Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, Nebraska, United States of America.
PLoS One. 2012;7(4):e34641. doi: 10.1371/journal.pone.0034641. Epub 2012 Apr 10.
Osteoporosis mainly occurs in postmenopausal women, which is characterized by low bone mineral density (BMD) due to unbalanced bone resorption by osteoclasts and formation by osteoblasts. Circulating monocytes play important roles in osteoclastogenesis by acting as osteoclast precursors and secreting osteoclastogenic factors, such as IL-1, IL-6 and TNF-α. MicroRNAs (miRNAs) have been implicated as important biomarkers in various diseases. The present study aimed to find 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 circulating monocytes to identify miRNA biomarkers in 10 high and 10 low BMD postmenopausal Caucasian women. MiR-133a was upregulated (P=0.007) in the low compared with the high BMD groups in the array analyses, which was also validated by qRT-PCR (P=0.044). We performed bioinformatic target gene analysis and found three potential osteoclast-related target genes, CXCL11, CXCR3 and SLC39A1. In addition, we performed Pearson correlation analyses between the expression levels of miR-133a and the three potential target genes in the 20 postmenopausal women. We did find negative correlations between miR-133a and all the three genes though not significant.
CONCLUSIONS/SIGNIFICANCE: This is the first in vivo miRNA expression analysis in human circulating monocytes to identify novel miRNA biomarkers underlying postmenopausal osteoporosis. Our results suggest that miR-133a in circulating monocytes is a potential biomarker for postmenopausal osteoporosis.
骨质疏松症主要发生在绝经后妇女中,其特征是由于破骨细胞吸收骨和成骨细胞形成骨之间的不平衡导致骨矿物质密度(BMD)降低。循环单核细胞通过作为破骨细胞前体和分泌破骨细胞生成因子(如 IL-1、IL-6 和 TNF-α)在破骨细胞生成中起重要作用。微小 RNA(miRNA)已被认为是各种疾病的重要生物标志物。本研究旨在寻找人类循环单核细胞中与绝经后骨质疏松症相关的显著 miRNA 生物标志物。
方法/主要发现:我们使用 ABI TaqMan® miRNA 阵列,然后通过 qRT-PCR 验证循环单核细胞中的 miRNA 生物标志物,以鉴定 10 名高 BMD 和 10 名低 BMD 绝经后白种女性中的 miRNA 生物标志物。在阵列分析中,miR-133a 在低 BMD 组中上调(P=0.007),qRT-PCR 验证也得到了验证(P=0.044)。我们进行了生物信息学靶基因分析,发现了三个潜在的破骨细胞相关靶基因,CXCL11、CXCR3 和 SLC39A1。此外,我们还对 20 名绝经后妇女的 miR-133a 和三个潜在靶基因的表达水平进行了 Pearson 相关分析。我们确实发现 miR-133a 与所有三个基因之间存在负相关,但没有统计学意义。
结论/意义:这是首次在人类循环单核细胞中进行体内 miRNA 表达分析,以确定绝经后骨质疏松症的新 miRNA 生物标志物。我们的结果表明,循环单核细胞中的 miR-133a 是绝经后骨质疏松症的潜在生物标志物。