulatorofironmetabolism,hasbeenrecentlyimplicatedintheregulationofbonehomeostasis.However,theexactconsequencesofhepcidingeneknockoutonbonemetabolisminmiceandtheunderlyingmechanismsremainunclear.Inthisstudy,weaimedtoinvestigatetheeffectsofhepcidingeneknockoutonbonemetabolisminmiceandexploretherelatedmechanisms.
Introduction:
Hepcidinisahepaticpeptidehormonethatplaysacrucialroleinregulatingironhomeostasis.Itisprimarilyknownforitsabilitytoinhibitironabsorptionintheintestineandironreleasefrommacrophages,therebycontrollingsystemicironlevels.Overthepastdecade,growingevidencehassuggestedtheinvolvementofhepcidininbonemetabolism.Emergingstudieshaveshownthathepcidinmayinfluencebonehealthdirectlythroughitsactiononosteoblastsandosteoclasts,aswellasindirectlybyaffectingironavailabilityinthebonemicroenvironment.However,thepreciseeffectsofhepcidingeneknockoutonbonemetabolismandtheunderlyingmechanismsarelargelyunclear.
Methods:
1.GenerationofHepcidinGeneKnockoutMice:
HepcidingeneknockoutmiceweregeneratedusingCRISPR/Cas9geneeditingtechnology.ThesuccessfulknockoutwasconfirmedbygenotypingandPCRanalysis.
2.EvaluationofBonePhenotype:
Bonephenotypes,includingbonemineraldensity,bonearchitecture,andboneturnovermarkers,wereassessedusingdual-energyX-rayabsorptiometry(DXA),micro-computedtomography(micro-CT),andenzyme-linkedimmunosorbentassays(ELISA),respectively.
3.WholeTranscriptomeAnalysis:
RNA-sequencing(RNA-seq)wasperformedonbonetissuesfromhepcidinknockoutandwild-typemicetoidentifydifferentiallyexpressedgenesandpathwaysrelatedtobonemetabolism.
4.QuantitativeReal-TimePCR(qRT-PCR):
qRT-PCRwasconductedtovalidatetheexpressionofselectedgenesofinterestidentifiedthroughRNA-seqanalysis.
Results:
Thehepcidingeneknockoutmiceexhibitedalterationsinbonephenotypecharacterizedbydecreasedbonemineraldensityandcompromisedbonearchitecture.Furthermore,boneturnovermarker