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Down-Regulation of microRNA-30d Alleviates Intervertebral Disc Degeneration Through the Promotion of FOXO3 and Suppression of CXCL10

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A Correction to this article was published on 04 February 2022

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Abstract

MicroRNAs (miRNAs/miRs) are important biomarkers for the progression of intervertebral disc degeneration (IDD). We investigated the role of miR-30d in IDD progression through its interactions with forkhead box O3 (FOXO3) and C-X-C motif ligand 10 (CXCL10). We first measured the expression of miR-30d, FOXO3, and CXCL10 in NP cells cultured from IDD patients. RNA-immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were then employed to test the relationship among miR-30d, FOXO3, and CXCL10. Besides, gain- and loss-of function approaches were performed to assess the functional roles of miR-30d and FOXO3 in IDD in vitro and in vivo. We found high expression of miR-30d and CXCL10 and low expression of FOXO3 in IDD. We showed that miR-30d specifically targeted FOXO3, and that down-regulation of miR-30d promoted proliferation and inhibited apoptosis of NP cells in IDD by increasing the expression of FOXO3. Besides, FOXO3 inhibited apoptosis of NP cells by downregulation of CXCL10 expression. Moreover, inhibition of miR-30d promoted proliferation and inhibited apoptosis of NP cells in IDD by decreasing CXCL10. Furthermore, findings in the mouse IDD model confirmed the inhibitory role of decreased miR-30d in IDD progression. Thus, we show that downregulation of miR-30d could promote the proliferation of NP cells by increasing FOXO3 and decreasing CXCL10 expression, which may provide a novel therapeutic target for IDD.

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Authors and Affiliations

  1. Department of Orthopedics, Second Hospital of Jilin University, Changchun, 132000, People’s Republic of China

    Peng Xia & Yifu Sun

  2. Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, 130033, Jilin Province, People’s Republic of China

    Xu Gao, Fang Li & Liwei Shao

Authors
  1. Peng Xia
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  2. Xu Gao
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  3. Fang Li
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  5. Yifu Sun
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Contributions

PX, XG, FL, LWS and YFS designed the study. PX collated the data, carried out data analyses and produced the initial draft of the manuscript. XG, FL, LWS and YFS contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.

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Correspondence to Yifu Sun.

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The authors declare that they have no conflict of interest.

Research Involving Human and Animal Rights

Study protocols were approved by Ethic Committee of China-Japan Union Hospital of Jilin University and followed the ethical principles for medical research involving human subjects of the Declaration of Helsinki. The animal experiments were performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and followed a protocol approved by the Institutional Animal Care and Use Committee of China-Japan Union Hospital of Jilin University. All efforts were made to minimize the discomfort of the included animals.

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Written informed consent was obtained from all patients prior to the study.

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Xia, P., Gao, X., Li, F. et al. Down-Regulation of microRNA-30d Alleviates Intervertebral Disc Degeneration Through the Promotion of FOXO3 and Suppression of CXCL10. Calcif Tissue Int 108, 252–264 (2021). https://doi.org/10.1007/s00223-020-00760-w

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  • DOI: https://doi.org/10.1007/s00223-020-00760-w

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