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首页> 外文期刊>Journal of cellular physiology. >Differentially expressed miRNAs in bone after methotrexate treatment
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Differentially expressed miRNAs in bone after methotrexate treatment

机译：差异表达microrna在骨头甲氨蝶呤治疗

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摘要

Previous studies have shown that administration of antimetabolite methotrexate (MTX) caused a reduced trabecular bone volume and increased marrow adiposity (bone/fat switch), for which the underlying molecular mechanisms and recovery potential are unclear. Altered expression of microRNAs (miRNAs) has been shown to be associated with dysregulation of osteogenic and/or adipogenic differentiation by disrupting target gene expression. First, the current study confirmed the bone/fat switch following MTX treatment in precursor cell culture models in vitro. Then, using a rat intensive 5-once daily MTX treatment model, this study aimed to identify miRNAs associated with bone damage and recovery (in a time course over Days 3, 6, 9, and 14 after the first MTX treatment). RNA isolated from bone samples of treated and control rats were subjected to miRNA array and reverse transcription-polymerase chain reaction validation, which identified five upregulated miRNA candidates, namely, miR-155-5p, miR-154-5p, miR-344g, miR-6215, and miR-6315. Target genes of these miRNAs were predicted using TargetScan and miRDB. Then, the protein-protein network was established via STRING database, after which the miRNA-key messenger RNA (mRNA) network was constructed by Cytoscape. Functional annotation and pathway enrichment analyses for miR-6315 were performed by DAVID database. We found that TGF-β signaling was the most significantly enriched pathway and subsequent dual-luciferase assays suggested that Smad2 was the direct target of miR-6315. Our current study showed that miR-6315 might be a vital regulator involved in bone and marrow fat formation. Also, this study constructed a comprehensive miRNA-mRNA regulatory network, which may contribute to the pathogenesis/prognosis of MTX-associated bone loss and bone marrow adiposity.
机译：先前的研究已经表明,管理抗代谢物氨甲蝶呤(MTX)引起减少骨小梁体积和增加骨髓脂肪过多(骨/脂肪开关),的潜在的分子机制和恢复潜在的尚不清楚。小分子核糖核酸(microrna)已被证明是与成骨的失调有关破坏和/或脂肪形成的分化目标基因的表达。以下简称MTX证实骨/脂肪开关治疗在前驱细胞培养模型体外。MTX治疗模型,本研究旨在识别microrna与骨破坏和恢复(在一个时间超过3天,6,9日和14第一个MTX治疗)。治疗和控制老鼠的样本受到microrna的数组和反向聚合酶链反应验证,确定了五个调节microrna的候选人,即mir - 155 - 5 - p, mir - 154 - 5 - p,mir - 344 g, mir - 6215和mir - 6315。这些microrna是使用TargetScan和预测miRDB。建立数据库,通过字符串之后miRNA-key信使核糖核酸(mRNA)网络由Cytoscape。和通路富集分析mir - 6315由大卫数据库。信号是最重要的途径和随后dual-luciferase化验建议Smad2的直接目标mir - 6315。可能是一个至关重要的监管机构参与骨骼和骨髓脂肪形成。构建了一个综合miRNA-mRNA监管网络,这可能导致的发病机理/预后MTX-associated骨头损失和骨髓脂肪过多。

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