Hu Hai, He Xiaodi, Zhang Yazhong, Wu Rongrong, Chen Jiajia, Lin Yuxin, Shen Bairong
Center for Systems Biology, Soochow University, Suzhou, China.
Department of Orthopedics, Huainan First People's Hospital of Anhui Province, Huainan, China.
Front Genet. 2020 Mar 3;11:181. doi: 10.3389/fgene.2020.00181. eCollection 2020.
Osteoporosis (OP) is a systemic bone disease with a series of clinical symptoms. The use of screening biomarkers in OP management is therefore of clinical significance, especially in the era of precision medicine and intelligent healthcare. MicroRNAs (miRNAs) are small, non-coding RNAs with the potential to regulate gene expression at the post-transcriptional level. Accumulating evidence indicates that miRNAs may serve as biomarkers for OP prediction and prevention. However, few studies have emphasized the role of miRNAs in systems-level pathogenesis during OP development. In this article, literature-reported OP miRNAs were manually collected and analyzed based on a systems biology paradigm. Functional enrichment studies were performed to decode the underlying mechanisms of miRNAs in OP etiology and therapeutics in three-dimensional space, i.e., integrated miRNA-gene-pathway analysis. In particular, interactions between miRNAs and three well-known OP pathways, i.e., estrogen-endocrine, WNT/β-catenin signaling, and RANKL/RANK/OPG, were systematically investigated, and the effects of non-genetic factors on personalized OP prevention and therapy were discussed. This article is a comprehensive review of OP miRNAs, and bridges the gap between an understanding of OP pathogenesis and clinical translation.
骨质疏松症（OP）是一种具有一系列临床症状的全身性骨病。因此，在OP管理中使用筛查生物标志物具有临床意义，尤其是在精准医学和智能医疗时代。微小RNA（miRNA）是一类小的非编码RNA，具有在转录后水平调节基因表达的潜力。越来越多的证据表明，miRNA可能作为OP预测和预防的生物标志物。然而，很少有研究强调miRNA在OP发生发展过程中系统水平发病机制中的作用。在本文中，基于系统生物学范式手动收集并分析了文献报道的OP相关miRNA。进行了功能富集研究，以在三维空间中解码miRNA在OP病因学和治疗学中的潜在机制，即整合miRNA-基因-通路分析。特别地，系统研究了miRNA与三个著名的OP通路（即雌激素-内分泌、WNT/β-连环蛋白信号传导和RANKL/RANK/OPG）之间的相互作用，并讨论了非遗传因素对个性化OP预防和治疗的影响。本文是对OP相关miRNA的全面综述，弥合了对OP发病机制的理解与临床转化之间的差距。
