Emerging roles for long noncoding RNAs in skeletal biology and disease.
Emerging roles for long noncoding RNAs in skeletal biology and disease.
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DOI：
10.1080/03008207.2016.1194406
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发表时间：
2017-01
影响因子：
2.9
通讯作者：
McAlinden A
中科院分区：
文献类型：
--
作者：
Huynh NP;Anderson BA;Guilak F;McAlinden A
正常的骨骼发育需要转录网络、信号通路和生物力学信号的紧密协调，而这些通路中的许多在影响软骨和骨骼的病理条件下是失调的。最近，长非编码RNA(IncRNAs)在细胞表型的形成和维持中起着重要的作用，测序技术的进步已经导致在不同类型的细胞中识别出数千个IncRNAs，包括软骨和骨中的细胞。很明显，IncRNAs在基因表达调控中起着关键作用。例如，它们可以通过染色质调节在细胞核中发挥表观遗传调节的作用，以控制基因转录；或者在细胞质中，它们可以作为蛋白质结合伙伴的支架，或者调节其他编码和非编码RNA的活动。在这篇综述中，我们讨论了越来越多的IncRNAs参与骨骼系统的正常发育和/或动态平衡，这些IncRNAs可能发挥作用的潜在机制，以及在体外和体内研究IncRNA功能的方法的最新进展。最后，我们讨论了IncRNAs作为骨骼系统疾病的生物标记物和治疗靶点的可能用途，包括骨关节炎、骨质疏松症和骨骼系统癌症。
Normal skeletal development requires tight coordination of transcriptional networks, signaling pathways, and biomechanical cues, and many of these pathways are dysregulated in pathological conditions affecting cartilage and bone. Recently, a significant role has been identified for long noncoding RNAs (IncRNAs) in developing and maintaining cellular phenotypes, and improvements in sequencing technologies have led to the identification of thousands of IncRNAs across diverse cell types, including the cells within cartilage and bone. It is clear that IncRNAs play critical roles in regulating gene expression. For example, they can function as epigenetic regulators in the nucleus via chromatin modulation to control gene transcription, or in the cytoplasm, where they can function as scaffolds for protein-binding partners or modulate the activity of other coding and noncoding RNAs. In this review, we discuss the growing list of IncRNAs involved in normal development and/or homeostasis of the skeletal system, the potential mechanisms by which these IncRNAs might function, and recent improvements in the methodologies available to study IncRNA functions in vitro and in vivo. Finally, we address the likely utility of IncRNAs as biomarkers and therapeutic targets for diseases of the skeletal system, including osteoarthritis, osteoporosis, and in cancers of the skeletal system.