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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Urolithin a alleviates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells through SIRT1/PGC-1α pathway
Peng-Zhi Shi, Jun-Wu Wang, Ping-Chuan Wang, Bo Han, Xu-Hua Lu, Yong-Xin Ren, Xin-Min Feng, Xiao-Fei Cheng, Liang Zhang
Peng-Zhi Shi, Department of Orthopedic, Dalian Medical University, Dalian 116000, Liaoning Province, China
Jun-Wu Wang, Ping-Chuan Wang, Xin-Min Feng, Liang Zhang, Department of Orthopedics, Clinical Medical College of Yangzhou University, Yangzhou 225000, Jiangsu Province, China
Bo Han, Department of Orthopedic, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
Xu-Hua Lu, Department of Orthopedics, Changzheng Hospital of The Second Military Medical University, Shanghai 200003, China
Yong-Xin Ren, Department of Orthopedics, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Xiao-Fei Cheng, Department of Orthopedic Surgery, Shanghai Key Laboratory of Orthopedics Implants, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011, China
Author contributions: Shi PZ and Wang JW contributed to data curation, Writing- Original draft preparation, contributed equally to this work; Wang PC contributed to Visualization, Validation; Han B performed Investigation; Lu XH, Ren YX and Feng XM performed conceptualization, methodology; Cheng XF and Zhang L performed supervision, writing- reviewing, editing and share corresponding author.
Supported by National Natural Science Foundation of China, No. 81972136; Young Medical Scholars Major Program of Jiangsu Province, No. QNRC2016342; Key Funding Project of Maternal and Child Health Research of Jiangsu Province, No. F201801; and High-level Health Professionals "Six projects" Top-notch Talent Research Program of Jiangsu Province, No. LGY2019035.
Institutional review board statement: This study was approved by the Ethical Committee of the Clinical Medical College of Yangzhou University (SBYY2020-023).
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (Shanghai Institute of Family Planning Science, License No. SCXK (Hu) 2018-0006).
Conflict-of-interest statement: The authors have no relevant financial or non-financial interests to disclose.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Liang Zhang, Doctor, PhD, Chief Doctor, Professor, Surgeon, Department of Orthopedics, Clinical Medical College of Yangzhou University, No. 98 Nantong west Road, Yangzhou 225000, Jiangsu Province, China. zhangliang6320@sina.com
Received: July 2, 2021
Peer-review started: July 2, 2021
First decision: July 29, 2021
Revised: August 12, 2021
Accepted: November 28, 2021
Article in press: November 28, 2021
Published online: December 26, 2021
ARTICLE HIGHLIGHTS
Research background
Intervertebral disc degeneration (IDD) is the main pathogenic factor of low back pain, but its pathological mechanism has not yet been elucidated. The isolation and identification of nucleus pulposus-derived mesenchymal stem cells (NPMSCs) provided a basis for the endogenous repair of IDD.
Research motivation
An unfavorable microenvironment of degenerative intervertebral disc such as inflammation, oxidative stress, and increased catabolism leads to increased senescence NPMSCs, which seriously affects endogenous repair. Therefore, rescuing the activity of NPMSCs and delaying cell senescence is of great significance to alleviate IDD.
Research objectives
The present study investigated whether urolithin A (UA) could alleviate NPMSCs senescence induced by oxidative stress and the potential mechanism.
Research methods
The protective effects of UA against oxidative stress-induced senescence in NPMSCs were investigated by evaluating the senescence-associated β-Galactosidase (SA-β-Gal) activity, cell cycle, cell proliferation ability, mitochondrial function and reactive oxygen species (ROS). Additionally, the expression of senescence-related and the silent information regulator of transcription 1/PPAR gamma coactivator-1α (SIRT1/PGC-1α) pathway-related proteins and mRNA was also used to evaluate the protective effects of UA in vitro. In vivo, an animal model of IDD were constructed, and X-rays, magnetic resonance imaging, and histological analysis were used to assessed whether UA could alleviate IDD in vivo.
Research results
in vitro, UA could reduce SA-β-Gal activity and senescence-related proteins and mRNA (P16 and P21) expression, alleviate cell cycle arrest and ROS production, stimulate cell proliferation ability and mitochondrial function by activating the SIRT1/PGC-1α pathway. In vivo, UA could alleviate an animal model of IDD by assessed the disc height index, Pfirrmann grade and the histological score.
Research conclusions
UA could activate the SIRT1/PGC-1α signaling pathway to protect mitochondrial function and alleviate cell senescence, and further delay extracellular matrix degradation and IDD, which provide the possibility of promoting endogenous repair and retarding IDD.
Research perspectives
We demonstrated the positive role of UA in attenuating oxidative stress-induced NPMSCs senescence and delaying IDD. UA may be successfully applied to IDD endogenous repair.
