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

Accumulating evidence demonstrates that estrogen receptor [alpha] (ER[alpha]) and microRNAs (miRNAs) play crucial roles in intervertebral disc degeneration (IDD). However, the specific miRNA that related with ER[alpha] during IDD development remains unknown. Therefore, we aimed to explore the role o...

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Published inGene therapy Vol. 27; no. 9; pp. 417 - 426
Main Authors Cai, Zhongxu, Li, Kunpeng, Yang, Keshi, Luo, Dawei, Xu, Hui
Format Journal Article
LanguageEnglish
Published Nature Publishing Group 01.09.2020
Subjects
Cytokines
Enzyme-linked immunosorbent assay
Estrogen
Inflammation
MicroRNA
Mitogens
Phenols
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Summary:Accumulating evidence demonstrates that estrogen receptor [alpha] (ER[alpha]) and microRNAs (miRNAs) play crucial roles in intervertebral disc degeneration (IDD). However, the specific miRNA that related with ER[alpha] during IDD development remains unknown. Therefore, we aimed to explore the role of ER[alpha]-related miRNA in the IDD model. Nucleus pulposus (NP) cells were isolated from IDD patients. ER[alpha]-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 ER[alpha] expression. MiR-203-3p directly targeted ER[alpha] in NP cells of IDD patients. After lipopolysaccharides (LPS) stimulation, miR-203-3p expression increased, while ER[alpha] expression decreased in NP cells. MiR-203-3p inhibition suppressed the effect of LPS on ER[alpha] expression and IDD related genes, while ER[alpha] 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 ER[alpha].
ISSN:0969-7128
1476-5462
DOI:10.1038/s41434-019-0118-z