Icariin Alleviates IL-1β-Induced Matrix Degradation By Activating The Nrf2/ARE Pathway In Human Chondrocytes
Authors Zuo S, Zou W, Wu RM, Yang J, Fan JN, Zhao XK, Li HY
Received 27 January 2019
Accepted for publication 29 October 2019
Published 21 November 2019 Volume 2019:13 Pages 3949—3961
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 3
Editor who approved publication: Professor Manfred Ogris
Shi Zuo,1,* Wei Zou,2,3,* Rong-Min Wu,4 Jing Yang,5 Jian-Nan Fan,2 Xue-Ke Zhao,5 Hai-Yang Li1
1Department of Hepatobiliary Surgery, The Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Sports Medicine, The Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Department of Orthopedics, The Fourth People’s Hospital of Guiyang, Guizhou, People’s Republic of China; 4Department of Ultrasonography, The Maternity Hospital of Guizhou, Guiyang, Guizhou, People’s Republic of China; 5Department of Infectious Disease, The Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Hai-Yang Li
Department of Hepatobiliary Surgery, The Hospital Affiliated to Guizhou Medical University, No.28, Guiyi Street, Guiyang, Guizhou 550004, People’s Republic of China
Department of Sports Medicine, The Hospital Affiliated to Guizhou Medical University, No.28, Guiyi Street, Guiyang, Guizhou 550004, People’s Republic of China
Objective: Osteoarthritis (OA) is characterized by progressive matrix destruction of articular cartilage. This study aimed to investigate the potential antioxidative and chondroprotective effects and underlying mechanism of Icariin (ICA) in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage.
Methods: Human chondrocyte cell line HC-A was treated with different doses of ICA, and then MTT assay and PI staining were used to estimate ICA-induced chondrocyte apoptosis. Intracellular ROS and superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured after treatment by IL-1β with or without ICA. The mRNA and protein expression levels of redox transcription factor Nrf2 and the downstream effector SOD-1, SOD-2, NQO-1 and HO-1 were assayed to explore the detailed mechanism by which ICA alleviates ECM degradation. Finally, to expound the role of Nrf2 in ICA-mediated chondroprotection, we specifically depleted Nrf2 in human chondrocytes and then pretreated them with ICA followed by IL-1β.
Results: ICA had no cytotoxic effects on human chondrocytes and 10−9 M was selected as the optimum concentration. ROS induced by IL-1β could drastically activate matrix-degrading proteases and ICA could significantly rescue the matrix degradation and excess ROS generation caused by IL-1β. We observed that ICA activated the Nrf2/ARE pathway, consequently upregulating the generation of GPX and SOD. Ablation of Nrf2 abrogated the chondroprotective and antioxidative effects of ICA in IL-1β-treated chondrocytes.
Conclusion: ICA alleviates IL-1β-induced matrix degradation and eliminates ROS by activating the Nrf2/ARE pathway.
Keywords: icariin, Nrf2 signaling, ROS, human chondrocyte, ECM degradation
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