Research Paper Volume 12, Issue 19 pp 19254—19272
S-allyl cysteine reduces osteoarthritis pathology in the tert-butyl hydroperoxide-treated chondrocytes and the destabilization of the medial meniscus model mice via the Nrf2 signaling pathway
- 1 Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
- 2 Key Laboratory of Orthopedics of Zhejiang Province, Wenzhou, Zhejiang Province, China
- 3 The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
- 4 Department of Orthopedics, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
- 5 Chinese Orthopedic Regenerative Medicine Society, Hangzhou, Zhejiang Province, China
Received: February 28, 2020 Accepted: June 19, 2020 Published: October 7, 2020
https://doi.org/10.18632/aging.103757How to Cite
Copyright: © 2020 Shao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
In this study, we used murine chondrocytes as an in vitro model and mice exhibiting destabilization of the medial meniscus (DMM) as an in vivo model to investigate the mechanisms through which S-allyl cysteine (SAC) alleviates osteoarthritis (OA). SAC significantly reduced apoptosis and senescence and maintained homeostasis of extracellular matrix (ECM) metabolism in tert-butyl hydroperoxide (TBHP)-treated chondrocytes. Molecular docking analysis showed a –CDOCKER interaction energy value of 203.76 kcal/mol for interactions between SAC and nuclear factor erythroid 2-related factor 2 (Nrf2). SAC increased the nuclear translocation of Nrf2 and activated the Nrf2/HO1 signaling pathway in TBHP-treated chondrocytes. Furthermore, Nrf2 knockdown abrogated the antiapoptotic, antisenescence, and ECM regulatory effects of SAC in TBHP-treated chondrocytes. SAC treatment also significantly reduced cartilage ossification and erosion, joint-space narrowing, synovial thickening and hypercellularity in DMM model mice. Collectively, these findings show that SAC ameliorates OA pathology in TBHP-treated chondrocytes and DMM model mice by activating the Nrf2/HO1 signaling pathway.