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Inhibition of microRNA-384-5p alleviates osteoarthritis through its effects on inhibiting apoptosis of cartilage cells via the NF-κB signaling pathway by targeting SOX9

Cancer Gene Therapy volume 25, pages 326–338 (2018)Cite this article

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A Correction to this article was published on 29 July 2020

This article has been updated

Abstract

Osteoarthritis (OA), a major cause of pain and disability, is a serious public issue worldwide. Some microRNAs (miRNAs) and SOX9 have been found to be expressed in OA. Therefore, the aim of this study is to investigate effects of microRNA-384-5p (miR-384-5p) on cartilage cell proliferation and apoptosis in mice with OA by targeting SOX9 through the NF-κB signaling pathway. First, bioinformatics was used to predict the SOX9-mediated miRNA (miR-384-5p), and dual luciferase reporter gene assay was conducted to further verify the relationship between miR-384-5p and SOX9. Then, the expression of miR-384-5p, SOX9, and NF-kB in mice modeled with OA was detected. To investigate the specific mechanism of miR-384-5p in OA, mimic and inhibitor of miR-384-5p and siRNA against SOX9 were used to transfect cartilage cells. Finally, proliferation, cell cycle, and cell apoptosis were detected using MTT assay and flow cytometry, respectively. Our results indicated that OA mice exhibited decreased expression of SOX9 and NF-kB but higher miR-384-5p expression. In addition, over-expressed miR-384-5p or silenced SOX9 could inhibit cell proliferation, and block cell cycle entry and induces apoptosis. SOX9 was a target gene of miR-384-5p. The NF-kB signaling pathway was inactivated after overexpression of miR-384-5p. Furthermore, we also observed that the effect of miR-384-5p inhibition was rescued when SOX9 was knocked down. The results support the view that inhibition of miR-384-5p could impede apoptosis and promote proliferation of cartilage cells through activating the NF-κB signaling pathway by promoting SOX9, thereby preventing the development of OA.

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Change history

  • 29 July 2020

    The original version of this Article contained inaccuracies in Figure 6B (“Sox9” band) and Figure 8A (“mir-384-5p inhibitor” and “8 mir-384-5p inhibitor + sirna-sox9” groups). Both figures have been corrected in the PDF and HTML versions of the Article.

  • 29 July 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgments

 This study was supported by Natural Science Foundation of Xinjiang Uygur Autonomous Regions Province of China (Project: 2014211C093).We would like to acknowledge the helpful comments on this paper received from our reviewers.

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  1. Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P.R. China

    Weikai Zhang, Peng Cheng, Weihua Hu, Weifeng Yin, Fengjing Guo, Anmin Chen & Hui Huang

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  1. Weikai Zhang
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Correspondence to Hui Huang.

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Zhang, W., Cheng, P., Hu, W. et al. Inhibition of microRNA-384-5p alleviates osteoarthritis through its effects on inhibiting apoptosis of cartilage cells via the NF-κB signaling pathway by targeting SOX9. Cancer Gene Ther 25, 326–338 (2018). https://doi.org/10.1038/s41417-018-0029-y

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