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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2025; 17(10): 109369
Published online Oct 26, 2025. doi: 10.4252/wjsc.v17.i10.109369
Published online Oct 26, 2025. doi: 10.4252/wjsc.v17.i10.109369
Synovial mesenchymal stem cell-derived exosomes delivering GRPEL1 activate PINK1-mediated mitophagy to promote cartilage repair in arthritis
Cheng-Hao Xiang, Hui-Long Zeng, Ze-Xing He, Zhang-Sheng Dai, Department of Orthopedics, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China
Li Zou, Department of Endocrinology, Minda Hospital of Hubei Minzu University, Enshi 445000, Hubei Province, China
Zhao-Gang Huang, Guo-Jun Zhang, Department of Orthopedics, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi 445000, Hubei Province, China
Author contributions: Xiang CH, Zou L, and Dai ZS wrote the first draft of this manuscript; Huang ZG, Zhang GJ, Zeng HL, and He ZX conducted to the material preparation, data collection and analysis. All authors contributed to the study conception and design, commented on previous versions of the manuscript, and read and approved the final manuscript.
Supported by the Scientific Research Project of the Traditional Chinese Medicine Administration of Hubei Provincial Health Commission, No. ZY2025 L268.
Institutional review board statement: This study was conducted in full compliance with the guidelines of the Ethics Review Committee of the Second Affiliated Hospital of Fujian Medical University and was approved under a formally registered research protocol, Approval No.[2025]090. Written informed consent was obtained from all participants before the study commenced.
Institutional animal care and use committee statement: This study was conducted in full compliance with the guidelines of the Ethics Review Committee of the Second Affiliated Hospital of Fujian Medical University and was approved under a formally registered research protocol, Approval No.[2025]090.
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 used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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: Zhang-Sheng Dai, Chief Physician, Department of Orthopedics, The Second Affiliated Hospital of Fujian Medical University, No. 950 Donghai Avenue, Quanzhou 362000, Fujian Province, China. daizhangsheng@126.com
Received: May 14, 2025
Revised: June 24, 2025
Accepted: September 4, 2025
Published online: October 26, 2025
Processing time: 164 Days and 23.9 Hours
Revised: June 24, 2025
Accepted: September 4, 2025
Published online: October 26, 2025
Processing time: 164 Days and 23.9 Hours
Core Tip
Core Tip: This study demonstrates that synovial mesenchymal stem cell-derived exosomes engineered to deliver GrpE-like 1 effectively enhance phosphatase and tensin homolog-induced putative kinase 1-mediated mitophagy, promoting cartilage repair in osteoarthritis. By integrating bioinformatics, in vitro chondrocyte assays, and in vivo rat models, the findings reveal a novel mechanism by which GrpE-like 1 activates mitochondrial quality control and reduces oxidative stress. This work introduces a promising exosome-based therapeutic strategy that targets mitochondrial dysfunction, advancing the development of disease-modifying treatments beyond current symptomatic approaches for osteoarthritis.