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氟芬那酸通过拮抗PI3K/AKT信号通路抑制间充质干细胞的成脂分化。

Flufenamic Acid Inhibits Adipogenic Differentiation of Mesenchymal Stem Cells by Antagonizing the PI3K/AKT Signaling Pathway.

作者信息

Liu Xuenan, Li Zheng, Liu Hao, Zhu Yuan, Xia Dandan, Wang Siyi, Gu Ranli, Zhang Ping, Liu Yunsong, Zhou Yongsheng

机构信息

Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Beijing 100081, China.

Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871, China.

出版信息

Stem Cells Int. 2020 Mar 16;2020:1540905. doi: 10.1155/2020/1540905. eCollection 2020.

Abstract

OBJECTIVES

Flufenamic acid (FFA) is a representative of the fenamic acids, an important group of NSAIDs. In the present study, we study the effects of FFA on adipogenesis of human mesenchymal stem cells (MSCs) and we explore the potential mechanism.

METHODS

To investigate the effects of FFA on adipogenic differentiation of hMSCs, human adipose-derived stem cells (hASCs) and human bone marrow mesenchymal stem cells (hBMMSCs), representative of hMSCs, were treated with FFA during adipogenic differentiation . The effects of FFA were evaluated using a heterotopic adipose formation assay in nude mice as well as ovariectomized (OVX) and aged mice. To explore the mechanism of FFA, Western blot was used to determine activation of the PI3K/AKT signaling pathway.

RESULTS

Our results demonstrate that, at certain concentrations, FFA inhibited adipogenesis of human MSCs both and . Mechanistically, FFA inhibited adipogenesis of human MSCs by inhibiting the PI3K/AKT pathway.

CONCLUSIONS

The present study indicated that FFA could be used to inhibit adipogenesis of human MSCs in tissue engineering and diseases related to excessive adipogenic differentiation of MSCs.

摘要

目的

氟芬那酸(FFA)是灭酸类药物的代表,灭酸类是一类重要的非甾体抗炎药。在本研究中,我们研究了FFA对人间充质干细胞(MSCs)成脂分化的影响,并探讨其潜在机制。

方法

为研究FFA对hMSCs成脂分化的影响,在成脂分化过程中用FFA处理人脂肪来源干细胞(hASCs)和人骨髓间充质干细胞(hBMMSCs),这两种细胞均为hMSCs的代表类型。通过在裸鼠以及去卵巢(OVX)小鼠和老龄小鼠中进行异位脂肪形成试验来评估FFA的作用。为探究FFA作用机制,采用蛋白质免疫印迹法检测PI3K/AKT信号通路的激活情况。

结果

我们的结果表明,在一定浓度下,FFA在体内和体外均抑制人MSCs的成脂分化。从机制上来说,FFA通过抑制PI3K/AKT通路来抑制人MSCs的成脂分化。

结论

本研究表明,FFA可用于在组织工程以及与MSCs过度成脂分化相关疾病中抑制人MSCs的成脂分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b517/7102471/311dfc433393/SCI2020-1540905.001.jpg

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