MicroRNA-155 suppressed cholesterol-induced matrix degradation, pyroptosis and apoptosis by targeting RORα in nucleus pulposus cells.

Abstract

Intervertebral disc degeneration (IDD) is associated with low back pain, yet its inherent mechanism remains obscure. Hypercholesteremia was regarded as a risk factor for IDD, and our previous study showed that cholesterol accumulation could elicit matrix degradation in the nucleus pulposus (NP). MicroRNA-155 (miR-155) was substantiated as protective in IDD, but its role in cholesterol-induced IDD was unclear. The present study investigated whether miR-155 could mediate cholesterol-related IDD and its internal mechanisms. In vivo experiments revealed high-fat diet-induced hypercholesteremia in wild-type (WT) mice along with the occurrence of IDD, whereas Rm155LG transgenic mice showed milder NP degeneration, as evidenced by Saffron O-fast green (SF) staining and immunohistochemistry (IHC). Meanwhile, IHC showed that NLRP3 and Bax expression was also suppressed in Rm155LG mice. In vitro studies using Western blotting (WB) and immunofluorescence (IF) confirmed that the miR-155 mimic could alleviate cholesterol-induced matrix degradation, apoptosis and pyroptosis in NP. Moreover, RORα was upregulated in severely degenerated NP compared to mild IDD. It was also noted that RORα was suppressed in Rm155LG mice. In this study, we demonstrated that miR-155 could target RORα and that inhibition of RORα could prevent cholesterol-induced matrix degradation, apoptosis, and pyroptosis in NP, indicating the protective effect of miR-155 in cholesterol-induced IDD by targeting RORα.

• Authors: Tianyu Qin, Jiansen Yan, Shuangxing Li, Xiaolin Lin, Jiajun Wu, Zhengqi Huang, Chao Zhang, Yangyang Zhang, Zhihuai Deng, Dong Xiao, Song Jin, Yin Xiao, Kang Xu, Wei Ye
• Journal: Cellular signalling (Cell Signal) Vol. 107 Pg. 110678 (07 2023) ISSN: 1873-3913 [Electronic] England
• PMID: 37062437 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023. Published by Elsevier Inc.

Chemical References

• MicroRNAs
• Mirn155 microRNA, mouse
• Rora protein, mouse

Topics

• Animals
• Mice
• Apoptosis
• Hypercholesterolemia (metabolism)
• Intervertebral Disc Degeneration (genetics, metabolism)
• Mice, Transgenic
• MicroRNAs (genetics, metabolism)
• Nucleus Pulposus (metabolism)
• Pyroptosis