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

Laura De-Ugarte, Enrique Caro-Molina, Maria Rodríguez-Sanz, Miguel Angel Garciá-Pérez, José M. Olmos, Manuel Sosa-Henríquez, Ramón Pérez-Cano, Carlos Gómez-Alonso, Luis Del Rio, Jesús Mateo-Agudo, José Antonio Blázquez-Cabrera, Jesús González-Maciás, Javier Del Pino-Montes, Manuel Munõz-Torres, Manuel DIaz-Curiel, Jorge Malouf, Antonio Cano, José Luis Pérez-Castrillon, Xavier Nogues, Natalia Garcia-GiraltAdolfo DIez-Perez

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10 Citations (Scopus)

Abstract

© 2017 The Author(s). 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.
Original languageEnglish
Article number516
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

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