Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1-autophagy pathway.

Zengjie Zhang, Jialiang Lin, Naifeng Tian, Yaosen Wu, Yifei Zhou, Chenggui Wang, Qingqing Wang, Haiming Jin, Tingting Chen, Majid Nisar, Gang Zheng, Tianzhen Xu, Weiyang Gao, Xiaolei Zhang, Xiangyang Wang
Author Information
  1. Zengjie Zhang: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  2. Jialiang Lin: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  3. Naifeng Tian: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  4. Yaosen Wu: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  5. Yifei Zhou: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  6. Chenggui Wang: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  7. Qingqing Wang: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  8. Haiming Jin: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  9. Tingting Chen: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  10. Majid Nisar: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  11. Gang Zheng: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  12. Tianzhen Xu: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  13. Weiyang Gao: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  14. Xiaolei Zhang: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. ORCID
  15. Xiangyang Wang: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China. ORCID

Abstract

Melatonin is reportedly associated with intervertebral disc degeneration (IDD). Endplate cartilage is vitally important to intervertebral discs in physiological and pathological conditions. However, the effects and mechanism of melatonin on endplate chondrocytes (EPCs) are still unclear. Herein, we studied the effects of melatonin on EPC apoptosis and calcification and elucidated the underlying mechanism. Our study revealed that melatonin treatment decreases the incidence of apoptosis and inhibits EPC calcification in a dose-dependent manner. We also found that melatonin upregulates Sirt1 expression and activity and promotes autophagy in EPCs. Autophagy inhibition by 3-methyladenine reversed the protective effect of melatonin on apoptosis and calcification, while the Sirt1 inhibitor EX-527 suppressed melatonin-induced autophagy and the protective effects of melatonin against apoptosis and calcification, indicating that the beneficial effects of melatonin in EPCs are mediated through the Sirt1-autophagy pathway. Furthermore, melatonin may ameliorate IDD in vivo in rats. Collectively, this study revealed that melatonin reduces EPC apoptosis and calcification and that the underlying mechanism may be related to Sirt1-autophagy pathway regulation, which may help us better understand the association between melatonin and IDD.

Keywords

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MeSH Term

Animals
Apoptosis
Autophagy
Calcinosis
Carbazoles
Cells, Cultured
Chondrocytes
Disease Models, Animal
Female
Intervertebral Disc Degeneration
Male
Melatonin
Oxidative Stress
Protective Agents
Rats, Sprague-Dawley
Sirtuin 1
tert-Butylhydroperoxide

Chemicals

6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide
Carbazoles
Protective Agents
tert-Butylhydroperoxide
Sirt1 protein, rat
Sirtuin 1
Melatonin

Word Cloud

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