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 Apr 26;17(4):103919. doi: 10.4252/wjsc.v17.i4.103919.
Ling-Qiang Chen  1 ,  Sha Ma  2 ,  Juan Yu  2 ,  Da-Chen Zuo  2 ,  Zi-Jing Yin  2 ,  Fa-You Li  2 ,  Xia He  2 ,  Hai-Ting Peng  2 ,  Xiao-Qing Shi  2 ,  Wei-Juan Huang  2 ,  Qin Li  2 ,  Jing Wang  3
Affiliations
  • 1. Department of Orthopedics, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China.
  • 2. 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.
  • 3. 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. [email protected].
PMID: 40308884 DOI: 10.4252/wjsc.v17.i4.103919
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.

Keywords
Exosomes; Human umbilical cord mesenchymal stem cells; MiR-199a-3p; Mitogen-activated protein kinase 4; Nuclear factor-kappaB; Osteoarthritis.
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