Atsttrin Promotes Cartilage Repair Primarily Through TNFR2-Akt Pathway.

Atsttrin Promotes Cartilage Repair Primarily Through TNFR2-Akt Pathway.
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Atsttrin 主要通过 TNFR2-Akt 途径促进软骨修复。

DOI:
10.3389/fcell.2020.577572
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发表时间:
2020
影响因子:
5.5
通讯作者:
Liu C
Liu C
中科院分区:
生物学2区
文献类型:
--
作者:
Wei J;Wang K;Hettinghouse A;Liu C

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软骨缺损造成了巨大的经济和人文负担,并构成了一个重要的临床问题。软骨修复的临床方法的功效通常是不足的,部分原因是软骨细胞的增殖能力有限。分子具有促进多能间充质干细胞向软骨细胞分化的能力,并且还可以获得修复受损软骨的能力。本研究旨在探讨Atsttrin(progranulin-derived engineered protein)在软骨修复中的作用及其信号通路。原代和间充质干细胞系用于微团培养。使用小鼠软骨缺损模型来确定Atsttrin在体内软骨修复中的作用。实时聚合酶链反应和蛋白质印迹分析用于监测Atsttrin对关键合成代谢和分解代谢信号分子的转录和蛋白质水平的影响。Atsttrin在体外刺激软骨形成,在体内加速软骨修复。此外,Atsttrin介导的软骨修复主要通过肿瘤坏死因子受体2启动的Akt信号和下游JunB转录因子发生。Atsttrin可能是一种有前途的软骨再生治疗方法。
Cartilage defects account for substantial economic and humanistic burdens and pose a significant clinical problem. The efficacy of clinical approaches to cartilage repair is often inadequate, in part, owing to the restricted proliferative capacity of chondrocytes. Molecules have the capacity to promote the differentiation of multipotent mesenchymal stem cells into chondrocytes and may also gain the ability to repair the damaged cartilage. This study aimed to investigate the role of Atsttrin (progranulin-derived engineered protein) in cartilage repair as well as the signaling pathway involved. Primary and mesenchymal stem cell lines were used for the micromass culture. A murine cartilage defect model was used to determine the role of Atsttrin in cartilage repair in vivo. Real-time polymerase chain reaction and Western blot analysis were used to monitor the effect of Atsttrin on the transcriptional and protein levels, respectively, of key anabolic and catabolic signaling molecules. Atsttrin stimulated chondrogenesis in vitro and accelerated cartilage repair in vivo. In addition, Atsttrin-mediated cartilage repair occurred primarily through tumor necrosis factor receptor 2-initiated Akt signaling and downstream JunB transcription factor. Atsttrin might serve as a promising therapeutic modality for cartilage regeneration.
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