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

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dc.contributor.author Ugarte Corbalán, Laura de, 1988-
dc.contributor.author Caro-Molina, Enrique
dc.contributor.author Rodríguez Sanz, Maria, 1984-
dc.contributor.author Nogués Solan, Francesc Xavier
dc.contributor.author Garcia Giralt, Natàlia
dc.contributor.author Díez Pérez, Adolfo
dc.date.accessioned 2018-03-06T08:11:17Z
dc.date.available 2018-03-06T08:11:17Z
dc.date.issued 2017
dc.identifier.citation De-Ugarte L, Caro-Molina E, Rodríguez-Sanz M, García-Pérez MA, Olmos JM, Sosa-Henríquez M. et al. SNPs in bone-related miRNAs are associated with the osteoporotic phenotype. Sci Rep. 2017 Mar 31;7(1):516. DOI: 10.1038/s41598-017-00641-7
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10230/34050
dc.description.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 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
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Publishing Group
dc.relation.ispartof Scientific Reports. 2017 Mar 31;7(1):516
dc.rights Copyright © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
dc.subject.other Fenotip
dc.subject.other Ossos
dc.subject.other Fractures
dc.title SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41598-017-00641-7
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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