Characterization of microRNA expression profiles in normal and osteoarthritic human chondrocytes.
Characterization of microRNA expression profiles in normal and osteoarthritic human chondrocytes.
复制标题
DOI：
10.1186/1471-2474-13-144
复制
发表时间：
2012-08-12
影响因子：
2.3
通讯作者：
Blanco FJ
中科院分区：
文献类型：
--
作者：
Díaz-Prado S;Cicione C;Muiños-López E;Hermida-Gómez T;Oreiro N;Fernández-López C;Blanco FJ
骨关节炎（OA）是一种多因素疾病，其特征是由于环境、机械和遗传因素导致的关节软骨破坏。OA的遗传学是复杂的，尚未完全了解。最近的工作已经证明了microRNAs（miRNAs）在软骨功能中的重要性。miRNAs是一类调控基因表达的非编码小分子RNA，参与细胞凋亡、增殖、发育、糖脂代谢等多种细胞过程。本研究的目的是鉴定和表征正常和OA软骨细胞中miRNA的表达谱，并确定它们在OA中的作用。将软骨细胞移至聚集体培养物中，并使用组织学和qPCR技术进行评价。使用Agilent Human miRNA Microarray分离并分析miRNA。在分析的723个miRNAs中，7个miRNAs显示出统计学显著的差异表达。在这7种人miRNA中，1种在OA软骨细胞中上调（hsa-miR-483- 5 p），6种在正常软骨细胞中上调（hsa-miR-149*、hsa-miR-582- 3 p、hsa-miR-1227、hsa-miR-634、hsa-miR-576- 5 p和hsa-miR-641）。这些分析结果通过qPCR检测一些选定的miRNA得到验证。计算机模拟分析预测，在正常和OA软骨细胞中差异表达的miRNA可能改变的关键分子途径包括TGF-β、Wnt、Erb和mTOR信号传导;所有这些都涉及关节软骨的发育、维持和破坏。我们已经鉴定了7个在OA和正常软骨细胞中差异表达的miRNAs。我们潜在的miRNA靶点预测和差异表达的miRNA改变的信号级联支持检测到的miRNA在OA病理学中的潜在参与。由于miRNA在介导靶mRNA翻译成蛋白质中的重要性，鉴定这些在正常和OA软骨细胞微粒中差异表达的miRNA可能具有重要的诊断和治疗潜力。需要进一步的研究来了解这些miRNAs的功能，包括寻找它们的靶mRNA基因，这可能会导致OA治疗的新治疗策略的开发。
Osteoarthritis (OA) is a multifactorial disease characterized by destruction of the articular cartilage due to environmental, mechanical and genetic components. The genetics of OA is complex and is not completely understood. Recent works have demonstrated the importance of microRNAs (miRNAs) in cartilage function. MiRNAs are a class of small noncoding RNAs that regulate gene expression and are involved in different cellular process: apoptosis, proliferation, development, glucose and lipid metabolism. The aim of this study was to identify and characterize the expression profile of miRNAs in normal and OA chondrocytes and to determine their role in the OA. Chondrocytes were moved to aggregate culture and evaluated using histological and qPCR techniques. miRNAs were isolated and analyzed using the Agilent Human miRNA Microarray. Of the 723 miRNAs analyzed, 7 miRNAs showed a statistically significant differential expression. Amongst these 7 human miRNAs, 1 was up-regulated in OA chondrocytes (hsa-miR-483-5p) and 6 were up-regulated in normal chondrocytes (hsa-miR-149*, hsa-miR-582-3p, hsa-miR-1227, hsa-miR-634, hsa-miR-576-5p and hsa-miR-641). These profiling results were validated by the detection of some selected miRNAs by qPCR. In silico analyses predicted that key molecular pathways potentially altered by the miRNAs differentially expressed in normal and OA chondrocytes include TGF-beta, Wnt, Erb and mTOR signalling; all of them implicated in the development, maintenance and destruction of articular cartilage. We have identified 7 miRNAs differentially expressed in OA and normal chondrocytes. Our potential miRNA target predictions and the signalling cascades altered by the differentially expressed miRNAs supports the potential involvement of the detected miRNAs in OA pathology. Due to the importance of miRNA in mediating the translation of target mRNA into protein, the identification of these miRNAs differentially expressed in normal and OA chondrocyte micropellets could have important diagnostic and therapeutic potential. Further studies are needed to know the function of these miRNAs, including the search of their target mRNA genes, which could lead to the development of novel therapeutic strategies for the OA treatment.
登录
查看更多内容
影响因子：
14.9
作者：
Imbeaud S;Graudens E;Boulanger V;Barlet X;Zaborski P;Eveno E;Mueller O;Schroeder A;Auffray C
通讯作者：
Auffray C
影响因子：
14.9
作者：
Kozomara A;Griffiths-Jones S
通讯作者：
Griffiths-Jones S
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
影响因子：
--
作者：
Dunn, Walter;DuRaine, Grayson;Reddi, A. Hari
通讯作者：
Reddi, A. Hari