IRS-1/TAZ信号通路对骨髓脂肪化的影响及机制  

Effect of IRS-1/TAZ signaling on bone marrow lipogenesis and the mechanism

作　　者：王娜[1] 刘畅 薛鹏[1] WANG Xiao 李玉坤[1] 刘斯静[3] WANG Na;LIU Chang;XUE Peng;WANG Xiao;LI Yu-kun;LIU Si-jing(Department of Endocrinology, the Third Hospital of Hebei Medical University, Key Orthopaedic Biomechanics Laboratory of Hebei Province, Shijiazhuang 050051, China;Center for Musculoskeletal Research, Johns Hopkins University, the United States of America, Maryland 21212,America;Department of Editorial, Hebei Medical University, Shijiazhuang 050017, China)

机构地区：[1]河北医科大学第三医院内分泌科,河北省骨科生物力学重点实验室,河北石家庄050051 [2]约翰·霍普金斯医学院肌肉与骨骼研究中心,美国马里兰21212 [3]河北医科大学期刊社,河北石家庄050017

出　　处：《河北医科大学学报》2020年第11期1251-1255,F0003,共6页Journal of Hebei Medical University

基　　金：河北省“三三三人才工程”培养项目(A2017003079);京津冀基础研究合作专项(19JCZDJC65500Z);河北省医学适用技术跟踪项目(G2019008);骨质疏松和骨矿盐疾病中青年医生优才培养计划暨白求恩·石药骨质疏松科研基金项目(GX20191107);河北省政府资助专科能力建设和专科带头人培养项目(361005)。

摘　　要：目的探讨胰岛素受体底物1(insulin receptor substrate 1,IRS-1)/具有盘状同源区域结合序列的转录共活化因子(transcriptional coactivator with PDZ-binding motif,TAZ)信号通路对大鼠骨髓间充质干细胞(bone marrow derived mesenchymal stem cells,BMSCs)成脂分化的影响。方法动物实验部分,采用苏木精和伊红(hematoxylin and eosin,HE)染色和免疫荧光染色比较对照组、假手术组、去卵巢手术(ovariectomy,OVX)组大鼠股骨内脂肪细胞计数,应用酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)3组大鼠股骨内IRS-1浓度;细胞实验部分,应用质粒转染技术对IRS-1和TAZ的表达进行干预,采用油红O染色和Western blot分析脂滴形成和成脂分化相关蛋白表达。结果OVX组大鼠股骨内脂肪细胞计数明显增多(P<0.05),股骨内IRS-1浓度明显降低(P<0.05);IRS-1表达上调可以增加TAZ的蛋白表达,减少抗CCAAT/增强子结合蛋白β(CCAAT/enhancer binding proteinβ,C/EBPβ)、过氧化物酶体增生物激活受体γ(peroxisome proliferator activated receptorγ,PPARγ)的蛋白表达,从而抑制BMSCs向脂肪细胞分化;敲除IRS-1或TAZ可以促进BMSCs向脂肪细胞分化。结论IRS-1通过上调TAZ表达,抑制BMSCs向脂肪细胞分化,IRS-1/TAZ信号可能作为控制骨质疏松症骨髓脂肪化的重要靶点。Objective To explore the influence of insulin receptor substrate 1(IRS-1)/transcriptional coactivator with PDZ-binding motif(TAZ)signaling on the adipogenic differentiation of bone marrow derived mesenchymal stem cells(BMSCs).Methods In vivo,the adipocyte count of rat femurs in control group,sham group and ovariectomy(OVX)group was analyzed by hematoxylin and eosin(HE)staining and immunofluorescence assay,and the IRS-1 concentration in rat femurs was tested by enzyme-linked immunosorbent assay(ELISA).In vitro,the plasmid transfection was used to change the IRS-1 and TAZ expression in BMSCs,the oil red O staining and western blot was used to analyze the lipid droplets and the expression of the adipogenic differentiation related proteins.Results The adipocyte count and the IRS-1 concentration in rat femurs in OVX group was significantly reduced.High expression of IRS-1 in BMSCs increased the expression of TAZ protein,and decreased the expression of CCAAT/enhancer binding proteinβ(C/EBPβ)and peroxisome proliferator activated receptorγ(PPARγ)proteins,which inhibited the adipogenic differentiation of BMSCs.Knockout of IRS-1 or TAZ promoted the adipogenic differentiation of BMSCs.Conclusion IRS-1 increased the TAZ expression,which inhibited the adipogenic differentiation of BMSCs.IRS-1/TAZ signaling in stem cells might be a new target to control the bone marrow lipogenesis of osteoporosis patients.

关 键 词：骨质疏松 骨髓间充质干细胞 胰岛素受体底物1 

分 类 号：R681[医药卫生—骨科学]