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

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 osteopo...

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Detalhes bibliográficos
Autores: Ugarte Corbalán, Laura de, 1988-, Caro-Molina, Enrique, Rodríguez Sanz, Maria, 1984-, Nogués Solán, Xavier, Garcia Giralt, Natàlia, Díez Pérez, Adolfo
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/34050
Acesso em linha:http://hdl.handle.net/10230/34050
http://dx.doi.org/10.1038/s41598-017-00641-7
Access Level:acceso abierto
Palavra-chave:Fenotip
Ossos
Fractures
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spelling SNPs in bone-related miRNAs are associated with the osteoporotic phenotypeUgarte Corbalán, Laura de, 1988-Caro-Molina, EnriqueRodríguez Sanz, Maria, 1984-Nogués Solán, XavierGarcia Giralt, NatàliaDíez Pérez, AdolfoFenotipOssosFracturesBiogenesis 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 disordersNature Publishing Group201820182017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/34050http://dx.doi.org/10.1038/s41598-017-00641-7reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésScientific Reports. 2017 Mar 31;7(1):516Copyright © 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/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/340502026-06-12T07:21:37Z
dc.title.none.fl_str_mv SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
title SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
spellingShingle SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
Ugarte Corbalán, Laura de, 1988-
Fenotip
Ossos
Fractures
title_short SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
title_full SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
title_fullStr SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
title_full_unstemmed SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
title_sort SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
dc.creator.none.fl_str_mv Ugarte Corbalán, Laura de, 1988-
Caro-Molina, Enrique
Rodríguez Sanz, Maria, 1984-
Nogués Solán, Xavier
Garcia Giralt, Natàlia
Díez Pérez, Adolfo
author Ugarte Corbalán, Laura de, 1988-
author_facet Ugarte Corbalán, Laura de, 1988-
Caro-Molina, Enrique
Rodríguez Sanz, Maria, 1984-
Nogués Solán, Xavier
Garcia Giralt, Natàlia
Díez Pérez, Adolfo
author_role author
author2 Caro-Molina, Enrique
Rodríguez Sanz, Maria, 1984-
Nogués Solán, Xavier
Garcia Giralt, Natàlia
Díez Pérez, Adolfo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Fenotip
Ossos
Fractures
topic Fenotip
Ossos
Fractures
description 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
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/34050
http://dx.doi.org/10.1038/s41598-017-00641-7
url http://hdl.handle.net/10230/34050
http://dx.doi.org/10.1038/s41598-017-00641-7
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Scientific Reports. 2017 Mar 31;7(1):516
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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