MiR-422a as a Potential Cellular MicroRNA Biomarker for Postmenopausal Osteoporosis

Abstract

BackgroundMicroRNAs (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 FindingsWe 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/SignificanceOur study suggests that miR-422a in human circulating monocytes (osteoclast precursors) is a potential miRNA biomarker underlying postmenopausal osteoporosis.

Evaluation of MicroRNA 125b as a potential biomarker for postmenopausal osteoporosis

“…The aforestated study was one of its first kinds in identifying miR-133a as a biomarker in circulating monocytes. The same group identified another miRNA in circulating monocytes, miR-422a, as a potential biomarker for postmenopausal osteoporosis [13]. More recently, 5 dysregulated miRNAs in osteosarcoma were identified in microarray analysis and upon further subjection to pathway analysis only miR-194-5p was enriched in osteoporosis related pathways suggesting miR-194-5p as a potential biomarker for postmenopausal osteoporosis [11].…”

“…A most recent study identified a range of dysregulated miRNAs in osteoporosis related pathways and suggests miR-194-5p as a viable biomarker for postmenopausal osteoporosis [11]. Similarly, miR133a and miR422a have been identified as potential biomarkers for postmenopausal osteoporosis [12,13]. The present study aims to expand the repertoire of dysregulated miRNAs in postmenopausal osteoporosis and identify other potential miRNA biomarkers for early detection of postmenopausal osteoporosis.…”

Analysis of the Bone MicroRNome in Osteoporotic Fractures

“…A number of investigators have used in vitro culture systems and animal models trying to elucidate the role of some miRNAs in the regulation of bone cell activity [6,10,[21][22][23][24][25][26][27][28][29]. However, only scarce data are available about the involvement of miRNAs in common human skeletal disorders, such as osteoporosis and osteoarthritis.…”

The role of MicroRNAs in Osteoclasts and Osteoporosis

“…This group also demonstrated an apparent negative correlation between each of these 5 genes and miR-422a, although none of the correlations reached statistical significance. 80 These studies suggest that miR-422a is possibly involved in the regulation of postmenopausal osteoporosis and might be a potential biomarker of osteoporosis.…”