IGF1通过PI3K-AKT通路调控2型糖尿病患者颌骨改建的体外机制研究  

IGF1 Participation in Bone Regeneration of Type 2 Diabetes Mellitus Patients through PI3K-AKT Signaling Pathway in Vitro

作　　者：戈杰 周培培 徐天舒[1] 朱志超[1] 杨旭[1] GE Jie;ZHOU Peipei;XU Tianshu;ZHU Zhichao;YANG Xu(Department of Stomatology, Changzhou First People's Hospital, Changzhou 213003, China)

机构地区：[1]常州市第一人民医院口腔科,江苏常州213003

出　　处：《口腔医学研究》2020年第12期1157-1161,共5页Journal of Oral Science Research

基　　金：常州市科技计划应用基础研究项目(编号:CJ20180060)。

摘　　要：目的:探讨胰岛素样生长因子1(IGF1)调控2型糖尿病(T2DM)患者颌骨改建的体外生物学机制。方法:采用酶联免疫吸附试验(ELISA)方法比较T2DM患者与健康人血清IGF1差异;采用衰老染色比较健康人骨髓间充质干细胞(BMSC)、T2DM患者BMSC(DM-BMSC)衰老差异;Western blot方法比较BMSC、DM-BMSC成骨及PI3K-AKT通路表达差异;并在DM-BMSC中加入IGF1、AKT抑制剂进一步比较其衰老、成骨及PI3K-AKT通路表达差异。结果:T2DM患者血清IGF1显著低于健康人(P<0.05);正常培养3代后,衰老的DM-BMSC较BMSC更多(P<0.001),而DM-BMSC活化的p-PI3K、p-AKT表达显著弱于BMSC;成骨诱导后,DM-BMSC的骨指标OPN、OSX、RUNX2的表达同样低于BMSC;在DM-BMSC中加入IGF1后,相较于同时加入AKT抑制剂的实验组及未加任何刺激的对照组,其衰老细胞减少,活化的p-PI3K、p-AKT升高(P<0.05),OPN、OSX、RUNX2表达升高(P<0.05)。结论:T2DM患者血清IGF1剂量不足通过影响PI3K-AKT通路导致DM-BMSC易衰老,成骨能力减低,影响其颌骨改建。Objective:To investigate the mechanism of insulin like growth factor 1(IGF1)in bone regeneration of type 2 diabetes mellitus(T2DM)patients in vitro.Methods:Human IGF1 ELISA TABLE was used to detect the IGF1 levels of serum between normal and T2DM patients.The difference of senescence phenotype between normal bone mesenchymal stem cells(BMSC)and T2DM BMSC(DM-BMSC)was detected byβ-galactosidase senescence staining.The expression of osteogenic proteins and PI3K-AKT signaling pathway was investigated using western blotting analysis.To further illustrate the characters of senescence,osteogenesis,and PI3K-AKT signaling pathway expression,IGF1 and AKT inhibitor were added to DM-BMSC culture medium.Results:ELISA analysis showed that serum level of IGF1 was deficient in T2DM(P<0.05).The number of senescent DM-BMSC was more than that of BMSC(P<0.001).Western blotting indicated that DM-BMSC exhibited insufficient ability of osteogenesis and PI3K-AKT signaling pathway expression compared to BMSC.After cultured with IGF1,the number of senescent DM-BMSC decreased while the expression of osteogenesis markers and PI3K-AKT signaling pathway increased.However,AKT inhibitor restrained this function of IGF1.Conclusion:Lack of IGF1 leads to senescence of DM-BMSC and deficient osteogenic ability through PI3K-AKT signaling pathway in vitro which may affect bone regeneration of type 2 diabetes mellitus patients.

关 键 词：糖尿病 胰岛素样生长因子1 间质干细胞 细胞衰老 骨生成 

分 类 号：R58[医药卫生—内分泌]