fgfr3在骨骼发育 稳态维持中的作用与相关机制分析word格式论文.docx

JNKC-Jun N-terminal kinasec-Jun 氨基末端激酶MMol/L摩尔/升mMonth月MinMinute分钟mmMillimetre毫米MMP13Matrixmetalloproteinase13基质金属蛋白酶13mRNAMessengerribonucleicacid信使核糖核酸MUT/MTMutant-type突变型OCOsteocalcin骨钙素PBSPhosphate-buffered salinesolution磷酸盐缓冲液PCRPolymerase chain reaction聚合酶链反应PFAParaformaldehyde多聚甲醛PKProtein K蛋白酶KPTHParathyroid hormone甲状旁腺素PTHrPParathyroid hormonerelated peptide甲状旁腺相关肽RNARibonucleic acid核糖核酸rpmRotation perminute转/分sSecond秒SDSSodium dodecylsulfate十二烷基磺酸钠ShhSonic hedgehogSonic豪猪蛋白STAT1Signaltransducerandactivatoroftranscription1转录活化蛋白1TDThanatophoricdysplasia致死性骨发育不全TETris-Hcl and EDTAbufferTris盐酸乙二胺四乙酸缓冲液TEMEDN,N,N,N’-tetramethylethylenediamine四氨基乙二胺TRAPTartrateresistant acid phosphatase抗酒石酸酸性磷酸酶WTWild-type野生型Therole andmechanismofFGFR3in skeleton development andhomeostasis?AbstractMutationsinthecodingsequenceoftheFGFR3genecancauseautosomaldominant humanskeletaldisorders,suchasachondroplasia(Ach),themostcommonformofdwarfism, thanatophoricdysplasia(TD)[1], and so on. Whileno effective clinical therapyis available for TDpatients,currenttreatmentsforACHpatientsaremainlygrowthhormonetreatmentand distraction osteogenesis,which havelimited effectwith manycomplications.FGFR3wasfoundtonegativelyregulateendochondralossification.Chenetalreported thatFGF-FGFR3signalingtargetsSTAT1/p21andIhhtoinhibitchondrocyteproliferation, whileFGF-FGFR3signalingandPTHrP/IHHsignalingmayinhibitchondrocytedifferentiation independently.YamanakafoundthatbothAch-(FGFR3G380R)andTDII-type(FGFR3 K650E)mutantFGFR3induceapoptosisandsignificantdecreaseofPTHrPexpressionin chondrogeniccellline.PTHrPtreatmentcanblunttheapoptoticresponseinducedbyFGFR3. UedasuggestedthatPTH1-34improvegrowthculturedbonefromACHmice,which indicatesthatPTH1-34maybeusedasapotentialtherapeuticagentforachondroplasia. However,theactualinvivoeffectofPTHsignalingontheskeletaldevelopmentofmice mimicking humanACH/TDanditsaction mechanismare stillnotfully clarified.The purpose ofthisstudywastoelucidatewhethertheinvivosystemicadminis