Urolithin A-induced mitophagy suppresses apoptosis and attenuates intervertebral disc degeneration via the AMPK signaling pathway

  • Free Radic Biol Med. 2020 Apr:150:109-119. doi: 10.1016/j.freeradbiomed.2020.02.024.
Jialiang Lin  1 ,  Jinru Zhuge  2 ,  Xuanqi Zheng  1 ,  Yuhao Wu  3 ,  Zengjie Zhang  1 ,  Tianzhen Xu  1 ,  Zaher Meftah  1 ,  Hongming Xu  4 ,  Yaosen Wu  1 ,  Naifeng Tian  1 ,  Weiyang Gao  1 ,  Yifei Zhou  5 ,  Xiaolei Zhang  6 ,  Xiangyang Wang  7
Affiliations
  • 1. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 2. The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 3. The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 4. Department of Orthopaedic Surgery, Affiliated Cixi Hospital of Wenzhou Medical University, Ningbo, Zhejiang Province, China.
  • 5. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: [email protected].
  • 6. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Chinese Orthopaedic Regenerative Medicine Society, Hangzhou, Zhejiang Province, China. Electronic address: [email protected].
  • 7. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: [email protected].
PMID: 32105828 DOI: 10.1016/j.freeradbiomed.2020.02.024
Abstract

Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and effective therapies are still lacking. Previous studies reported that mitochondrial dysfunction contributes to Apoptosis, and urolithin A (UA) specifically induces Mitophagy. Herein, we aimed to investigate the protective effect of UA-induced Mitophagy on tert-butyl hydroperoxide (TBHP)-induced Apoptosis in nucleus pulposus (NP) cells in vitro and a rat model of IDD in vivo. Mitochondrial function, Apoptosis, and Mitophagy were measured in UA-treated NP cells by western blotting and immunofluorescence; the therapeutic effects of UA on IDD were assessed in rats with puncture-induced IDD. The results showed that UA could activate Mitophagy in primary NP cells, and UA treatment inhibited TBHP-induced mitochondrial dysfunction and the intrinsic Apoptosis pathway. Mechanistically, we revealed that UA promoted Mitophagy by activating AMPK signaling in TBHP-induced NP cells. In vivo, UA was shown to effectively alleviate the progression of puncture-induced IDD in rats. Taken together, our results suggest that UA could be a novel and effective therapeutic strategy for IDD.

Keywords
AMPK; Apoptosis; Intervertebral disc degeneration; Mitophagy; Urolithin A.
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