Ding ZC, He JJ, Shi LZ, Qian J, Mei SH, Kang X, Chen JW. Fibro-adipogenic progenitors prevent skeletal muscle degeneration at acute phase upon tendon rupture in a murine tibialis anterior tenotomy model. World J Stem Cells 2025; 17(6): 105491 [DOI: 10.4252/wjsc.v17.i6.105491]
Corresponding Author of This Article
Ji-Wu Chen, MD, PhD, Chief Physician, Professor, Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, No. 85 Wujin Road, Shanghai 200080, China. jeevechen@gmail.com
Research Domain of This Article
Sport Sciences
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Zhe-Ci Ding, Lu-Ze Shi, Ji-Wu Chen, Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
Juan-Juan He, Shu-Hao Mei, Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China
Jin Qian, Department of Orthopaedics, Guangdong Provincial People’s Hospital, Southern Medical University, Guangzhou 510080, Guangdong Province, China
Xia Kang, Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
Co-first authors: Zhe-Ci Ding and Juan-Juan He.
Co-corresponding authors: Xia Kang and Ji-Wu Chen.
Author contributions: Ding ZC and He JJ contributed equally to this manuscript as co-first authors of this manuscript. Ding ZC, He JJ, Shi LZ, and Qian J contributed to the acquisition of data; Ding ZC, He JJ, and Mei SH were responsible for analysis and interpretation of data; Ding ZC drafted the work; Chen JW revised the manuscript; Kang X and Chen JW made contributions to the conception and design of the work, they contributed equally to this manuscript as co-corresponding authors.
Supported by National Natural Science Foundation of China, No. 82172509.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals. The study was approved by the Institutional Animal Care and Use Committee of Shanghai General Hospital, No. 2023AW045.
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: No additional data are available.
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: Ji-Wu Chen, MD, PhD, Chief Physician, Professor, Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, No. 85 Wujin Road, Shanghai 200080, China. jeevechen@gmail.com
Received: January 27, 2025 Revised: March 7, 2025 Accepted: June 10, 2025 Published online: June 26, 2025 Processing time: 151 Days and 18.5 Hours
Abstract
BACKGROUND
Fibro-adipogenic progenitors (FAPs) are a group of mesenchymal stem cells that cause fibro-fatty degeneration in skeletal muscle in various chronic disease models. FAPs also play a role in preventing muscle degeneration at acute stages during disease progression. However, few studies have reported the changes in and function of FAPs in the acute phase after tendon rupture.
AIM
To clarify the changes in the number of FAPs and their impact on skeletal muscle soon after tendon rupture to facilitate future studies targeting FAPs to treat muscle degeneration.
METHODS
We utilized Pdgfra-H2B::eGFP mice to trace and quantify FAPs in a tibialis anterior tenotomy (TAT) model at 0 and 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, and 6 weeks post-injury, and the results were further validated using fluorescence-activated cell sorting analysis with C57BL/6 mice at the same post-injury timepoints. We subsequently used PdgfraCreERT::RosaDTA mice, and evaluated the severity of post-TAT skeletal muscle degeneration with or without FAP-depletion.
RESULTS
The number of FAPs peaked at 1 week post-TAT before gradually declining to a level comparable to that pre-TAT. The change in the number of FAPs was potentially temporally correlated with the progression of skeletal muscle degeneration after TAT. FAP-depletion led to more severe degeneration early after TAT, indicating that FAPs potentially alleviate muscle degeneration after tendon rupture in the early post-injury phase.
CONCLUSION
FAPs potentially alleviate the degeneration of skeletal muscle in the acute stage after tendon rupture.
Core Tip: In this study, we demonstrate that fibro-adipogenic progenitors (FAPs) may actually attenuate early-stage degenerative processes following tendon rupture. To our knowledge, this represents the first investigation into the role of FAPs in early-stage skeletal muscle degeneration post-tendon rupture. Our work elucidates the dynamic changes in FAPs population and function during the early phases of muscle degeneration following tendon rupture, providing a more comprehensive understanding of FAPs biology in this context. These findings offer valuable insights for future research on therapeutic interventions and preventive strategies for post-rupture muscle degeneration.
