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膝骨关节炎患者与正常个体软骨中长链非编码RNA的表达谱

Expression profiles of long non-coding RNAs in the cartilage of patients with knee osteoarthritis and normal individuals.

作者信息

Liu Yanchang, Jing Juehua, Yu Haoran, Zhang Jisen, Cao Qiliang, Zhang Xin, Liu Jianjun, Zhang Shuo, Cheng Wendan

机构信息

Department of Orthopedic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China.

出版信息

Exp Ther Med. 2021 Apr;21(4):365. doi: 10.3892/etm.2021.9796. Epub 2021 Feb 18.

Abstract

Knee osteoarthritis is caused by a multifactorial imbalance in the synthesis and degradation of knee chondrocytes, subchondral bone and extracellular matrix. Abnormal expression of long non-coding RNAs (lncRNAs) affects the metabolism, synovitis, autophagy and apoptosis of chondrocytes, as well as the production of cartilage matrix. The aim of the present study was to identify novel targets for the treatment of osteoarthritis and to examine the pathogenesis of the disease. The lncRNA expression profiles of seven patients with knee osteoarthritis and six healthy controls were examined by RNA-sequencing. Differentially expressed lncRNAs were selected for bioinformatics analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Reverse transcription-quantitative PCR (RT-qPCR) was used to further investigate the differential expression of the lncRNAs. A total of 23,583 lncRNAs were identified in osteoarthritis cartilage, including 5,255 upregulated and 5,690 downregulated lncRNAs, compared with normal cartilage. Although there were more downregulated lncRNAs compared with upregulated lncRNAs, among the changed lncRNAs (fold-change >6), there were more upregulated lncRNAs compared with downregulated lncRNAs. Several lncRNAs exhibiting differences were identified as potential therapeutic targets in knee osteoarthritis. GO and KEGG pathway analyses were performed for the target genes of the differentially expressed lncRNAs. RT-qPCR validation was performed on three randomly selected upregulated and downregulated lncRNAs. The results of RT-qPCR were consistent with the findings obtained by RNA-sequencing analysis. The findings from the present study may contribute to the diagnosis of osteoarthritis and may predict the development of osteoarthritis. Furthermore, the differentially expressed lncRNAs may aid in the identification of novel candidate targets for the treatment of knee osteoarthritis.

摘要

膝关节骨关节炎是由膝关节软骨细胞、软骨下骨和细胞外基质合成与降解的多因素失衡引起的。长链非编码RNA(lncRNA)的异常表达影响软骨细胞的代谢、滑膜炎、自噬和凋亡,以及软骨基质的产生。本研究的目的是确定骨关节炎治疗的新靶点,并研究该疾病的发病机制。通过RNA测序检测了7例膝关节骨关节炎患者和6例健康对照的lncRNA表达谱。选择差异表达的lncRNA进行生物信息学分析,包括基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。采用逆转录定量PCR(RT-qPCR)进一步研究lncRNA的差异表达。与正常软骨相比,在骨关节炎软骨中共鉴定出23583个lncRNA,其中5255个上调,5690个下调。虽然下调的lncRNA比上调的lncRNA多,但在变化的lncRNA中(倍数变化>6),上调的lncRNA比下调的lncRNA多。几种表现出差异的lncRNA被确定为膝关节骨关节炎的潜在治疗靶点。对差异表达lncRNA的靶基因进行了GO和KEGG通路分析。对三个随机选择的上调和下调lncRNA进行了RT-qPCR验证。RT-qPCR结果与RNA测序分析结果一致。本研究结果可能有助于骨关节炎的诊断,并可能预测骨关节炎的发展。此外,差异表达的lncRNA可能有助于识别膝关节骨关节炎治疗的新候选靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c90/7903471/7c46509ac2bb/etm-21-04-09796-g00.jpg

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