FGF-signalling-regulates-bone-growth-through-autop

FGFsignallingregulatesbonegrowththroughautophagyLetterfromNaturePublishedDec,2015ReporterHFLTINTRODUCTIONSkeletalgrowthreliesonbothbiosyntheticandcatabolicprocesses.Autophagyisacatabolicprocessthatplaysafundamentalpartintissuehomeostasis.Weinvestigatedtheroleofautophagyduringbonegrowth,whichismediatedbychondrocyterateofproliferation,hypertrophicdifferentiationandextracellularmatrixdepositioningrowthplates.Cre-LoxP重组酶系统Cre-LoxP重组酶系统在新型基因打靶中获得广泛应用，是条件性基因打靶、诱导性基因打靶、时空特异性基因打靶策略的技术核心。CRE-LoxPinESCellsEXON1EXON2TARGETINGCONSTRUCTNEOTKEXON1EXON2GENEINESCELLCRE+EXON1EXON2NEOTKGENEINESCELLEXON2EXON1Crispr/Cas9系统CRISPR/Cas9是细菌和古细菌在长期演化过程中形成的一种适应性免疫防御，可用来对抗入侵的病毒及外源DNA。CRISPR-Cas技术是继锌指核酸酶（ZFN）、ES细胞打靶和TALEN等技术后可用于定点构建基因敲除大、小鼠动物的第四种方法。DETAIL•Prx1-CreandCol2a1-Cre:expresstheCreproteininthelimbmesenchymalcellsandinmaturechondrocytes,respectively.•CollagenFibres:胶原纤维•TypeIIProcollagen(PC2):II型前胶原•Fibroblastgrowthfactor(FGF):成纤维生长因子，其中已报到FGF-18可以通过FGFR-3促进软骨形成•Spautin-1:USP10和USP13特异性抑制剂•HSP47:热休克蛋白47，一种内质网特异性分子伴侣•Sec31:COPIImarker•Tat-beclin-1:重组蛋白beclin-1，Tat-穿膜肽RESULTSFig1.Autophagyregulatesthecompositionofgrowth-plateECMFig2.AutophagyregulatesPC2secretionduringchondrogenesisFig3.FGF18regulatesautophagyingrowth-platechondrocytesFGF18regulatesautophagyviaFGFR4andJNK1/2signallingFGF18regulatesautophagythroughbeclin-1complexactivation2xFYVE:又叫DFCP1,PI3P结合蛋白Fig4.FGF18regulatesCol2secretionviaautophagyCONCLUSION