International Journal of Biological Sciences

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Int J Biol Sci 2018; 14(6):682-692. doi:10.7150/ijbs.24081

Research Paper

Berberine suppresses apoptosis and extracellular matrix (ECM) degradation in nucleus pulposus cells and ameliorates disc degeneration in a rodent model

Yu Chen1,2#, Zengming Zheng1,2#, Jianle Wang1, Chengxuan Tang1, Sinan Khor3, Jian Chen1, Xibang Chen1, Zengjie Zhang1, Qian Tang1, Chenggui Wang1, Yiting Lou1, Zhouguang Wang2✉, Jian Xiao1✉, Xiangyang Wang1✉

1. Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 325027 Wenzhou, China
2. Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, 325035, Wenzhou, China
3. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, U.S.A.
4. Department of Orthopaedic Surgery, Ruian Peoples Hospital & the 3rd Hospital Affiliated to Wenzhou Medical University, 325200 Ruian, China
# These authors contributed equally to this work.

Abstract

Intervertebral disc degeneration (IVDD) is a chronic disease with complicated pathology involving nucleus pulposus (NP) cell apoptosis and extracellular matrix (ECM) degradation. Previous studies have shown that moderate autophagy has a protective effect against apoptosis in NP cells. Berberine (BBR) is an alkaloid compound with many beneficial properties including antimicrobial, anti-inflammatory, antioxidative, and anti-apoptotic activity. Recently, it was found to induce autophagy in various tissues as well. Thus, we hypothesized that BBR may exert a therapeutic effect on IVDD through autophagy activation. In this study, we investigated the effects of BBR on IVDD and delineated a potential mechanism. BBR treatment in vitro inhibited the expression of pro-apoptotic proteins induced by tert-butyl hydroperoxide (TBHP), and increased the expression of anti-apoptotic Bcl-2. Furthermore, it prevented ECM degradation by inhibiting the production of matrix-degrading enzymes. Additionally, BBR treatment significantly activated autophagy in NP cells. However, autophagy inhibition markedly suppressed BBR's effects on NP cell apoptosis and ECM degeneration, indicating that autophagy activation with BBR treatment is protective against IVDD. In vivo, BBR treatment increased the expression of LC3 in disc cells and prevented the development of IVDD in a needle puncture-induced rat model. Thus, BBR stimulates autophagy as a protective mechanism against NP cell apoptosis and ECM degeneration, revealing its therapeutic potential in the treatment of IVDD.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Chen Y, Zheng Z, Wang J, Tang C, Khor S, Chen J, Chen X, Zhang Z, Tang Q, Wang C, Lou Y, Wang Z, Xiao J, Wang X. Berberine suppresses apoptosis and extracellular matrix (ECM) degradation in nucleus pulposus cells and ameliorates disc degeneration in a rodent model. Int J Biol Sci 2018; 14(6):682-692. doi:10.7150/ijbs.24081. Available from http://www.ijbs.com/v14p0682.htm