Circulating microRNAs as potential diagnostic biomarkers for osteoporosis.

Circulating microRNAs as potential diagnostic biomarkers for osteoporosis.
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DOI:
10.1038/s41598-018-26525-y
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发表时间:
2018-05-30
期刊:
影响因子:
4.6
通讯作者:
Barraclough DL
Barraclough DL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mandourah AY;Ranganath L;Barraclough R;Vinjamuri S;Hof RV;Hamill S;Czanner G;Dera AA;Wang D;Barraclough DL

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骨质疏松症是世界范围内最常见的年龄相关性骨骼疾病,通常在首次骨折发生前无临床症状。microRNA是骨重建过程中的关键分子调节剂,并在血液中稳定。本项目的目的是使用先进的PCR阵列初步鉴定与骨质疏松症相关的循环microRNA,并使用RT-qPCR在临床样本中验证所鉴定的差异表达microRNA。共招募了161名受试者,139名受试者在招募前获得当地伦理批准后被纳入本研究。从所有血清和血浆样品中提取、纯化、定量和分析RNA。最初使用miRNA PCR阵列鉴定差异表达的miRNA,并使用RT-qPCR在139份血清和134份血浆临床样品中进行验证。在使用RT-qPCR验证个体临床样品中鉴定的miRNA后,循环miRNA、hsa-miR-122- 5 p和hsa-miR-4516在非骨质疏松对照、骨质疏松症和骨质疏松症患者之间统计学显著差异表达。进一步分析表明,这些microRNA的水平与骨质疏松患者脆性骨折和低骨密度相关。结果表明,循环hsa-miR-122- 5 p和hsa-miR-4516可能是未来骨质疏松症的潜在诊断生物标志物。
Osteoporosis is the most common age-related bone disease worldwide and is usually clinically asymptomatic until the first fracture happens. MicroRNAs are critical molecular regulators in bone remodelling processes and are stabilised in the blood. The aim of this project was to identify circulatory microRNAs associated with osteoporosis using advanced PCR arrays initially and the identified differentially-expressed microRNAs were validated in clinical samples using RT-qPCR. A total of 161 participants were recruited and 139 participants were included in this study with local ethical approvals prior to recruitment. RNAs were extracted, purified, quantified and analysed from all serum and plasma samples. Differentially-expressed miRNAs were identified using miRNA PCR arrays initially and validated in 139 serum and 134 plasma clinical samples using RT-qPCR. Following validation of identified miRNAs in individual clinical samples using RT-qPCR, circulating miRNAs, hsa-miR-122-5p and hsa-miR-4516 were statistically significantly differentially-expressed between non-osteoporotic controls, osteopaenia and osteoporosis patients. Further analysis showed that the levels of these microRNAs were associated with fragility fracture and correlated with the low bone mineral density in osteoporosis patients. The results show that circulating hsa-miR-122-5p and hsa-miR-4516 could be potential diagnostic biomarkers for osteoporosis in the future.
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