Melatonin protects vertebral endplate chondrocytes against apoptosis and calcification via the Sirt1-autophagy pathway
Authors: Naifeng Tian
Xiangyang Wang
Weiyang Gao
Jialiang Lin
Tingting Chen
Zengjie Zhang
Chenggui Wang
Xiaolei Zhang
Qingqing Wang
Majid Nisar
Yifei Zhou
Yaosen Wu
Haiming Jin
Gang Zheng
Tianzhen Xu
Journal: Journal of Cellular and Molecular Medicine (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: apoptosis; autophagy; calcification; intervertebral disc degeneration; melatonin
Affiliations: Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China., Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, Zhejiang Province, China., The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China., The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China., The Third Affiliated Hospital and Ruian People's Hospital of Wenzhou Medical University, Ruian, Zhejiang Province, China., Chinese Orthopaedic Regenerative Medicine Society, Zhejiang University of School Medicne, HangZhou, China.

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. 

Retracted: No

PubPeer comments:
 After claiming the deficiencies of some existing ranking methods for intuitionistic fuzzy numbers and interval valued intuitionistic fuzzy numbers, the authors proposed a new one in Definition 1 and applied it to multi-attribute decision making. However, the pairs $(a, b)$ and $(c, d)$ in eq.(17) are not in a symmetric form. The authors did not address the order reversing issue with respect to the ranking using eq.(17). That is, the following question is not answered **Is it possible that $S(tilde{a}) S(tilde{b})$ and $S(tilde{a}^c) S(tilde{b}^c)$ occur simultaneously?** This issue is crucial to justify the proposed new ranking method before considering the order-preserving issues with respect to the u201cadditionu201d and u201cscalar multiplicationu201d operations. See also the comments for two similar papers on https: pubpeer.com publications B2233F4E085BE033E16F7495CB7D67 https: pubpeer.com publications 8E52FAAE41A4EB4D2658CADB0E2016 ![file] ,