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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. IMPACT STATEMENT: This is the first study in which hsa-miR-708-5p has been identified in peripheral blood monocytes (osteoclast precursors) and associated with postmenopausal osteoporosis through small RNA-Sequencing, in an Admixed Mexican Mestizo population. By conducting in silico and bioinformatic analyzes, we identified target genes and important signaling pathways involved in bone metabolism pointing hsa-miR-708-5p as a candidate marker for osteoporosis in Mexican population. These approaches provide a landscape of the post-transcriptional regulation, which can be useful for the management of postmenopausal osteoporosis along with the potential use of microRNAs as markers for its early detection.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with oxidative stress and characterized by chronic inflammation. Kidney malfunction, an aggressive characteristic of this disease, is not present in all affected individuals. The Nrf2-Keap1 pathway is important in protecting against oxidative stress and inflammation. Mouse models and genome-wide scans have suggested NRF2 (Nuclear factor (erythroid-derived 2)-like 2) as a candidate gene for susceptibility to SLE. We therefore investigated whether NRF2 polymorphisms are associated with childhood-onset SLE in a Mexican Mestizo population. Two single nucleotide polymorphisms (SNPs) were genotyped by TaqMan® assays in 362 patients with childhood-onset SLE and 379 controls. We found no significant association between susceptibility to SLE and NRF2 polymorphisms. However, after population stratification by gender, the heterozygous genotype of the -653G/A SNP was significantly associated with nephritis in females only [OR = 1.81, CI (1.04—3.12), p = 0.032]. This association was stronger in females affected with severe nephritis [classes IV—VI; OR = 2.16, CI (1.12—4.15), p = 0.019]. Our results suggest that NRF2 is not associated with susceptibility to childhood-onset SLE, but it could confer a risk for developing kidney malfunction in SLE-affected individuals.