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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Autores: De-Ugarte, Laura, Caro-Molina, Enrique, Rodríguez-Sanz, Maria, García-Pérez, Miguel Angel, Olmos, José M., Sosa-Henríquez, Manuel, Pérez-Cano, Ramón, Gómez-Alonso, Carlos|||0000-0003-1424-8659, Del Rio, Luis|||0000-0003-0720-0673, Mateo-Agudo, Jesús, Blázquez-Cabrera, José Antonio, González-Macías, Jesús, Pino-Montes, Javier del, Muñoz-Torres, Manuel, Diaz-Curiel, Manuel|||0000-0002-7762-9398, Malouf Sierra, Jorge|||0000-0001-5185-520X, Cano, Antonio, Pérez-Castrillon, José Luis, Nogués Solán, Xavier|||0000-0002-5537-1859, Garcia-Giralt, Natalia|||0000-0001-6507-0147, Díez Pérez, Adolfo|||0000-0001-8162-0209
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:253850
Acceso en línea:https://ddd.uab.cat/record/253850
https://dx.doi.org/urn:doi:10.1038/s41598-017-00641-7
Access Level:acceso abierto
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spelling SNPs in bone-related miRNAs are associated with the osteoporotic phenotypeDe-Ugarte, LauraCaro-Molina, EnriqueRodríguez-Sanz, MariaGarcía-Pérez, Miguel AngelOlmos, José M.Sosa-Henríquez, ManuelPérez-Cano, RamónGómez-Alonso, Carlos|||0000-0003-1424-8659Del Rio, Luis|||0000-0003-0720-0673Mateo-Agudo, JesúsBlázquez-Cabrera, José AntonioGonzález-Macías, JesúsPino-Montes, Javier delMuñoz-Torres, ManuelDiaz-Curiel, Manuel|||0000-0002-7762-9398Malouf Sierra, Jorge|||0000-0001-5185-520XCano, AntonioPérez-Castrillon, José LuisNogués Solán, Xavier|||0000-0002-5537-1859Garcia-Giralt, Natalia|||0000-0001-6507-0147Díez Pérez, Adolfo|||0000-0001-8162-0209Biogenesis 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.Universitat Autònoma de Barcelona 22017-01-0120172017-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/253850https://dx.doi.org/urn:doi:10.1038/s41598-017-00641-7reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD12/0043/0022Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CB16/10/00245Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI10/01537Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/02775Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/02582Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/00116Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-775open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2538502026-06-06T12:50:31Z
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
De-Ugarte, Laura
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 De-Ugarte, Laura
Caro-Molina, Enrique
Rodríguez-Sanz, Maria
García-Pérez, Miguel Angel
Olmos, José M.
Sosa-Henríquez, Manuel
Pérez-Cano, Ramón
Gómez-Alonso, Carlos|||0000-0003-1424-8659
Del Rio, Luis|||0000-0003-0720-0673
Mateo-Agudo, Jesús
Blázquez-Cabrera, José Antonio
González-Macías, Jesús
Pino-Montes, Javier del
Muñoz-Torres, Manuel
Diaz-Curiel, Manuel|||0000-0002-7762-9398
Malouf Sierra, Jorge|||0000-0001-5185-520X
Cano, Antonio
Pérez-Castrillon, José Luis
Nogués Solán, Xavier|||0000-0002-5537-1859
Garcia-Giralt, Natalia|||0000-0001-6507-0147
Díez Pérez, Adolfo|||0000-0001-8162-0209
author De-Ugarte, Laura
author_facet De-Ugarte, Laura
Caro-Molina, Enrique
Rodríguez-Sanz, Maria
García-Pérez, Miguel Angel
Olmos, José M.
Sosa-Henríquez, Manuel
Pérez-Cano, Ramón
Gómez-Alonso, Carlos|||0000-0003-1424-8659
Del Rio, Luis|||0000-0003-0720-0673
Mateo-Agudo, Jesús
Blázquez-Cabrera, José Antonio
González-Macías, Jesús
Pino-Montes, Javier del
Muñoz-Torres, Manuel
Diaz-Curiel, Manuel|||0000-0002-7762-9398
Malouf Sierra, Jorge|||0000-0001-5185-520X
Cano, Antonio
Pérez-Castrillon, José Luis
Nogués Solán, Xavier|||0000-0002-5537-1859
Garcia-Giralt, Natalia|||0000-0001-6507-0147
Díez Pérez, Adolfo|||0000-0001-8162-0209
author_role author
author2 Caro-Molina, Enrique
Rodríguez-Sanz, Maria
García-Pérez, Miguel Angel
Olmos, José M.
Sosa-Henríquez, Manuel
Pérez-Cano, Ramón
Gómez-Alonso, Carlos|||0000-0003-1424-8659
Del Rio, Luis|||0000-0003-0720-0673
Mateo-Agudo, Jesús
Blázquez-Cabrera, José Antonio
González-Macías, Jesús
Pino-Montes, Javier del
Muñoz-Torres, Manuel
Diaz-Curiel, Manuel|||0000-0002-7762-9398
Malouf Sierra, Jorge|||0000-0001-5185-520X
Cano, Antonio
Pérez-Castrillon, José Luis
Nogués Solán, Xavier|||0000-0002-5537-1859
Garcia-Giralt, Natalia|||0000-0001-6507-0147
Díez Pérez, Adolfo|||0000-0001-8162-0209
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
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 2
2017-01-01
2017
2017-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/253850
https://dx.doi.org/urn:doi:10.1038/s41598-017-00641-7
url https://ddd.uab.cat/record/253850
https://dx.doi.org/urn:doi:10.1038/s41598-017-00641-7
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 RD12/0043/0022
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CB16/10/00245
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI10/01537
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/02775
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI12/02582
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI13/00116
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-775
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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