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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.docx

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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