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环状RNA_0075048沉默通过与miR-663b结合来调节LCP1,从而改善白细胞介素-1β诱导的软骨细胞损伤。

circ_0075048 silencing regulates LCP1 to improve IL-1β-induced chondrocyte injury by binding with miR-663b.

作者信息

Zhang Pin, Pei Ru, Shen Quanhu

机构信息

Department of Orthopedics, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, 223800, Jiangsu, China.

出版信息

J Orthop Surg Res. 2025 Jan 9;20(1):24. doi: 10.1186/s13018-025-05449-0.

Abstract

BACKGROUND

Osteoarthritis (OA) is a common type of degenerative arthropathy. Previous studies have demonstrated that circular RNAs (circRNAs) are involved in the progression of OA. This study aimed to investigate the role and associated mechanism of circ_0075048 in OA.

METHODS

The expression of circ_0075048 was analyzed based on the Gene Expression Omnibus dataset GSE178724. Human chondrocytes were stimulated with IL-1β to establish an in vitro OA model. Bioinformatic analysis was performed to identify target genes of circ_0075048. The expression of circ_0075048, miR-663b, and LCP1 was detected by quantitative reverse transcription-polymerase chain reaction. The cell viability and apoptosis of C28/I2 cells were determined using Cell Counting Kit-8 assay and flow cytometry. Protein expression was detected using western blotting.

RESULTS

The expression of circ_0075048 was up-regulated in IL-1β-induced chondrocytes. circ_0075048 silencing promoted the viability of and inhibited the apoptosis of and extracellular matrix (ECM) production of chondrocytes. circ_0075048 was found to be a sponge of miR-663b and LCP1 was found to be a target of miR-663b. circ_0075048 silencing increased miR-663b expression but decreased LCP1 expression levels in chondrocytes. An miR-663b inhibitor eliminated the protective effect of a circ_0075048 small interfering RNA (siRNA) on chondrocytes. However, an LCP1 siRNA abolished the effect of the miR-663b inhibitor on chondrocytes.

CONCLUSION

circ_0075048 silencing inhibited the apoptosis of and ECM degradation in IL-1β-induced chondrocytes by regulating miR-663b/LCP1 axis.

摘要

背景

骨关节炎(OA)是一种常见的退行性关节病。先前的研究表明,环状RNA(circRNAs)参与OA的进展。本研究旨在探讨circ_0075048在OA中的作用及相关机制。

方法

基于基因表达综合数据库GSE178724分析circ_0075048的表达。用白细胞介素-1β刺激人软骨细胞以建立体外OA模型。进行生物信息学分析以鉴定circ_0075048的靶基因。通过定量逆转录-聚合酶链反应检测circ_0075048、miR-663b和LCP1的表达。使用细胞计数试剂盒-8检测法和流式细胞术测定C28/I2细胞的活力和凋亡。使用蛋白质免疫印迹法检测蛋白质表达。

结果

circ_0075048在白细胞介素-1β诱导的软骨细胞中表达上调。circ_0075048沉默促进软骨细胞的活力,抑制其凋亡和细胞外基质(ECM)产生。发现circ_0075048是miR-663b的海绵,且LCP1是miR-663b的靶标。circ_0075048沉默增加软骨细胞中miR-663b的表达,但降低LCP1的表达水平。miR-663b抑制剂消除了circ_0075048小干扰RNA(siRNA)对软骨细胞的保护作用。然而,LCP1 siRNA消除了miR-663b抑制剂对软骨细胞的作用。

结论

circ_0075048沉默通过调节miR-663b/LCP1轴抑制白细胞介素-1β诱导的软骨细胞凋亡和ECM降解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc2/11715223/a50e2e9db3d4/13018_2025_5449_Fig1_HTML.jpg

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