Hsa_circ_0004662 Accelerates the Progression of Osteoarthritis via the microRNA-424-5p/VEGFA Axis.

IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-01-01 DOI:10.2174/1566524023666221103161203

Wei Xie, Luoyong Jiang, Xiaoyang Huang, Wei You, Wei Sun

{"title":"Hsa_circ_0004662 Accelerates the Progression of Osteoarthritis via the microRNA-424-5p/VEGFA Axis.","authors":"Wei Xie, Luoyong Jiang, Xiaoyang Huang, Wei You, Wei Sun","doi":"10.2174/1566524023666221103161203","DOIUrl":null,"url":null,"abstract":"Objective: Circular RNAs (circRNAs) have been extensively implicated in osteoarthritis (OA) progression. Therefore, this study explores the impact of hsa_circ_0004662 on OA progression and the related molecular mechanism.Methods: Human articular chondrocyte injury was induced by IL-1β to construct the OA model in vitro. Hsa_circ_0004662 and microRNA (miR)-424-5p expression in chondrocytes was evaluated with qRT-PCR. Vascular endothelial growth factors A (VEGFA) expression was examined with qRT-PCR and western blot after hsa_circ_0004662 knockdown or miR-424-5p overexpression in chondrocytes. Subsequent to loss- and gain-of-function assays in IL-1β-induced chondrocytes, the proliferation and apoptosis of chondrocytes were assessed with CCK-8 assay and flow cytometry, respectively. The expression of MMP13, Aggrecan, and apoptosis-related proteins Bax and Bcl-2 was measured with western blot. The binding of miR-424-5p to hsa_circ_0004662 and VEGFA was assessed with a dual-luciferase reporter gene assay.Results: Hsa_circ_0004662 was up-regulated, but miR-424-5p was down-regulated in IL-1β-induced chondrocytes. Mechanistically, both hsa_circ_0004662 and VEGFA bound to miR-424-5p, and hsa_circ_0004662 enhanced VEGFA expression by downregulating miR-424-5p. Hsa_circ_0004662 knockdown elevated cell proliferation, decreased apoptosis and MMP13 and Bax expression, and increased Aggrecan and Bcl- 2 expression in IL-1β-induced chondrocytes, which was counteracted by further miR- 424-5p down-regulation or VEGFA overexpression.Conclusion: Hsa_circ_0004662 facilitates OA progression via the miR-424-5p/ VEGFA axis.","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"217-225"},"PeriodicalIF":4.7000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1566524023666221103161203","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: Circular RNAs (circRNAs) have been extensively implicated in osteoarthritis (OA) progression. Therefore, this study explores the impact of hsa_circ_0004662 on OA progression and the related molecular mechanism.

Methods: Human articular chondrocyte injury was induced by IL-1β to construct the OA model in vitro. Hsa_circ_0004662 and microRNA (miR)-424-5p expression in chondrocytes was evaluated with qRT-PCR. Vascular endothelial growth factors A (VEGFA) expression was examined with qRT-PCR and western blot after hsa_circ_0004662 knockdown or miR-424-5p overexpression in chondrocytes. Subsequent to loss- and gain-of-function assays in IL-1β-induced chondrocytes, the proliferation and apoptosis of chondrocytes were assessed with CCK-8 assay and flow cytometry, respectively. The expression of MMP13, Aggrecan, and apoptosis-related proteins Bax and Bcl-2 was measured with western blot. The binding of miR-424-5p to hsa_circ_0004662 and VEGFA was assessed with a dual-luciferase reporter gene assay.

Results: Hsa_circ_0004662 was up-regulated, but miR-424-5p was down-regulated in IL-1β-induced chondrocytes. Mechanistically, both hsa_circ_0004662 and VEGFA bound to miR-424-5p, and hsa_circ_0004662 enhanced VEGFA expression by downregulating miR-424-5p. Hsa_circ_0004662 knockdown elevated cell proliferation, decreased apoptosis and MMP13 and Bax expression, and increased Aggrecan and Bcl- 2 expression in IL-1β-induced chondrocytes, which was counteracted by further miR- 424-5p down-regulation or VEGFA overexpression.

Conclusion: Hsa_circ_0004662 facilitates OA progression via the miR-424-5p/ VEGFA axis.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

Hsa_circ_0004662通过microRNA-424-5p/VEGFA轴加速骨关节炎的进展。

目的：环状核糖核酸（circRNAs）被广泛认为与骨关节炎（OA）的进展有关。方法：用 IL-1β 诱导人关节软骨细胞损伤，在体外构建 OA 模型。用 qRT-PCR 评估软骨细胞中 Hsa_circ_0004662 和 microRNA (miR)-424-5p 的表达。在软骨细胞中敲除 hsa_circ_0004662 或过表达 miR-424-5p 后，用 qRT-PCR 和 western 印迹法检测血管内皮生长因子 A (VEGFA) 的表达。在 IL-1β 诱导的软骨细胞中进行功能缺失和功能增益实验后，分别用 CCK-8 检测法和流式细胞术评估软骨细胞的增殖和凋亡。用 Western 印迹法测定了 MMP13、Aggrecan 以及凋亡相关蛋白 Bax 和 Bcl-2 的表达。采用双荧光素酶报告基因检测法评估了 miR-424-5p 与 hsa_circ_0004662 和 VEGFA 的结合情况：结果：在IL-1β诱导的软骨细胞中，Hsa_circ_0004662上调，但miR-424-5p下调。从机理上讲，hsa_circ_0004662和VEGFA都与miR-424-5p结合，hsa_circ_0004662通过下调miR-424-5p来增强VEGFA的表达。在 IL-1β 诱导的软骨细胞中，Hsa_circ_0004662 的敲除可促进细胞增殖，减少细胞凋亡和 MMP13 及 Bax 的表达，增加 Aggrecan 和 Bcl- 2 的表达，而进一步的 miR- 424-5p 下调或 VEGFA 的过表达可抵消这种效应：结论：Hsa_circ_0004662通过miR-424-5p/ VEGFA轴促进OA进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464

期刊介绍： ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.