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Suppression of miR-203-3p inhibits lipopolysaccharide induced human intervertebral disc inflammation and degeneration through upregulating estrogen receptor α

Gene Therapy volume 27, pages 417–426 (2020)Cite this article

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Abstract

Accumulating evidence demonstrates that estrogen receptor α (ERα) and microRNAs (miRNAs) play crucial roles in intervertebral disc degeneration (IDD). However, the specific miRNA that related with ERα during IDD development remains unknown. Therefore, we aimed to explore the role of ERα-related miRNA in the IDD model. Nucleus pulposus (NP) cells were isolated from IDD patients. ERα-related miRNAs were selected and verified in NP tissues from IDD patients using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Also, the related cytokine mRNA levels were detected by qRT-PCR. Protein levels were determined by Western blot. The concentrations of inflammatory cytokines in culture supernatants were detected by enzyme-linked immunosorbent assay. MiR-203-3p was found to be upregulated in NP tissues of high-grade IDD patients compared with low-grade IDD patients, and negatively associated with ERα expression. MiR-203-3p directly targeted ERα in NP cells of IDD patients. After lipopolysaccharides (LPS) stimulation, miR-203-3p expression increased, while ERα expression decreased in NP cells. MiR-203-3p inhibition suppressed the effect of LPS on ERα expression and IDD related genes, while ERα downregulation rescued the effect of LPS. In conclusion, suppression the expression of miR-203-3p could inhibit LPS-induced human intervertebral disc inflammation and degeneration through upregulating ERα.

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Funding

The study was supported by the Natural Science Foundation of Shandong Province (ZR2017MH112 and ZR2014HL027); A Shandong Province Medical Science and Technology Development Project (2016WS0206 and 2014WS0303).

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Author notes

  1. These authors contributed equally: Zhongxu Cai, Kunpeng Li

Authors and Affiliations

  1. Department of Spinal Surgery, Dongying People’s Hospital, No. 317, Nanyi Road, Dongying, 257091, Shandong, China

    Zhongxu Cai

  2. Department of Spinal Surgery, Liaocheng People’s Hospital, No. 67, Dongchang Xilu Road, Liaocheng, 252000, Shandong, China

    Kunpeng Li, Keshi Yang, Dawei Luo & Hui Xu

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  1. Zhongxu Cai
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  2. Kunpeng Li
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Correspondence to Hui Xu.

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Cai, Z., Li, K., Yang, K. et al. Suppression of miR-203-3p inhibits lipopolysaccharide induced human intervertebral disc inflammation and degeneration through upregulating estrogen receptor α. Gene Ther 27, 417–426 (2020). https://doi.org/10.1038/s41434-019-0118-z

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