Identification of miR-708-5p in peripheral blood monocytes: Potential marker for postmenopausal osteoporosis in Mexican-Mestizo population

Abstract

Osteoporosis is the most frequent disorder of bone metabolism, owing to an alteration between osteoclast and osteoblast activity, which results from the interaction of genetic, environmental, and epigenetic factors. microRNAs, small non-coding RNAs of around 22 nucleotides with important regulatory roles in gene regulation, that target mRNAs for post-transcriptional destabilization have been suggested as biomarkers in several disorders. In this work, we used small RNA sequencing to identify microRNAs from peripheral blood monocytes that were differentially expressed between non-osteoporotic and osteoporotic Mexican postmenopausal women, to elucidate the potential role of microRNAs as non-invasive marker candidates in osteoporosis. We identified six candidate microRNAs: four were up-regulated (miR-708-5p, miR-34b-5p, miR-3161, miR-328-5p), while two were down-regulated (miR-4422 and miR-939-3p) in osteoporotic women. Differential expression was validated by quantitative RT-PCR and only the upregulation of miR-708-5p was found to be statistically significant. Bioinformatic analysis of target genes for miR-708-5p showed 15 signaling pathways related to bone metabolism. Since monocytes are osteoclast precursors, 10 potential target genes present in these pathways and related to osteoclastogenesis were identified (AKT1, AKT2, CCND1, PARP1, SMAD3, CXCL5, FKBP5, MAP2K3, MMP2, and IKBKG). Five of them were found to be down-regulated according to microarray expression data. This is the first time that miR-708-5p has been identified in peripheral blood monocytes and associated with postmenopausal osteoporosis. Our results suggest that miR-708-5p reduces the expression of AKT1, AKT2, PARP1 FKBP5, and MP2K3 in peripheral blood monocytes contributing to an osteoporotic phenotype and could be a candidate marker for postmenopausal osteoporosis in Mexican population.