A Signature of CirculatingmiRNAsAssociated With Fibrous Dysplasia of Bone: themirDysStudy
A Signature of CirculatingmiRNAsAssociated With Fibrous Dysplasia of Bone: themirDysStudy
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DOI：
10.1002/jbmr.4111
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发表时间：
2020-07-21
影响因子：
6.2
通讯作者：
Chapurlat, Roland
中科院分区：
文献类型：
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作者：
Legrand, Melanie A.;Millet, Marjorie;Chapurlat, Roland
纤维结构不良（FD）是一种罕见的骨病，由编码Gs α蛋白的gnas激活突变引起，通过过度刺激腺苷酸环化酶增强环磷酸腺苷（cAMP）的产生，并损害成骨细胞分化。临床表现范围从无症状到严重残疾的多骨裂形式，解释了GNAS突变的马赛克分布。医生必须应对FD发病机制知识的空白，缺乏预后标志物和缺乏特异性治疗。鉴别FD的特异性生物标志物是改善临床和治疗方法的重要一步。由microRNAs （miRNAs）驱动的表观遗传调控，被称为骨病的有前途的生物标志物，可能参与FD。我们寻找FD患者与对照组相比表达差异的循环mirna，这些mirna反映了成骨相关基因和骨紊乱的失调。使用下一代测序技术对从20名患者（10名多骨和10名单骨）和10名对照中收集的患者血清进行全球miRNA分析。通过实时qPCR，我们从82名患者和82名对照者的血清中选择了19个miRNA用于miRNA验证阶段。在调整错误发现率（FDR）后，发现筛选鉴定出111个在患者血清中差异表达的mirna。在82例患者中，55%为多囊症，73%为女性，平均年龄42岁。6种mirna （miR-25-3p、miR-93-5p、miR-182-5p、miR-324-5p、miR-363-3p和miR-451a）在血清中显著过表达，伴有FDR
Fibrous dysplasia (FD) is a rare bone disease caused by activating mutations ofGNASencoding the Gs alpha protein, enhancing cyclic adenosine monophosphate (cAMP) production by overstimulation of adenylyl cyclase and impairing osteoblastic differentiation. The clinical presentation ranges from asymptomatic to polyostotic forms with severe disability, explained by the mosaic distribution of the GNAS mutation. Physicians have to deal with the gap of knowledge in FD pathogenesis, the absence of prognostic markers and the lack of specific treatment. The identification of specific biomarkers for FD is an important step to improve the clinical and therapeutic approaches. An epigenetic regulation driven by microRNAs (miRNAs), known as promising biomarkers in bone disease, could be involved in FD. We have sought circulating miRNAs that are differentially expressed in FD patients compared to controls and would reflect dysregulations of osteogenesis-related genes and bone disorder. The global miRNA profiling was performed using Next Generation Sequencing in patient serum collected from a discovery cohort of 20 patients (10 polyostotic and 10 monostotic) and 10 controls. From these, we selected 19 miRNAs for a miRNA validation phase from serum of 82 patients and 82 controls, using real-time qPCR. Discovery screening identified 111 miRNAs differentially expressed in patient serum, after adjusting for the false discovery rate (FDR). Among the 82 patients, 55% were polyostotic, and 73% were women with a mean age of 42 years. Six miRNAs (miR-25-3p, miR-93-5p, miR-182-5p, miR-324-5p, miR-363-3p, and miR-451a) were significantly overexpressed in serum, with FDR