衰老
氧化应激
变性(医学)
下调和上调
椎间盘
生物
细胞生物学
表型
氧化磷酸化
细胞外基质
生物信息学
癌症研究
医学
病理
遗传学
基因
解剖
生物化学
作者
Jianle Wang,Dongdong Xia,Yan Lin,Wenbin Xu,Yaosen Wu,Jiaoxiang Chen,Junjie Chu,Pengcheng Shen,She-Ji Weng,Xiangyang Wang,Lifeng Shen,Shunwu Fan,Shuying Shen
标识
DOI:10.1038/s12276-022-00732-0
摘要
Low back pain, triggered by intervertebral disc degeneration (IVDD), is one of the most common causes of disability and financial expenditure worldwide. However, except for surgical interventions, effective medical treatment to prevent the progression of IVDD is lacking. This study aimed to investigate the effects of circKIF18A, a novel circRNA, on IVDD progression and to explore its underlying mechanism in IVDD. In this study, we found that oxidative stress was positively correlated with nucleus pulposus cell (NPC) senescence in IVDD and that circKIF18A was downregulated in IVDD and attenuated senescent phenotypes such as cell cycle arrest and extracellular matrix degradation in NPCs. Mechanistically, circKIF18A competitively suppressed ubiquitin-mediated proteasomal degradation of MCM7, and the protective effects of circKIF18A on NPCs were partially mediated by MCM7 under oxidative stress. Intradiscal injection of adenoviral circKIF18A ameliorated IVDD in a rat model. This study revealed that circKIF18A regulates NPC degeneration by stabilizing MCM7 and identified a novel signaling pathway, the circKIF18A-MCM7 axis, for anti-senescence molecular therapy in IVDD.
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