61509 20190709135534.0 doi 10.1038/s41598-017-00641-7 sideral 98475 ART-2017-98475 eng De-Ugarte, L. SNPs in bone-related miRNAs are associated with the osteoporotic phenotype 2017 Access copy available to the general public Unrestricted Biogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we measured these BMD-associated microRNAs in trabecular bone from osteoporotic hip fractures comparing to non-osteoporotic bone by qPCR. Both microRNAs were found overexpressed in fractured bone. Increased matrix mineralization was observed after miR-3679-3p inhibition in human osteoblastic cells. Finally, genotypes of rs6430498 and rs12512664 were correlated with expression levels of miR-3679 and miR-4274, respectively, in osteoblasts. In both cases, the allele that generated higher microRNA expression levels was associated with lower BMD values. In conclusion, two osteoblast-expressed microRNAs, miR-3679 and miR-4274, were associated with BMD; their overexpression could contribute to the osteoporotic phenotype. These findings open new areas for the study of bone disorders. info:eu-repo/grantAgreement/ES/ISCIII/RD12-0043-0022 info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI13-00116 info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-02775 info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-02582 info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI10-01537 info:eu-repo/grantAgreement/ES/ISCIII/CB16-10-00245 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.122 2017 MULTIDISCIPLINARY SCIENCES 12 / 64 = 0.188 2017 Q1 T1 1.533 2017 Multidisciplinary 2017 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Caro-Molina, E. Rodríguez-Sanz, M. Garciá-Pérez, M. A. Olmos, J. M. Sosa-Henríquez, M. Pérez-Cano, R. Gómez-Alonso, C. Del Rio, L. (orcid)0000-0001-7516-4737 Mateo-Agudo, J. Universidad de Zaragoza Blázquez-Cabrera, J. A. González-Maciás, J. Pino-Montes, J. Munõz-Torres, M. DIaz-Curiel, M. Malouf, J. Cano, A. Pérez-Castrillon, J. L. Nogues, X. Garcia-Giralt, N. DIez-Perez, A. 1004 830 Universidad de Zaragoza Dpto. Cirugía,Ginecol.Obstetr. Área Traumatología y Ortopedia 7 (2017), 516 [10 pp.] Sci. rep. Scientific reports 2045-2322 1657353 http://zaguan.unizar.es/record/61509/files/texto_completo.pdf Versión publicada 113787 http://zaguan.unizar.es/record/61509/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:61509 articulos driver 2019-07-09-12:03:44 ARTICLE