Ni Chenzhe, Zhang Wanglin, Qiu Sai, Cheng Hao, Ma Chunhui
Department of Orthopaedics, Qidong People's Hospital, Nantong University, Jiangsu, 226200, China.
Department of Orthopaedics, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.
Curr Pharm Biotechnol. 2024;25(16):2166-2181. doi: 10.2174/0113892010275579240116061104.
Long non-coding RNAs (LncRNAs) are generally reported to participate in the development of Osteoarthritis (OA) by acting as competing endogenous RNAs (ceRNAs). However, the molecular mechanism is largely unknown. This study aimed to investigate the possible mechanisms contributing to osteoarthritis (OA).
Four gene expression profiles from patients with OA were downloaded from a public database and integrated to screen important RNAs associated with OA. Differentially expressed (DE) lncRNAs, microRNAs (miRNAs), and mRNAs were filtered, and a ceRNA network was constructed. An in vitro OA model was established by treating chondrocytes with IL-1β. The expression levels of MMP-13, COL2A1, aggrecan, and RUNX2 were detected by qRT-PCR and western blot. Cell proliferation ability was detected by CCK-8 assay. Flow cytometry was used for apoptosis assay. A dual luciferase reporter gene was used to confirm the relationship between DLEU1, miR-492, and .
An OA-related ceRNA network, including 11 pathways, 3 miRNAs, 7 lncRNAs, and 16 mRNAs, was constructed. DLEU1 and were upregulated, and miR-492 was downregulated in IL-1β-induced chondrocytes. Overexpression of DLEU1 suppressed viability and promoted apoptosis and extracellular matrix (ECM) degradation in IL-1β induced chondrocytes. Luciferase reporter assay validated the regulatory relations among DLEU1, miR-492, and . Further study revealed that the effects of DLEU1 on chondrocytes could be reversed by miR-492.
DLEU1 may be responsible for the viability, apoptosis, and ECM degradation in OA via miR-492/ axis.
长链非编码RNA（LncRNAs）通常被报道可作为竞争性内源RNA（ceRNAs）参与骨关节炎（OA）的发展。然而，其分子机制在很大程度上尚不清楚。本研究旨在探讨导致骨关节炎（OA）的可能机制。
从公共数据库下载4个骨关节炎患者的基因表达谱并进行整合，以筛选与OA相关的重要RNA。筛选差异表达（DE）的lncRNAs、微小RNA（miRNAs）和信使RNA（mRNAs），并构建ceRNA网络。通过用白细胞介素-1β（IL-1β）处理软骨细胞建立体外OA模型。采用qRT-PCR和蛋白质免疫印迹法检测基质金属蛋白酶-13（MMP-13）、Ⅱ型胶原α1链（COL2A1）、聚集蛋白聚糖和Runx2转录因子（RUNX2）的表达水平。采用细胞计数试剂盒-8（CCK-8）法检测细胞增殖能力。采用流式细胞术进行细胞凋亡检测。使用双荧光素酶报告基因来确认DLEU1、miR-492和[此处原文缺失某个基因]之间的关系。
构建了一个与OA相关的ceRNA网络，包括11条通路、3个miRNAs、7个lncRNAs和16个mRNAs。在IL-1β诱导的软骨细胞中，DLEU1和[此处原文缺失某个基因]上调，而miR-492下调。DLEU1的过表达抑制了IL-1β诱导的软骨细胞的活力，促进了细胞凋亡和细胞外基质（ECM）降解。荧光素酶报告基因检测验证了DLEU1、miR-492和[此处原文缺失某个基因]之间的调控关系。进一步研究表明，miR-492可逆转DLEU1对软骨细胞的影响。
DLEU1可能通过miR-492/[此处原文缺失某个基因]轴参与OA中细胞活力、细胞凋亡和ECM降解的过程。
