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World J Stem Cells. Nov 26, 2025; 17(11): 112393
Published online Nov 26, 2025. doi: 10.4252/wjsc.v17.i11.112393
Thymoquinone inhibited the chondrogenic differentiation of tendon-derived stem cells caused by tendon injury
Yi-Jun Tu, Yun-Qi Liu, Yan-Yan Pan, Hong-Yang Cai, Chang Liu
Yi-Jun Tu, Yun-Qi Liu, Yan-Yan Pan, Hong-Yang Cai, Chang Liu, Central Hospital of Dalian University of Technology, Dalian 116033, Liaoning Province, China
Author contributions: Tu YJ performed the experiments and acquired the data; Tu YJ and Liu C interpreted the data; Liu YQ, Pan YY, and Cai HY helped perform the experiments; Liu C provided the conception, designed the research, drafted, and revised the manuscript. All authors have read and approved the final submitted manuscript.
Supported by the Department of Science & Technology of Liaoning Province, No. 2024-MS-285; and National Natural Science Foundation of China, No. 82303572.
Institutional animal care and use committee statement: The animal protocol was reviewed and agreed by the Ethic Committee of Central Hospital of Dalian University of Technology, in accordance with the general rules for the welfare of laboratory animals (No. GB_T42011-2022). The animal protocol was designed to minimize pain or discomfort to the animals. The animals were acclimatized to laboratory conditions (23 °C, 12 hours/12 hours light/dark, 50% humidity, ad libitum access to food and water), for 2 weeks prior to experimentation. All animals were euthanized by barbiturate overdose (intravenous injection, 150 mg/kg pentobarbital sodium) for tissue collection.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The datasets generated and/or analyzed during the current study are available in the figshare repository (https://10.6084/m9.figshare.29486207).
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chang Liu, PhD, Affiliate Associate Professor, Central Hospital of Dalian University of Technology, No. 826 Southwest Road, Dalian 116033, Liaoning Province, China. liuch2024@dlut.edu.cn
Received: July 31, 2025
Revised: August 18, 2025
Accepted: November 3, 2025
Published online: November 26, 2025
Processing time: 119 Days and 3.7 Hours
Core Tip

Core Tip: In our previous investigation, we demonstrated that micro-injured tendon with 6.4% strain promoted the chondrogenic differentiation of tendon-derived stem cells, by activating endoplasmic reticulum (ER) stress. To further validate this phenomenon in the animal model, we established a rat Achilles tendon injury model via treadmill running. In the present study, tendon injury was found to activate ER stress by upregulating the protein kinase RNA-like ER kinase/eukaryotic initiation factor 2/activating transcription factor 4/CCAAT/enhancer-binding protein homologous protein pathway. And thymoquinone was shown to alleviate ER stress, while inhibiting the chondrogenic differentiation of tendon-derived stem cells in both in vitro and in vivo models. These findings suggest that thymoquinone may hold potential as a preventive and therapeutic agent for tendinopathy.