DOI: 10.1002/ame2.12529
The miR-6779/XIAP axis alleviates IL-1β-induced chondrocyte senescence and extracellular matrix loss in osteoarthritis
Zongchao Li1
Aonan Dai1
Xiaoxiang Fang1
Kexing Tang1
Kun Chen1
Peng Gao1
Jingyue Su2
Xin Chen2
Shengwu Yang2
Zhenhan Deng2
Liangjun Li1
1.Department of Orthopaedics,The Affiliated Changsha Central Hospital,Hengyang Medical School,University of South China,Changsha,Hunan,China2.Department of Orthopaedic Surgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,China;Geriatrics Center,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,China
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-1β effects 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.
机标关键词：senescencematrixxiapaxislossalleviateschondrocyteextracellular
论文发表日期：2025-04-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：12( 662-673 )
英文信息