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Copyright (c) 2023 Chunye Tan, Linwei Li, Wenming Ma, Jinlong Zhang, Weiqi Ling
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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.GSDMD inhibitor protects chondrocyte from mechanical injury in human articular cartilage
Corresponding Author(s) : Weiqi Ling
Cellular and Molecular Biology,
Vol. 69 No. 10: Issue 10
Abstract
Traumatic arthritis is caused by mechanical injury and results in the degeneration of articular cartilage, but it is unclear whether it is related to the pyroptosis of chondrocyte (CHs). Thus, this study was designed to investigate the role of GSDMD, the executor of pyroptosis, in the human cartilage during mechanical injury. We collected the human hip joint and used a loading apparatus to produce compression on the cartilage disc. After one hour of 15 MPa or 25 MPa injury, the acute and chronic effects of the mechanical injury on the cartilage were tested. We stained the CHs in the cartilage with calcein and DAPI to calculate the live-cell rate. The chondrogenic phenotype was determined by analyzing the mRNA levels of type II collagen alpha 1 (Col2A1), type I collagen alpha 2 (Col2A1), and SOX9. Besides, the pyroptosis process was determined by the mRNA levels of caspase-1/5, GSDMD, IL-1β, and IL-18. We also explored the preventive role and therapeutic role of GSDMD inhibitors in mechanical injury via culturing the cartilage before and after the compression, respectively. Mechanical compression injured the viability and function of CHs in cartilage partly based on the pyroptosis. The pretreatment of GSDMD inhibitor in cartilage before injury could maintain the live cells and Col2A1 expression and prevent pyroptosis after injury. Besides, supplying the cartilage with GSDMD inhibitor after injury also alleviated the cell death and dysfunction of CHs, and suppressed the pyroptosis. Using an inhibitor of GSDMD can play a preventive role and play a therapeutic role in the mechanical injury of cartilage.
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