The miR-6779/XIAP axis alleviates IL-1β-induced chondrocyte senescence and extracellular matrix loss in osteoarthritis  

作　　者：Zongchao Li Aonan Dai Xiaoxiang Fang Kexing Tang Kun Chen Peng Gao Jingyue Su Xin Chen Shengwu Yang Zhenhan Deng Liangjun Li 

机构地区：[1]Department of Orthopaedics,The Affiliated Changsha Central Hospital,Hengyang Medical School,University of South China,Changsha,Hunan,China [2]Department of Orthopaedic Surgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,China [3]Geriatrics Center,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,China

出　　处：《Animal Models and Experimental Medicine》2025年第4期662-673,共12页动物模型与实验医学(英文)

基　　金：Natural Science Foundation of Changsha city,China,Grant/Award Number:kq2403166;Hunan Provincial Clinical Medical Technology Innovation Guiding Project,Grant/Award Number:2020SK53307;Basic Public Welfare Research projects of Wenzhou Science and Technology Bureau,Grant/Award Number:Y20240087;Natural Science Foundation of Hunan Province,Grant/Award Number:2020JJ8043;Start-up Funding for Talented Scientific Research of the First Affiliated Hospital of Wenzhou Medical University,Grant/Award Number:2023QD026;Key Project of Hunan Provincial Health Commission,Grant/Award Number:20201902 and C2019133;National Natural Science Foundation of China,Grant/Award Number:82472495。

摘　　要：Background:Osteoarthritis(OA)is a long-term degenerative joint disease worsen-ing over time.Aging and chondrocyte senescence contribute to OA progression.MicroRNAs have been confirmed to regulate different cellular processes.They con-tribute to OA pathology and may help to identify novel biomarkers and therapies for OA.Methods:This study used bioinformatics and experimental investigations to analyze and validate differentially expressed miRNAs in OA that might affect chondrocyte apoptosis and senescence.Results:miR-6779 was found to be significantly down-regulated in OA.Seventy-six of the predicted and miR-6779 targeted genes and the OA-associated disease genes overlapped,and these were enriched in cell proliferation,cell apoptosis,and cell cycle.miR-6779 overexpression remarkably attenuated IL-1βeffects on chon-drocytes by reducing MMP3 and MMP13 levels,promoting cell apoptosis,suppress-ing cell senescence,and increasing caspase-3,caspase-9 and reducing P16 and P21 levels.miR-6779 targeted inhibition of X-linked inhibitor of apoptosis protein(XIAP)expression.XIAP knockdown partially improved IL-1β-induced chondrocyte senes-cence and dysfunction.Lastly,when co-transfected with a miR-6779 agomir,the XIAP overexpression vector partially attenuated the effects of miR-6779 overexpression on chondrocytes;miR-6779 improved IL-1β-induced senescence and dysfunction in chondrocytes through targeting XIAP.Conclusion:miR-6779 is down-regulated,and XIAP is up-regulated in OA cartilage and IL-1β-treated chondrocytes.miR-6779 inhibits XIAP expression,thereby promot-ing senescent chondrocyte cell apoptosis and reducing chondrocyte senescence and ECM loss through XIAP.

关 键 词：CHONDROCYTE miR-6779 OSTEOARTHRITIS SENESCENCE X-linked inhibitor of apoptosis protein 

分 类 号：R684.3[医药卫生—骨科学]