OstemiR: a novel panel of microRNA biomarkers in osteoblastic and osteocytic differentiation from mesencymal stem cells.
OstemiR: a novel panel of microRNA biomarkers in osteoblastic and osteocytic differentiation from mesencymal stem cells.
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DOI：
10.1371/journal.pone.0058796
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Calderwood SK
中科院分区：
文献类型：
--
作者：
Eguchi T;Watanabe K;Hara ES;Ono M;Kuboki T;Calderwood SK
MicroRNA（miRNAs）是一种由21-25个核苷酸组成的小分子RNA，通过抑制mRNA向蛋白质的翻译、促进mRNA降解和控制基因转录来调节细胞行为。在这项研究中，我们研究了细胞培养物的miRNA表达的签名进行成骨细胞和成骨细胞分化的间充质干细胞（MSC）使用小鼠MSC线KUSA-A1和人MSC。在KUSA-A1细胞成骨/骨细胞分化过程中，利用miRNA PCR阵列定量90种类型的miRNA。与成骨细胞和成骨细胞标志物的mRNA诱导相一致的是，包括miR-30家族、let-7家族、miR-21、miR-16、miR-155、miR-322和Snord 85在内的几十种miRNA的表达水平在分化过程中发生了变化。这些miRNAs被预测识别成骨分化、干细胞、上皮细胞和细胞周期相关的mRNA，因此被命名为OstemiR。在这些OstemiR中，根据成骨过程中的表达模式以及成熟的miRNA结构，将miR-30家族分为miR-30 b/c和miR-30 a/d/e组。在稳定的miR-30 d转染子中的计算机模拟预测和随后的qRT-PCR阐明了miR-30 d对已知的骨形成调节因子的上下文依赖性靶向，包括骨桥蛋白/spp 1、lifr、ccn 2/ctgf、ccn 1/cn 61、runx 2、sox 9以及新的关键因子，包括lin 28 a、hnrnpa 3、hspa 5/grp 78、eed和pcgf 5。此外，在hMSC成骨细胞分化中，敲低人OstemiR-541增加了骨桥蛋白/SPP 1表达和钙化，表明miR-541是成骨细胞分化的负调节因子。这些观察结果表明OstemiR，特别是miR-541和miR-30家族在骨生成中对新靶点的阶段特异性作用。
MicroRNAs (miRNAs) are small RNA molecules of 21–25 nucleotides that regulate cell behavior through inhibition of translation from mRNA to protein, promotion of mRNA degradation and control of gene transcription. In this study, we investigated the miRNA expression signatures of cell cultures undergoing osteoblastic and osteocytic differentiation from mesenchymal stem cells (MSC) using mouse MSC line KUSA-A1 and human MSCs. Ninety types of miRNA were quantified during osteoblastic/osteocytic differentiation in KUSA-A1 cells utilizing miRNA PCR arrays. Coincidently with mRNA induction of the osteoblastic and osteocytic markers, the expression levels of several dozen miRNAs including miR-30 family, let-7 family, miR-21, miR-16, miR-155, miR-322 and Snord85 were changed during the differentiation process. These miRNAs were predicted to recognize osteogenic differentiation-, stemness-, epinegetics-, and cell cycle-related mRNAs, and were thus designated OstemiR. Among those OstemiR, the miR-30 family was classified into miR-30b/c and miR-30a/d/e groups on the basis of expression patterns during osteogenesis as well as mature miRNA structures. In silico prediction and subsequent qRT-PCR in stable miR-30d transfectants clarified that context-dependent targeting of miR-30d on known regulators of bone formation including osteopontin/spp1, lifr, ccn2/ctgf, ccn1/cyr61, runx2, sox9 as well as novel key factors including lin28a, hnrnpa3, hspa5/grp78, eed and pcgf5. In addition, knockdown of human OstemiR miR-541 increased Osteopontin/SPP1 expression and calcification in hMSC osteoblastic differentiation, indicating that miR-541 is a negative regulator of osteoblastic differentiation. These observations indicate stage-specific roles of OstemiR especially miR-541 and the miR-30 family on novel targets in osteogenesis.
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64.8
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64.8
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影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
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