Cheng Vincent Ka-Fai, Au Philip Chun-Ming, Tan Kathryn Cb, Cheung Ching-Lung
Department of Pharmacology and Pharmacy The University of Hong Kong Pokfulam Hong Kong.
Department of Medicine The University of Hong Kong Pokfulam Hong Kong.
JBMR Plus. 2018 Nov 5;3(1):2-13. doi: 10.1002/jbm4.10115. eCollection 2019 Jan.
The small non-coding microRNAs (miRNAs) are post-transcription regulators that modulate diverse cellular process in bone cells. Because optimal miRNA targeting is essential for their function, single-nucleotide polymorphisms (SNPs) within or proximal to the loci of miRNA (miR-SNPs) or mRNA (PolymiRTS) could potentially disrupt the miRNA-mRNA interaction, leading to changes in bone metabolism and osteoporosis. Recent human studies of skeletal traits using miRNA profiling, genomewide association studies, and functional studies started to decipher the complex miRNA regulatory network. These studies have indicated that miRNAs may be a promising bone marker. This review focuses on human miRNA studies on bone traits and discusses how genetic variants affect bone metabolic pathways. Major ex vivo investigations using human samples supported with animal and in vitro models have shed light on the mechanistic role of miRNAs. Furthermore, studying the miRNAs' signatures in secondary osteoporosis and osteoporotic medications such as teriparatide (TPTD) and denosumab (DMab) have provided valuable insight into clinical management of the disease. © 2018 The Authors. Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
小型非编码微小RNA(miRNA)是转录后调节因子,可调节骨细胞中的多种细胞过程。由于最佳的miRNA靶向对于其功能至关重要,因此miRNA(miR-SNP)或mRNA(PolymiRTS)基因座内或附近的单核苷酸多态性(SNP)可能会破坏miRNA与mRNA的相互作用,从而导致骨代谢和骨质疏松症的变化。最近利用miRNA谱分析、全基因组关联研究和功能研究对骨骼性状进行的人体研究开始解读复杂的miRNA调控网络。这些研究表明,miRNA可能是一种很有前景的骨标志物。本综述重点关注关于骨性状的人体miRNA研究,并讨论基因变异如何影响骨代谢途径。使用人体样本并辅以动物和体外模型进行的主要离体研究揭示了miRNA的作用机制。此外,研究继发性骨质疏松症和骨质疏松症药物(如特立帕肽(TPTD)和地诺单抗(DMab))中的miRNA特征,为该疾病的临床管理提供了有价值的见解。© 2018作者。由Wiley Periodicals, Inc.代表美国骨与矿物质研究学会出版。