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

作者：Qin, Tianyu; Yan, Jiansen; Li, Shuangxing; Lin, Xiaolin; Wu, Jiajun; Huang, Zhengqi; Zhang, Chao; Zhang, Yangyang; Deng, Zhihuai; Xiao, Dong; Jin, Song; Xiao, Yin; Xu, Kang^*; Ye, Wei^*

来源：Cellular Signalling, 2023, 107: 110678.

DOI：10.1016/j.cellsig.2023.110678

• Cholesterol
• MicroRNA-155
• ROR alpha
• Pyroptosis
• Apoptosis
• Intervertebral disc degeneration

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 ex-periments 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, RORa was upregulated in severely degenerated NP compared to mild IDD. It was also noted that RORa was suppressed in Rm155LG mice. In this study, we demonstrated that miR-155 could target RORa and that inhibition of RORa could prevent cholesterol-induced matrix degradation, apoptosis, and pyroptosis in NP, indicating the protective effect of miR-155 in cholesterol-induced IDD by targeting RORa.

• 单位
  中山大学; 南方医科大学