模拟微重力下骨髓间充质干细胞成骨分化潜能及分子机理研究

模拟微重力下骨髓间充质干细胞成骨分化潜能及分子机理研究摘要

骨髓间充质干细胞（BMSCs）在成骨分化中起着重要作用，而微重力对BMSCs的成骨分化潜能和分子机理影响尚不清楚，因此我们开展了模拟微重力下BMSCs成骨分化的相关研究。使用3DRotaryWallVesselbioreactor模拟微重力，在模拟微重力下培养BMSCs，采用ALP染色、电镜、转录组学和蛋白质组学等方法研究BMSCs的成骨分化潜能和分子机理。结果显示，模拟微重力下BMSCs的成骨分化潜能降低，同时转录组学和蛋白质组学的分析证实细胞分化相关基因和蛋白质有不同程度的异常表达。本研究结果不仅对微重力对BMSCs成骨分化的影响做出了初步探究，同时为进一步研究微重力下骨髓间充质干细胞的生命过程提供了新思路。

关键词：微重力；骨髓间充质干细胞；成骨分化；转录组学；蛋白质组学

Abstract

Bonemarrowmesenchymalstemcells(BMSCs)playanimportantroleinosteogenicdifferentiation.However,theeffectofmicrogravityontheirosteogenicdifferentiationpotentialandmolecularmechanismremainsunclear.Therefore,weconductedastudyontheosteogenicdifferentiationofBMSCsundersimulatedmicrogravity.Weused3DRotaryWallVesselbioreactortosimulatemicrogravity,cultivatedBMSCsundersimulatedmicrogravity,andusedALPstaining,electronmicroscopy,transcriptomics,andproteomicstoinvestigatetheosteogenicdifferentiationpotentialandmolecularmechanismofBMSCs.ResultsshowedthattheosteogenicdifferentiationpotentialofBMSCswasreducedundersimulatedmicrogravity,andthetranscriptomicsandproteomicsanalysisconfirmedabnormalexpressionofdifferentiationrelatedgenesandproteinstovaryingdegrees.ThisstudynotonlymakespreliminaryexplorationontheeffectofmicrogravityonBMSCsosteogenicdifferentiation,butalsoprovidesnewideasforfurtherstudyonthelifeprocessofBMSCsundermicrogravity.

Keywords：Microgravity；BoneMarrowMesenchymalStemCells；OsteogenicDifferentiation；Transcriptomics；ProteomicInrecentyears,researchontheeffectsofmicrogravityonbiologicalsystemshasattractedincreasingattention.Themicrogravityenvironmentinspacehasbeenfoundtohaveprofoundimpactsonthefunctionanddevelopmentofvarioustissuesandcells,includingbonemarrowmesenchymalstemcells(BMSCs).

BMSCsareatypeofmultipotentstemcellthatcandifferentiateintovariouscelltypes,includingosteoblasts,whichareresponsibleforboneformation.OsteogenicdifferentiationofBMSCsisacomplexprocessthatinvolvestheactivationofvarioussignalingpathwaysandtheexpressionofnumerousgenesandproteins.

ThestudyoftheeffectsofmicrogravityonBMSCsosteogenicdifferentiationhasimportantimplicationsforunderstandingthemechanismsunderlyingbonelossinastronautsanddevelopingeffectivecountermeasurestopreventit.

Inthisstudy,BMSCswereculturedundersimulatedmicrogravityconditionsusingarotarycellculturesystem,andtheirosteogenicdifferentiationwasevaluatedbymeasuringtheexpressionofvariousosteogenicmarkersandassessingtheirmineralizationcapacity.

TheresultsshowedthatsimulatedmicrogravitysignificantlyinhibitedtheosteogenicdifferentiationofBMSCs,asevidencedbyreducedexpressionofosteogenicmarkersanddecreasedmineralizationcapacity.Transcriptomicandproteomicanalysisfurtherrevealedabnormalexpressionofdifferentiation-relatedgenesandproteinsinBMSCsundermicrogravity.

ThesefindingssuggestthatmicrogravitycandisruptthenormalosteogenicdifferentiationprocessofBMSCs,whichmaycontributetobonelossinastronauts.Furtherstudiesareneededtoelucidatetheunderlyingmechanismsanddevelopeffectivecountermeasurestopreventit.

Inconclusion,thisstudyprovidesimportantinsightsintotheeffectsofmicrogravityonBMSCsosteogenicdifferentiationandhighlightstheneedforfurtherresearchinthisarea.ThetranscriptomicandproteomicanalysisusedinthisstudyalsoprovidesavaluableresourceforfuturestudiesonthelifeprocessesofBMSCsundermicrogravityInadditiontoboneloss,microgravityhasalsobeenshowntoaffectotherphysiologicalprocessesinthehumanbody,includingmuscleatrophy,changesincardiovascularfunction,andalterationsinimmunefunction.Theseeffectscanhaveseriousimplicationsforthehealthofastronautsduringlong-termspacemissions.

Tocounteractthesenegativeeffects,severalcountermeasureshavebeendeveloped,includingexerciseandnutritionalinterventions.Exercisehasbeenshowntobeeffectiveinmaintainingmuscleandbonemassinastronauts,whilenutritionalinterventionsaimtooptimizedietaryintaketomeettheuniqueneedsofindividualsinspace.

However,moreresearchisneededtofullyunderstandtheeffectsofmicrogravityonthehumanbodyandtodevelopmoreeffectivecountermeasures.Thiswillbeessentialasspacetravelandexplorationbecomemoreprevalentinthecomingyears,withlongermissionstothemoonandeventuallyMars.

Inconclusion,microgravityhasasignificantimpactonbonemetabolismandtheosteogenicdifferentiationofBMSCs.Furtherresearchisneededtobetterunderstandtheunderlyingmechanismsandtodevelopeffectivecountermeasurestopreventbonelossandotherphysiologicaleffectsofmicrogravity.ThisareaofresearchiscriticalforthesuccessandsafetyoffuturespacemissionsMicrogravityisnotonlycriticalforthesuccessandsafetyoffuturespacemissionsbutalsohasimportantimplicationsforhumanhealthonEarth.Forinstance,understandingthemechanismsunderlyingthebonelossassociatedwithmicrogravitycouldhelpdevelopnewtreatmentsforosteoporosis,adiseasecharacterizedbyreducedbonedensityandincreasedsusceptibilitytofractures.

Moreover,thephysiologicalchangescausedbymicrogravitymayhaveimplicationsforothersystemsinthebody,suchasthecardiovascular,immune,andnervoussystems.Forexample,studieshaveshownthatmicrogravitycanaltertheexpressionofgenesinvolvedintheimmuneresponse,potentiallyleadingtoimpairedimmunefunction.

Understandingtheeffectsofmicrogravityonhumanhealthisalsocrucialforcommercialspaceflight,whichisrapidlydevelopingasanewindustry.Withtheincreasingnumberofpeopletravelingtospacefortourism,research,orotherpurposes,thereisaneedtoensuretheirsafetyandwell-being.

Inadditiontoitsimplicationsforhumanhealth,microgravityalsohasmanyapplicationsinfieldssuchasmaterialsscience,fluiddynamics,andcombustionresearch.TheabsenceofgravityenablesresearcherstostudyphysicalandchemicalprocessesinwaysthatarenotpossibleonEarth,leadingtonewinsightsandinnovations.

Overall,microgravityisafascinatingandcomplexphenomenonwithfar-reachingimplicationsforhumanhealth,spaceexploration,andscientificresearch.Althoughmuchprogresshasbeenmadeinunderstandingitseffects,thereisstillmuchtolearn,and