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

被引:22
作者
Cai, Zhongxu [1 ]
Li, Kunpeng [2 ]
Yang, Keshi [2 ]
Luo, Dawei [2 ]
Xu, Hui [2 ]
机构
[1] Dongying Peoples Hosp, Dept Spinal Surg, 317 Nanyi Rd, Dongying 257091, Shandong, Peoples R China
[2] Liaocheng Peoples Hosp, Dept Spinal Surg, 67 Dongchang Xilu Rd, Liaocheng 252000, Shandong, Peoples R China
关键词
BACK; CHONDROCYTES; DEGRADATION; AUTOPHAGY;
D O I
10.1038/s41434-019-0118-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:417 / 426
页数:10
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