Circulating microRNAs as novel biomarkers for bone diseases - Complex signatures for multifactorial diseases?

Circulating microRNAs as novel biomarkers for bone diseases - Complex signatures for multifactorial diseases?
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DOI:
10.1016/j.mce.2015.10.015
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发表时间:
2016-09-05
影响因子:
4.1
通讯作者:
Grillari, Johannes
Grillari, Johannes
中科院分区:
医学2区
文献类型:
--
作者:
Hackl, Matthias;Heilmeier, Ursula;Grillari, Johannes

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生物标志物是临床研究和实践中必不可少的工具。有用的生物标志物必须结合联合收割机良好的可测量性,与生物过程或结果的有效关联,并且如果用于临床实践,则应支持临床决策。在骨疾病的背景下,已经报道了几种类型的经验证的生物标志物。然而,由于这些生物标志物面临某些限制,因此对鉴定骨疾病的新生物标志物感兴趣,特别是与导致骨风险增加的疾病病理学紧密相关的那些。microRNA(miRNAs)是无细胞血液中发现的最丰富的RNA种类。微囊泡内封装或结合到蛋白质,循环miRNA是非常稳定的分析物,可以使用黄金标准技术,如定量聚合酶链反应(qPCR)进行测量。然而,循环miRNA的分析面临着几个预分析以及分析挑战。从生物学的角度来看,越来越多的证据表明miRNAs在包括骨稳态在内的各种生物学过程的调节中发挥重要作用。此外,miRNA转录水平或miRNA分泌水平的特定变化与某些骨疾病的发生和进展有关。直到最近,才报道了在骨质减少、骨质疏松和脆性骨折患者中进行循环miRNA分析的结果。通过将这些发现与细胞衰老和老化或肌肉生理学和肌肉减少症中循环miRNA的研究进行比较,观察到一些重叠。这表明在骨质疏松症期间观察到的特征可能不是骨中病理生理学的特异性,而是整合了来自几种组织类型的信息。尽管有这些有希望的第一批数据,但仍有更多的工作要做,直到循环miRNA可以在临床研究,临床常规和个性化医疗中作为骨骼疾病的既定和强大的诊断工具。(C)2015年,作者。出版社:Elsevier爱尔兰Ltd.
Biomarkers are essential tools in clinical research and practice. Useful biomarkers must combine good measurability, validated association with biological processes or outcomes, and should support clinical decision making if used in clinical practice. Several types of validated biomarkers have been reported in the context of bone diseases. However, because these biomarkers face certain limitations there is an interest in the identification of novel biomarkers for bone diseases, specifically in those that are tightly linked to the disease pathology leading to increased fracture-risk. MicroRNAs (miRNAs) are the most abundant RNA species to be found in cell-free blood. Encapsulated within microvesicles or bound to proteins, circulating miRNAs are remarkably stable analytes that can be measured using gold-standard technologies such as quantitative polymerase-chain-reaction (qPCR). Nevertheless, the analysis of circulating miRNAs faces several pre-analytical as well as analytical challenges. From a biological view, there is accumulating evidence that miRNAs play essential roles in the regulation of various biological processes including bone homeostasis. Moreover, specific changes in miRNA transcription levels or miRNA secretory levels have been linked to the development and progression of certain bone diseases. Only recently, results from circulating miRNAs analysis in patients with osteopenia, osteoporosis and fragility fractures have been reported. By comparing these findings to studies on circulating miRNAs in cellular senescence and aging or muscle physiology and sarcopenia, several overlaps were observed. This suggests that signatures observed during osteoporosis might not be specific to the pathophysiology in bone, but rather integrate information from several tissue types. Despite these promising first data, more work remains to be done until circulating miRNAs can serve as established and robust diagnostic tools for bone diseases in clinical research, clinical routine and in personalized medicine. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.