RNA转染(Entranster)与成骨细胞增殖和分化研究_图文.doc

Contents lists available at ScienceDirect Experimental Cell Research journal homepage: /locate/yexcr Liraglutide,a glucagon-like peptide-1receptor agonist,facilitates osteogenic proliferation and di ?erentiation in MC3T3-E1cells through phosphoinositide 3-kinase (PI3K/protein kinase B (AKT,extracellular signal-related kinase (ERK1/2,and cAMP/protein kinase A (PKAsignaling pathways involving β-catenin Xuelun Wu a ,b ,Shilun Li b ,Peng Xue a ,b ,Yukun Li a ,b , ? a Department of Endocrinology,The Third Hospital of Hebei Medical University,139Ziqiang Road,Shijiazhuang 050051,Hebei Province,PR China b Key Orthopaedic Biomechanics Laboratory of Hebei Province,139Ziqiang Road,Shijiazhuang 050051,Hebei Province,PR China A R T I C L E I N F O Keywords:GLP-1Osteoblast Proliferation Di ?erentiation Signaling pathway A B S T R A C T Previous studies have proven that glucagon-like peptide-1(GLP-1and its receptor agonist exert favorable anabolic e ?ects on skeletal metabolism.However,whether GLP-1could directly impact osteoblast-mediated bone formation is still controversial,and the underlying molecular mechanism remains to be elucidated.Thus in this paper,we investigated the e ?ects of liraglutide,a glucagon-like peptide-1(GLP-1receptor agonist,on murine MC3T3-E1preosteoblasts proliferation and di ?erentiation and explored the potential cellular basis.Our study con ?rmed the presence of GLP-1R in MC3T3-E1,and demonstrated that liraglutide promotes osteoblasts proliferation at an intermediate concentration (100nMand time (48h,upregulated the expression of osteo-blastogenic biomarkers at various stages,and stimulated osteoblastic mineralization.Liraglutide also elevated the intracellular cAMP level and phosphorylation of AKT,ERK and β-catenin simultaneously with increased nuclear β-catenin content and transcriptional activity.Pretreatment of cells with the inhibitors LY294002,PD98059,H89and GLP-1R and β-catenin siRNA partially blocked the liraglutide-induced signaling activat