CircADAMTS6/miR-431-5p axis regulate interleukin-1β induced chondrocyte apoptosis
CircADAMTS6/miR-431-5p axis regulate interleukin-1β induced chondrocyte apoptosis
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DOI：
10.1002/jgm.3304
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发表时间：
2021-01-20
影响因子：
3.5
通讯作者：
Zhu, Jun
中科院分区：
文献类型：
--
作者：
Fu, Qiwei;Li, Lexiang;Zhu, Jun
背景越来越多的证据表明，环状RNA(CircRNAs)参与了骨关节炎的发生发展。本研究旨在探讨CircADAMTS6/miR-431-5p轴在调节白细胞介素1β(IL-1β)诱导软骨细胞凋亡中的作用。然后，进行生物信息学分析以确定CircADAMTS6的作用和功能。用干扰RNA表达或过表达的小分子慢病毒载体转导软骨细胞。用Annexin-V-异硫氰酸荧光素(FITC)双染色法检测各组软骨细胞凋亡率。结果经IL-1β处理后，CircADAMTS6与miR-431-5的表达下调。Annexin-V-FITC双重染色显示，CircADAMTS6过表达抑制了人软骨细胞的凋亡。而过表达miR-431-5p则有相反的作用。双荧光素酶报告实验表明，CircADAMTS6可与miR-431-5直接结合。结论CircADAMTS6/miR-431-5p轴是OA的新靶点。生物信息学分析表明，CircADAMTS6是miR-431-5P的海绵。
Background Growing evidence suggests that circular RNAs (circRNAs) are involved in the development of osteoarthritis (OA). The present study aimed to explore the CircADAMTS6/miR-431-5p axis with respect to regulating interleukin-1 beta (IL-1 beta) induced chondrocyte apoptosis.Methods We first evaluated the differentially expressed circRNAs between normal chondrocytes and interleukin (IL)-1 beta-stimulated chondrocytes. Then, bioinformatic analysis was performed to identify the role and function of circADAMTS6. Small interfering RNA-expressing or overexpressing circADAMTS6 lentiviral vectors were used for transduction of chondrocytes. Annexin-V-fluorescein isothiocyanate (FITC) double staining was performed to measure the apoptotic rate of the chondrocytes in each group. Finally, a dual luciferase reporter assay was performed to identify the target relationship between circADAMTS6 and miR-431-5p.Results After treatment with IL-1 beta, circADAMTS6 was down-regulated compared to the normal chondrocyte group. The overexpression of circADAMTS6 inhibited apoptosis in human chondrocytes, as indicated by annexin-V-FITC double staining. However, overexpression of miR-431-5p had the opposite effect. A dual luciferase reporter assay indicated that circADAMTS6 could directly binding with miR-431-5p.Conclusions Our findings demonstrate that the circADAMTS6/miR-431-5p axis comprises a new target for OA. Bioinformatic analysis suggested that circADAMTS6 acted as a sponge of miR-431-5p.