Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis.
Identification of suitable reference gene and biomarkers of serum miRNAs for osteoporosis.
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骨质疏松症血清 miRNA 的合适参考基因和生物标志物的鉴定
DOI：
10.1038/srep36347
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发表时间：
2016-11-08
影响因子：
4.6
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Chen J;Li K;Pang Q;Yang C;Zhang H;Wu F;Cao H;Liu H;Wan Y;Xia W;Wang J;Dai Z;Li Y
我们的目的是通过一项系统的研究，在血清miRNA中寻找合适的标准化参考基因，并筛选潜在的诊断骨质疏松的新的生物标志物。采用机械性卸载和雌激素缺乏两种骨质疏松模型。通过基因芯片的大规模筛选、qPCR验证和统计算法，我们首次确定miR-25-3p是两种类型骨质疏松的合适参考基因，并且在成骨细胞和破骨细胞的分化过程中也表现出稳定性。然后通过基因芯片和定量聚合酶链式反应验证，筛选出15个在去卵巢大鼠血清中差异表达的miRNA。我们进一步在绝经后妇女和卧床恒河猴中检测了这15个miRNAs，并通过ROC分析评价了它们的诊断价值。在这些miRNAs中，miR-30b-5p在骨量减少或骨质疏松的绝经后妇女中显著下调，miR-103-3p、miR-142-3p、miR-328-3p仅在骨质疏松中显著下调。均与BMD呈正相关。恒河猴长期卧床后，除miR328-3p外，其余3种miRNAs均呈下降趋势。他们的AUC值(ALL>；0.75)证明了诊断的潜力。我们的结果提供了一个可靠的标准化参考基因，并验证了一组循环中的miRNAs作为检测绝经后和机械卸载后骨质疏松的非侵入性生物标志物。
Our objective was to identify suitable reference genes in serum miRNA for normalization and screen potential new biomarkers for osteoporosis diagnosis by a systematic study. Two types of osteoporosis models were used like as mechanical unloading and estrogen deficiency. Through a large-scale screening using microarray, qPCR validation and statistical algorithms, we first identified miR-25-3p as a suitable reference gene for both type of osteoporosis, which also showed stability during the differentiation processes of osteoblast and osteoclast. Then 15 serum miRNAs with differential expression in OVX rats were identified by microarray and qPCR validation. We further detected these 15 miRNAs in postmenopausal women and bedrest rhesus monkeys and evaluated their diagnostic value by ROC analysis. Among these miRNAs, miR-30b-5p was significantly down-regulated in postmenopausal women with osteopenia or osteoporosis; miR-103-3p, miR-142-3p, miR-328-3p were only significantly decreased in osteoporosis. They all showed positive correlations with BMD. Except miR328-3p, the other three miRNAs were also declined in the rhesus monkeys after long-duration bedrest. Their AUC values (all >0.75) proved the diagnostic potential. Our results provided a reliable normalization reference gene and verified a group of circulating miRNAs as non-invasive biomarkers in the detection of postmenopausal- and mechanical unloading- osteoporosis.
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影响因子：
3.7
作者：
Eguchi T;Watanabe K;Hara ES;Ono M;Kuboki T;Calderwood SK
通讯作者：
Calderwood SK
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通讯作者：
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作者：
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通讯作者：
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