@article{10902/13537,
year = {2017},
month = {3},
url = {http://hdl.handle.net/10902/13537},
abstract = {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 osteoblastexpressed 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.},
publisher = {Nature Publishing Group},
publisher = {Sci Rep 2017 Mar 31; 7(1): 516},
title = {SNPs in bone-related miRNAs are associated with the osteoporotic phenotype},
author = {Ugarte, Laura De and Caro Molina, Enrique and Rodríguez Sanz, Maria and García Pérez, Miguel Angel and Olmos Martínez, José Manuel and Sosa Henríquez, Manuel and Pérez Cano, Ramón and Gómez Alonso, Carlos and Rio, Luis
 Del and Mateo Agudo, Jesús and Blázquez Cabrera, José Antonio and González Macías, Jesús and Pino Montes, Javier del and Muñoz Torres, Manuel and Diaz Curiel, Manuel and Malouf, Jorge and Cano, Antonio and Pérez Castrillon, José Luis and Nogues, Xavier and Garcia Giralt, Natalia and Diez Perez, Adolfo},
}