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

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

  • Cell Signal. 2023 Apr 14;107:110678. doi: 10.1016/j.cellsig.2023.110678.
Tianyu Qin 1,  Jiansen Yan 2,  Shuangxing Li 3,  Xiaolin Lin 4,  Jiajun Wu 2,  Zhengqi Huang 2,  Chao Zhang 2,  Yangyang Zhang 2,  Zhihuai Deng 2,  Dong Xiao 5,  Song Jin 6,  Yin Xiao 7,  Kang Xu 8,  Wei Ye 9
Affiliations

Affiliations

  • 1 Department of Orthopedics, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 528406, China; Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
  • 2 Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
  • 3 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Department of Orthopedics, Sun Yat-sen Memorial Hospital Shenshan Central Hospital of Sun Yat-sen University, Shanwei 516621, China.
  • 4 Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China; Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China.
  • 5 Institute of Comparative Medicine & Laboratory Animal Center, Southern Medical University, Guangzhou 510515, China.
  • 6 Department of Orthopedics, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen 528406, China.
  • 7 School of Medicine and Dentistry & Menzies Health Institute Queensland, Griffith University, QLD 4222, Australia; Australia-China Centre for Tissue Engineering and Regenerative Medicine, Griffith University and Queensland University of Technology, Brisbane, QLD 4222, Australia.
  • 8 Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Electronic address: [email protected].
  • 9 Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Electronic address: [email protected].
PMID: 37062437 DOI: 10.1016/j.cellsig.2023.110678
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.

Keywords

Apoptosis; Cholesterol; Intervertebral disc degeneration; MicroRNA-155; Pyroptosis; RORα.

Figures
Products