Five Freely Circulating miRNAs and Bone Tissue miRNAs Are Associated With Osteoporotic Fractures
Five Freely Circulating miRNAs and Bone Tissue miRNAs Are Associated With Osteoporotic Fractures
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DOI：
10.1002/jbmr.2175
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发表时间：
2014-08-01
影响因子：
6.2
通讯作者：
van Griensven, Martijn
中科院分区：
文献类型：
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作者：
Seeliger, Claudine;Karpinski, Katrin;van Griensven, Martijn
骨质疏松症是一种全身性骨骼疾病，其特征是骨脆性增加和骨折风险增加。根据世界卫生组织，骨质疏松症是10种最常见的疾病之一，影响欧洲，美国和日本约7500万人。在这种情况下，识别特定的microRNA（miRNA）签名是新的诊断和治疗方法的重要一步。随着新的出版物鉴定出与各种类型癌症相关的游离循环细胞外miRNA，人们对miRNA作为生物标志物的兴趣集中在了一起。本研究的目的是确定与非骨化性骨折患者相比，骨化性骨折患者的特异性miRNA。为了进行阵列分析，从20名髋部骨折患者的血清中分离miRNA，转录，并将样品合并为10份骨化性和10份非骨化性标本。对于每个样本池，进行人血清和血浆miRNA PCR阵列，其能够鉴定83种不同的miRNA。随后，对发现在阵列中受到调节的每种miRNA进行单独的验证分析，然后是从30名阿尔茨海默病患者和30名非阿尔茨海默病患者的血清中分离的miRNA样品和从20名阿尔茨海默病患者和20名非阿尔茨海默病患者的骨组织中分离的miRNA样品。通过对受调控的miRNAs的验证分析，我们鉴定了9种miRNAs，即miR-21、miR-23 a、miR-24、miR-93、miR-100、miR-122 a、miR-124 a、miR-125 b和miR-148 a，它们在骨质疏松患者血清中显著上调。在骨质疏松患者的骨组织中，我们发现miR-21、miR-23 a、miR-24、miR-25、miR-100和miR-125 b显示出显著更高的表达。共有5种miRNA在血清和骨组织中均显示上调。这项研究揭示了几种miRNAs在骨质疏松患者中的重要作用，并表明它们可用作诊断目的的生物标志物，并可能成为治疗骨质疏松患者骨丢失和优化骨折愈合的靶点。(C)2014年美国骨与矿物质研究学会。
Osteoporosis as a systemic skeletal disorder is characterized by increased bone fragility and the risk of fractures. According to the World Health Organization, osteoporosis is one of the 10 most common diseases and affects approximately 75 million people in Europe, the United States, and Japan. In this context, the identification of specific microRNA (miRNA) signatures is an important step for new diagnostic and therapeutic approaches. The focus of interest on miRNAs as biomarkers came with new publications identifying free circulating extracellular miRNAs associated with various types of cancer. This study aimed to identify specific miRNAs in patients with osteoporotic fractures compared with nonosteoporotic fractures. For the array analysis, miRNAs were isolated from the serum of 20 patients with hip fractures, transcribed, and the samples were pooled into 10 osteoporotic and 10 nonosteoporotic specimens. With each pool of samples, human serum and plasma miRNA PCR arrays were performed, which are able to identify 83 different miRNAs. Subsequently, a separate validation analysis of each miRNA found to be regulated in the array followed with miRNA samples isolated from the serum of 30 osteoporotic and 30 nonosteoporotic patients and miRNA samples isolated from the bone tissue of 20 osteoporotic and 20 nonosteoporotic patients. With the validation analysis of the regulated miRNAs, we identified 9 miRNAs, namely miR-21, miR-23a, miR-24, miR-93, miR-100, miR-122a, miR-124a, miR-125b, and miR-148a, that were significantly upregulated in the serum of patients with osteoporosis. In the bone tissue of osteoporotic patients, we identified that miR-21, miR-23a, miR-24, miR-25, miR-100, and miR-125b displayed a significantly higher expression. A total of 5 miRNAs display an upregulation both in serum and bone tissue. This study reveals an important role for several miRNAs in osteoporotic patients and suggested that they may be used as biomarkers for diagnostic purposes and may be a target for treating bone loss and optimizing fracture healing in osteoporotic patients. (C) 2014 American Society for Bone and Mineral Research.