Yijie Chen, Wenqi Sha, Yifan Zhang, Wanyi Kou, Liu Yang, Ruixin Guo, Chenyang Li, Junjie Zhao, Zhenghui Wang
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引用次数: 0
Abstract
Objective: Dysregulation of chondrogenic differentiation is associated with osteoarthritis (OA). The myokine irisin is beneficial in OA treatment; yet, the underlying mechanism is not fully understood. Long noncoding RNAs (lncRNAs) act as important regulators of chondrocyte differentiation. This study was conducted to address the role of lncRNAs in mediating irisin-induced chondrocyte differentiation.
Methods: We investigated the irisin-regulated lncRNA profile change in human mesenchymal stem cells (MSCs) using published whole transcriptome sequencing data. We predicted their potential targets and competitive endogenous RNA (ceRNA) prediction and analyzed their molecular functions using functional enrichment analysis.
Results: More differentially expressed lncRNAs (DElncRNAs) were observed in irisin-treated samples. The top irisin-induced lncRNAs were associated with OA or chondrogenic differentiation, including XIST, PAX8-AS1, CASC15, LINC01618, and DLX6-AS1. The DEGs co-expressed with DElncRNAs were enriched in skeletal system development, extracellular matrix (ECM) organization, cell adhesion, and inflammation associated pathways. Several lncRNAs likely acted as ceRNAs to regulate downstream mRNAs including ROR2 and SORBS1 in in OA or chondrogenic differentiation.
Conclusions: We demonstrate the global regulation of lncRNAs by irisin during chondrogenic differentiation of human MSCs. Further study is required to characterize the key irisin-regulated lncRNAs in chondrogenic differentiation.
目的:软骨分化失调与骨关节炎(OA)有关。肌动蛋白鸢尾素有益于 OA 的治疗,但其潜在机制尚未完全明了。长非编码 RNA(lncRNA)是软骨细胞分化的重要调节因子。本研究旨在探讨lncRNAs在介导鸢尾素诱导的软骨细胞分化中的作用:方法:我们利用已发表的全转录组测序数据研究了人间质干细胞(MSCs)中鸢尾素调控的lncRNA谱系变化。我们预测了它们的潜在靶标和竞争性内源性 RNA(ceRNA),并利用功能富集分析法分析了它们的分子功能:结果:在鸢尾素处理的样本中观察到了更多的差异表达lncRNAs(DElncRNAs)。鸢尾素诱导的最主要lncRNA与OA或软骨分化有关,包括XIST、PAX8-AS1、CASC15、LINC01618和DLX6-AS1。与DElncRNAs共表达的DEGs富集在骨骼系统发育、细胞外基质(ECM)组织、细胞粘附和炎症相关通路中。一些lncRNA可能作为ceRNA调控下游mRNA,包括OA或软骨分化过程中的ROR2和SORBS1:我们证明了鸢尾素在人类间充质干细胞软骨源分化过程中对lncRNAs的全局调控。我们还需要进一步的研究来确定在软骨源分化过程中鸢尾素调控的关键lncRNA。
期刊介绍:
Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.