Chen LQ, Ma S, Yu J, Zuo DC, Yin ZJ, Li FY, He X, Peng HT, Shi XQ, Huang WJ, Li Q, Wang J. Human umbilical cord mesenchymal stem cell-derived exosomal miR-199a-3p inhibits the MAPK4/NF-κB signaling pathway to relieve osteoarthritis. World J Stem Cells 2025; 17(4): 103919 [DOI: 10.4252/wjsc.v17.i4.103919]
Corresponding Author of This Article
Jing Wang, Department of Rheumatology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming 650032, Yunnan Province, China. wangjing201456@163.com
Research Domain of This Article
Orthopedics
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/
Ling-Qiang Chen, Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
Sha Ma, Juan Yu, Da-Chen Zuo, Zi-Jing Yin, Fa-You Li, Xia He, Hai-Ting Peng, Xiao-Qing Shi, Wei-Juan Huang, Qin Li, Jing Wang, Department of Rheumatology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan Province, China
Author contributions: Chen LQ and Wang J contributed to the project administration and resources; Chen LQ and Ma S contributed to the validation; Chen LQ and Yu J contributed to the visualization of this manuscript; Chen LQ contributed to conceptualization and writing original draft of the manuscript; Ma S and Yu J contributed to data curation; Zuo DC and Yin ZJ contributed to formal analysis; Wang J contributed to funding acquisition, investigation, and writing review and editing; Li FY and He X contributed to methodology; Peng HT and Shi XQ contributed to software; Huang WJ and Li Q contributed to supervision of this manuscript. All authors have read and approved the final manuscript.
Supported by Basic Research Plan of Yunnan Province, No. 202201AT070059; National Natural Science Foundation of China, No. 81760407; Science and Technology Talent and Platform Plan of Yunnan Provincial Department of Science and Technology, No. 202205AC160066.
Institutional animal care and use committee statement: All procedures involving animals are reviewed and approved by the Experimental Animal Ethics Committee of Kunming University of Science and Technology.
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: Jing Wang, Department of Rheumatology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming 650032, Yunnan Province, China. wangjing201456@163.com
Received: December 16, 2024 Revised: January 25, 2025 Accepted: March 13, 2025 Published online: April 26, 2025 Processing time: 130 Days and 21.3 Hours
Abstract
BACKGROUND
There is currently no effective treatment for osteoarthritis (OA), which is the most common joint disorder leading to disability. Although human umbilical cord mesenchymal stem cells (hUC-MSCs) are promising OA treatments, their use is limited by the condition itself, and understanding of the underlying mechanisms of OA is lacking.
AIM
To explore the specific molecular mechanism by which hUC-MSC-derived exosomal miR-199a-3p improves OA.
METHODS
Sodium iodoacetate was injected into rat articulations to construct an animal model of OA. Interleukin (IL)-1β was used to induce human chondrocytes (CHON-001) to construct an OA chondrocyte model. Exosomes in hUC-MSCs were isolated using Ribo™ Exosome Isolation Reagent. Real-time reverse transcriptase-polymerase chain reaction and western blotting were used to detect the expression of related genes and proteins, and damage to CHON-001 cells and rat articular cartilage tissue was evaluated by enzyme-linked immunosorbent assay, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling staining and hematoxylin and eosin staining.
RESULTS
hUC-MSC-derived exosomes (hUC-MSC-Exos) inhibited the expression of IL-1β-induced inflammatory cytokines, namely, IL-6, IL-8 and tumor necrosis factor-α. hUC-MSC-Exos also improved the viability but inhibited the apoptosis of CHON-001 cells, improved the pathological condition of articular cartilage tissue and alleviated the development of OA in vivo. Mechanistically, hUC-MSC-Exos downregulated the expression of mitogen-activated protein kinase 4 by delivering miR-199a-3p, thereby inhibiting the activation of the nuclear factor-kappaB signaling pathway, alleviating IL-1β-induced chondrocyte inflammation and apoptosis, and ultimately improving the development of OA.
CONCLUSION
hUC-MSC-derived exosomal miR-199a-3p alleviates OA by inhibiting the mitogen-activated protein kinase 4/nuclear factor-kappaB signaling pathway. The present findings suggest that miR-199a-3p delivery by hUC-MSC-Exos may be a novel strategy for the treatment of OA.
Core Tip: Osteoarthritis (OA), a debilitating joint disorder, currently lacks effective treatment options. This study reveals that exosomal miR-199a-3p derived from human umbilical cord mesenchymal stem cells offers a novel therapeutic strategy for OA. By targeting the mitogen-activated protein kinase 4/nuclear factor-kappaB signaling pathway, miR-199a-3p significantly reduces inflammation and inhibits apoptosis in chondrocytes. These findings highlight the potential of exosomal miR-199a-3p delivery as a promising approach for managing OA, providing a foundation for future clinical applications.
