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锌指蛋白521通过抑制Wnt/β-连环蛋白信号通路抑制大鼠间充质干细胞的成骨分化

[Zinc finger protein 521 suppresses osteogenic differentiation of rat mesenchymal stem cells by inhibiting the Wnt/beta-catenin signaling pathway].

作者信息

Xie X-T, Zhan X-L, Hu Z-H

机构信息

Spine and Osteopathy Ward The First Affiliated Hospital of Guangxi Medical University Nanning, Guangxi, 530021 China.

Department of Orthopedics Liuzhou Peoples Hospital Liuzhou, Guangxi, 545006 China.

出版信息

Mol Biol (Mosk). 2017 May-Jun;51(3):464-472. doi: 10.7868/S0026898417020215.

Abstract

Zinc finger protein 521 (Zfp521) is involved in a number of cellular processes in a variety of cells and tissues. In the present study, the effects of Zfp521 on osteogenic differentiation of rat mesenchymal stem cells (MSCs) were investigated. The results showed that, in rat MSCs, knocking down cellular Zfp521 by short hairpin RNA (shRNA) decreases cell proliferation while promoting ALP activity, calcium accumulation, and the expression of mRNA that encodes bone sialoprotein (BSP), osteocalcin (OCN) and Runx2. Furthermore, in Zfp521-depleted cells, the up-regulation of phospho-Wnt (p-Wnt) and beta-catenin expression levels was detected. However, over-expression of Zfp521 played the opposite role in proliferation and osteogenic differentiation of rat MSCs. To further demonstrate the functions of the Wnt/beta-catenin signaling in Zfp521 regulated-osteogenic differentiation, the activation of Wnt/beta-catenin was blocked with IWP-2 inhibitor. The suppression of the Wnt/beta-catenin pathway completely abrogated the effects of Zfp521 knockdown on osteogenic differentiation of rat MSCs. Therefore, we conclude that Zfp521 regulates osteogenic differentiation of rat MSCs through the suppression of the Wnt/beta-catenin signaling pathway.

摘要

锌指蛋白521(Zfp521)参与多种细胞和组织中的许多细胞过程。在本研究中,研究了Zfp521对大鼠间充质干细胞(MSCs)成骨分化的影响。结果表明,在大鼠MSCs中,通过短发夹RNA(shRNA)敲低细胞内Zfp521可降低细胞增殖,同时促进碱性磷酸酶(ALP)活性、钙积累以及编码骨唾液蛋白(BSP)、骨钙素(OCN)和Runx2的mRNA表达。此外,在Zfp521缺失的细胞中,检测到磷酸化Wnt(p-Wnt)和β-连环蛋白表达水平上调。然而,Zfp521的过表达在大鼠MSCs的增殖和成骨分化中发挥相反作用。为了进一步证明Wnt/β-连环蛋白信号在Zfp521调节的成骨分化中的功能,用IWP-2抑制剂阻断Wnt/β-连环蛋白的激活。Wnt/β-连环蛋白通路的抑制完全消除了Zfp521敲低对大鼠MSCs成骨分化的影响。因此,我们得出结论,Zfp521通过抑制Wnt/β-连环蛋白信号通路调节大鼠MSCs成骨分化。

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