Zhang JW. Letter to the Editor: Thymoquinone targets endoplasmic reticulum stress to rescue tendon stem cell identity - a new era for tendinopathy therapy. World J Stem Cells 2026; 18(6): 116276 [DOI: 10.4252/wjsc.116276]
Corresponding Author of This Article
Jin-Wei Zhang, Institute of Biomedical and Clinical Sciences, Medical School, Faculty of Health and Life Sciences, University of Exeter, Hatherly Laboratories, Streatham Campus, Stocker Road, Exeter EX4 4PS, United Kingdom. j.zhang5@exeter.ac.uk
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Biology
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letter
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Zhang JW. Letter to the Editor: Thymoquinone targets endoplasmic reticulum stress to rescue tendon stem cell identity - a new era for tendinopathy therapy. World J Stem Cells 2026; 18(6): 116276 [DOI: 10.4252/wjsc.116276]
World J Stem Cells. Jun 26, 2026; 18(6): 116276 Published online Jun 26, 2026. doi: 10.4252/wjsc.116276
Letter to the Editor: Thymoquinone targets endoplasmic reticulum stress to rescue tendon stem cell identity - a new era for tendinopathy therapy
Jin-Wei Zhang
Jin-Wei Zhang, Institute of Biomedical and Clinical Sciences, Medical School, Faculty of Health and Life Sciences, University of Exeter, Hatherly Laboratories, Streatham Campus, Exeter EX4 4PS, United Kingdom
Jin-Wei Zhang, State Key Laboratory of Chemical Biology, Research Center of Chemical Kinomics, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
Author contributions: Zhang JW designed the overall concept and outline of the manuscript; Zhang JW contributed to the discussion and design of the manuscript, the writing and editing of the manuscript, illustrations, and review of the literature.
Supported by the National Natural Science Foundation of China, No. 82170406 and No. 81970238; and the Royal Society United Kingdom, No. IEC\NSFC\201094.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Corresponding author: Jin-Wei Zhang, Institute of Biomedical and Clinical Sciences, Medical School, Faculty of Health and Life Sciences, University of Exeter, Hatherly Laboratories, Streatham Campus, Stocker Road, Exeter EX4 4PS, United Kingdom. j.zhang5@exeter.ac.uk
Received: November 7, 2025 Revised: November 30, 2025 Accepted: January 12, 2026 Published online: June 26, 2026 Processing time: 230 Days and 23.3 Hours
Abstract
Tendinopathy is a chronic and degenerative tendon disorder with limited therapeutic options. Recent insights into the cellular pathogenesis of tendinopathy have revealed that tendon-derived stem cells may aberrantly differentiate into chondrocytes under micro-injury-induced endoplasmic reticulum stress. In a recent study published by Tu et al in the World Journal of Stem Cells, thymoquinone - a bioactive compound from Nigella sativa - was demonstrated to inhibit the chondrogenic differentiation of tendon-derived stem cells both in vitro and in vivo, primarily through attenuation of the protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2/activating transcription factor 4/CCAAT/enhancer-binding protein homologous protein pathway. This article evaluates the significance of these findings within the broader field of tendon biology, highlights methodological strengths, and discusses future research directions for translating thymoquinone into a potential therapy for tendinopathy.
Core Tip: This article critically analyzes the study by Tu et al, which demonstrated that tendon micro-injury activates endoplasmic reticulum (ER) stress signaling through the protein kinase RNA-like ER kinase/eukaryotic initiation factor 2/activating transcription factor 4/enhancer-binding protein homologous protein pathway, thereby promoting the chondrogenic differentiation of tendon-derived stem cells. Treatment with thymoquinone markedly alleviated ER stress and suppressed aberrant differentiation both in cultured cells and an in vivo rat model of treadmill-induced tendon injury. Collectively, these findings highlight thymoquinone as a promising therapeutic candidate for the prevention and treatment of tendinopathy by targeting ER stress-mediated cellular misdifferentiation.
