Borgonio Cuadra Verónica M, González-Huerta Norma Celia, Romero-Córdoba Sandra, Hidalgo-Miranda Alfredo, Miranda-Duarte Antonio
Department of Genetics, Instituto Nacional de Rehabilitación (INR), Mexico City, Mexico.
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
PLoS One. 2014 Jun 5;9(6):e97690. doi: 10.1371/journal.pone.0097690. eCollection 2014.
To analyze a set of circulating microRNA (miRNA) in plasma from patients with primary Osteoarthritis (OA) and describe the biological significance of altered miRNA in OA based on an in silico analysis of their target genes.
miRNA expression was analyzed using TaqMan Low Density Arrays and independent assays. The search for potential messenger RNA (mRNA) targets of the differentially expressed miRNA was performed by means of the miRWalk and miRecords database; we conducted the biological relevance of the predicted miRNA targets by pathway analysis with the Reactome and DAVID databases.
We measured the expression of 380 miRNA in OA; 12 miRNA were overexpressed under the OA condition (p value, ≤0.05; fold change, >2). These results were validated by the detection of some selected miRNA by quantitative PCR (qPCR). In silico analysis showed that target messenger RNA (mRNA) were potentially regulated by these miRNA, including genes such as SMAD1, IL-1B, COL3A, VEGFA, and FGFR1, important in chondrocyte maintenance and differentiation. Some metabolic pathways affected by the miRNA: mRNA ratio are signaling Bone morphogenetic proteins (BMP), Platelet-derived growth factor (PDGF), and Nerve growth factor (NGF), these latter two involved in the process of pain.
We identified 12 miRNA in the plasma of patients with primary OA. Specific miRNA that are altered in the disease could be released into plasma, either due to cartilage damage or to an inherent cellular mechanism. Several miRNA could regulate genes and pathways related with development of the disease; eight of these circulating miRNA are described, to our knowledge, for first time in OA.
分析原发性骨关节炎（OA）患者血浆中的一组循环微小RNA（miRNA），并基于对其靶基因的计算机分析描述OA中miRNA改变的生物学意义。
使用TaqMan低密度阵列和独立检测法分析miRNA表达。通过miRWalk和miRecords数据库搜索差异表达miRNA的潜在信使核糖核酸（mRNA）靶标；我们使用Reactome和DAVID数据库通过通路分析对预测的miRNA靶标的生物学相关性进行了研究。
我们检测了OA患者中380种miRNA的表达；12种miRNA在OA条件下过表达（p值≤0.05；倍数变化>2）。通过定量PCR（qPCR）检测一些选定的miRNA验证了这些结果。计算机分析表明，靶信使核糖核酸（mRNA）可能受这些miRNA调控，包括SMAD1、IL-1B、COL3A、VEGFA和FGFR1等基因，这些基因在软骨细胞维持和分化中起重要作用。受miRNA:mRNA比率影响的一些代谢途径包括骨形态发生蛋白（BMP）、血小板衍生生长因子（PDGF）和神经生长因子（NGF）信号通路，后两者参与疼痛过程。
我们在原发性OA患者血浆中鉴定出12种miRNA。疾病中改变的特定miRNA可能由于软骨损伤或内在细胞机制而释放到血浆中。几种miRNA可能调控与疾病发展相关的基因和途径；据我们所知，其中8种循环miRNA在OA中首次被描述。
