SDF-1/CXCR4 axis promotes osteogenic differentiation of BMSCs through the JAK2/STAT3 pathway.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2021-01-01 Epub Date: 2021-09-28 DOI:10.5603/FHC.a2021.0020

Wen Xiong, Xin Guo, Xianhua Cai

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Abstract

Introduction: This study aimed to investigate the effects of stromal cell-derived factor-1 (SDF-1) and activation of its receptor, chemokine receptor 4 (CXCR4), on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and the key signaling mechanisms involved in these effects.

Material and methods: BMSCs were treated with 100 μg/L SDF-1 and cultured in osteogenic medium for 7 days. RT-qPCR and western blotting were used to detect the protein and mRNA levels of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), Runt-related transcription factor 2 (Runx2), and osteocalcin (OCN). Alizarin-red staining was used to detect the mineralization-inducing ability of the cells.

Results: After BMSCs were treated with SDF-1, the levels of JAK2 mRNA, STAT3 mRNA, and protein phosphorylation increased, the number of mineralized nodules of BMSCs increased, and the osteogenic-differentiation ability was enhanced. In addition, after BMSCs were treated with an inhibitor of JAK2 phosphorylation, the levels of JAK2, STAT3, Runx2, and OCN decreased significantly, the number of mineralized nodules of BMSCs also decreased, and the osteogenic-differentiation ability decreased. The inhibition of CXCR4-treated BMSCs further confirmed that SDF-1/CXCR4 activated JAK2/STAT3 to regulate the osteogenic differentiation of BMSCs.

Conclusions: SDF-1/CXCR4 promoted the osteogenic differentiation of BMSCs through JAK2/STAT3 activation.

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SDF-1/CXCR4轴通过JAK2/STAT3通路促进BMSCs成骨分化。

本研究旨在探讨基质细胞衍生因子-1 (SDF-1)及其受体趋化因子受体4 (CXCR4)的激活对骨髓间充质干细胞(BMSCs)成骨分化的影响，以及参与这些影响的关键信号机制。材料与方法:用100 μg/L SDF-1处理骨髓间充质干细胞，在成骨培养基中培养7 d。采用RT-qPCR和western blotting检测Janus kinase 2 (JAK2)、信号转导和转录激活因子3 (STAT3)、runt相关转录因子2 (Runx2)和骨钙素(OCN)的蛋白和mRNA水平。采用茜素红染色检测细胞的矿化诱导能力。结果:经SDF-1处理后，骨髓间充质干细胞JAK2 mRNA、STAT3 mRNA水平及蛋白磷酸化水平升高，矿化结节数量增加，成骨分化能力增强。此外，用JAK2磷酸化抑制剂处理骨髓间充质干细胞后，JAK2、STAT3、Runx2、OCN水平显著降低，骨髓间充质干细胞矿化结节数量减少，成骨分化能力下降。抑制CXCR4处理的骨髓间充质干细胞进一步证实了SDF-1/CXCR4激活JAK2/STAT3调控骨髓间充质干细胞成骨分化。结论:SDF-1/CXCR4通过激活JAK2/STAT3促进BMSCs成骨分化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.

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