Cao Zheng, Moore Benjamin T, Wang Yang, Peng Xian-Hao, Lappe Joan M, Recker Robert R, Xiao Peng
Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, PR China; Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, Nebraska, United States of America.
Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, Nebraska, United States of America.
PLoS One. 2014 May 12;9(5):e97098. doi: 10.1371/journal.pone.0097098. eCollection 2014.
MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that regulate gene expression by targeting mRNAs. Recently, miRNAs have been shown to play important roles in the etiology of various diseases. However, little is known about their roles in the development of osteoporosis. Circulating monocytes are osteoclast precursors that also produce various factors important for osteoclastogenesis. Previously, we have identified a potential biomarker miR-133a in circulating monocytes for postmenopausal osteoporosis. In this study, we aimed to further identify significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis.
METHODOLOGY/PRINCIPAL FINDINGS: We used ABI TaqMan miRNA array followed by qRT-PCR validation in human circulating monocytes from 10 high BMD and 10 low BMD postmenopausal Caucasian women to identify miRNA biomarkers. MiR-422a was up-regulated with marginal significance (P = 0.065) in the low compared with the high BMD group in the array analysis. However, a significant up-regulation of miR-422a was identified in the low BMD group by qRT-PCR analysis (P = 0.029). We also performed bioinformatic target gene analysis and found several potential target genes of miR-422a which are involved in osteoclastogenesis. Further qRT-PCR analyses of the target genes in the same study subjects showed that the expression of five of these genes (CBL, CD226, IGF1, PAG1, and TOB2) correlated negatively with miR-422a expression.
CONCLUSIONS/SIGNIFICANCE: Our study suggests that miR-422a in human circulating monocytes (osteoclast precursors) is a potential miRNA biomarker underlying postmenopausal osteoporosis.
微小RNA（miRNA）是一类短链非编码RNA分子，通过靶向mRNA来调节基因表达。最近，miRNA已被证明在多种疾病的病因学中发挥重要作用。然而，它们在骨质疏松症发展中的作用却知之甚少。循环单核细胞是破骨细胞前体，也产生对破骨细胞生成重要的各种因子。此前，我们已在循环单核细胞中鉴定出一种用于绝经后骨质疏松症的潜在生物标志物miR-133a。在本研究中，我们旨在进一步鉴定绝经后骨质疏松症患者循环单核细胞中重要的miRNA生物标志物。
方法/主要发现：我们使用ABI TaqMan miRNA芯片，随后在10名高骨密度和10名低骨密度的绝经后白种女性的循环单核细胞中进行qRT-PCR验证，以鉴定miRNA生物标志物。在芯片分析中，与高骨密度组相比，低骨密度组中miR-422a上调具有边缘显著性（P = 0.065）。然而，通过qRT-PCR分析在低骨密度组中鉴定出miR-422a显著上调（P = 0.029）。我们还进行了生物信息学靶基因分析，发现了几个参与破骨细胞生成的miR-422a潜在靶基因。对同一研究对象中靶基因的进一步qRT-PCR分析表明，其中五个基因（CBL、CD226、IGF1、PAG1和TOB2）的表达与miR-422a表达呈负相关。
结论/意义：我们的研究表明，人类循环单核细胞（破骨细胞前体）中的miR-422a是绝经后骨质疏松症潜在的miRNA生物标志物。
