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

doi:10.13701/j.cnki.kqyxyj.2020.12.017

口腔医学研究 ›› 2020, Vol. 36 ›› Issue (12): 1157-1161.DOI: 10.13701/j.cnki.kqyxyj.2020.12.017

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

戈杰, 周培培, 徐天舒, 朱志超, 杨旭^*

常州市第一人民医院口腔科江苏常州 213003

收稿日期:2020-05-12 出版日期:2020-12-28 发布日期:2020-12-28
通讯作者: *杨旭,E-mail:179873290@qq.com
作者简介:戈杰(1989~ ),男,江苏常州人,硕士,主治医师,研究方向:牙颌面组织再生修复。
基金资助:
常州市科技计划应用基础研究项目(编号:CJ20180060)

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

GE Jie, ZHOU Peipei, XU Tianshu, ZHU Zhichao, YANG Xu^*

Department of Stomatology, Changzhou First People's Hospital, Changzhou 213003, China

Received:2020-05-12 Online:2020-12-28 Published:2020-12-28

摘要/Abstract

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。

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

Abstract: 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 by β-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.

Key words: diabetes mellitus, insulin like growth factor 1, mesenchymal stem cells, cell aging, osteogenesis

戈杰, 周培培, 徐天舒, 朱志超, 杨旭. 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[J]. 口腔医学研究, 2020, 36(12): 1157-1161.

GE Jie, ZHOU Peipei, XU Tianshu, ZHU Zhichao, YANG Xu. IGF1 Participation in Bone Regeneration of Type 2 Diabetes Mellitus Patients through PI3K-AKT Signaling Pathway in Vitro[J]. Journal of Oral Science Research, 2020, 36(12): 1157-1161.

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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

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