SNPs in bone-related miRNAs are associated with the osteoporotic phenotype

De-Ugarte, L. ; 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. ; 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.

Resumen: 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.

Idioma: Inglés

DOI: 10.1038/s41598-017-00641-7

Año: 2017

Publicado en: Scientific reports 7 (2017), 516 [10 pp.]
ISSN: 2045-2322

Factor impacto JCR: 4.122 (2017)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 12 / 64 = 0.188 (2017) - Q1 - T1

Factor impacto SCIMAGO: 1.533 - Multidisciplinary (Q1)

Financiación: info:eu-repo/grantAgreement/ES/ISCIII/CB16-10-00245
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI10-01537
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-02582
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-02775
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI13-00116
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/RD12-0043-0022

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Traumatología y Ortopedia (Dpto. Cirugía,Ginecol.Obstetr.)