2. Academic Validation
  3. Urolithin A-induced mitophagy suppresses apoptosis and attenuates intervertebral disc degeneration via the AMPK signaling pathway

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

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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