Human umbilical cord mesenchymal stem cell-derived exosomal miR-199a-3p inhibits the MAPK4/NF-κB signaling pathway to relieve osteoarthritis  

作　　者：Ling-Qiang Chen 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 

机构地区：[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

出　　处：《World Journal of Stem Cells》2025年第4期113-135,共23页世界干细胞杂志(英文)

基　　金：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.

摘　　要：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)-1βwas 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 tripho-sphate-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-MSCExos may be a novel strategy for the treat

关 键 词：OSTEOARTHRITIS Human umbilical cord mesenchymal stem cells EXOSOMES MiR-199a-3p Mitogen-activated protein kinase 4 Nuclear factor-kappaB 

分 类 号：R684.3[医药卫生—骨科学]