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蛋白质组学分析揭示Grb2是软骨细胞周期性机械应力转导的关键调节因子。

Proteomic Analysis Reveals Grb2 as a Key Regulator of Periodic Mechanical Stress Transduction in Chondrocytes.

作者信息

Xu Shun, Li Zeng, Wang Zhen, Zhai Chenjun, Liang Wenwei, Zhu Chunhui, Fan Weimin

出版信息

Cell Physiol Biochem. 2017;44(4):1509-1525. doi: 10.1159/000485646. Epub 2017 Dec 4.

Abstract

BACKGROUND/AIMS: Periodic mechanical stress could significantly promote chondrocyte proliferation and matrix synthesis. However, the mechanisms underlying the ability of chondrocyte detecting and responding to periodic mechanical stimuli have not been well delineated.

METHODS

Quantitative proteomic analysis was performed to construct the differently expressed proteome profiles of chondrocyte under pressure. Then a combination of Western blot, quantitative real-time PCR, lentiviral vector and histological methods were used to confirm the proteomic results and investigate the mechanoseing mechanism.

RESULTS

Growth factor receptor-bound protein 2 (Grb2), a component of integrin adhesome, was found a 1.49-fold increase in dynamic stress group. This process was mediated through integrin β1, leading to increased phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1/2 (ERK1/2) respectively and then produce the corresponding biological effects.

CONCLUSION

This was the first time to demonstrate Grb2 has such an important role in periodic mechanotransduction, and the proteomic data could facilitate the further investigation of chondrocytes mechanosensing.

摘要

背景/目的:周期性机械应力可显著促进软骨细胞增殖和基质合成。然而,软骨细胞检测和响应周期性机械刺激的能力背后的机制尚未得到很好的阐明。

方法

进行定量蛋白质组学分析以构建受压软骨细胞的差异表达蛋白质组图谱。然后结合蛋白质印迹、定量实时聚合酶链反应、慢病毒载体和组织学方法来证实蛋白质组学结果并研究机械传感机制。

结果

生长因子受体结合蛋白2(Grb2),整联蛋白黏附体的一个组成部分,在动态应力组中发现增加了1.49倍。这个过程是通过整联蛋白β1介导的,分别导致粘着斑激酶(FAK)和细胞外信号调节激酶1/2(ERK1/2)的磷酸化增加,然后产生相应的生物学效应。

结论

这是首次证明Grb2在周期性机械转导中具有如此重要的作用,并且蛋白质组学数据有助于进一步研究软骨细胞的机械传感。

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