MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones.

BACKGROUND: MicroRNAs (miRNAs) are important regulators of gene expression, with documented roles in bone metabolism and osteoporosis, suggesting potential therapeutic targets. Our aim was to identify miRNAs differentially expressed in fractured vs nonfractured bones. Additionally, we performed a mi...

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Autores: Ugarte Corbalán, Laura de, 1988-, Yoskovitz, Guy, Balcells, Susana, Güerri Fernández, Roberto, Martinez-Diaz, Santos, Mellibovsky, Leonardo, Urreizti, Roser, Nogués Solán, Xavier, Grinberg, Daniel, Garcia Giralt, Natàlia, Díez Pérez, Adolfo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/25763
Acceso en línea:http://hdl.handle.net/10230/25763
http://dx.doi.org/10.1186/s12920-015-0149-2
Access Level:acceso abierto
Palabra clave:Osteoporosi
Regulació genètica
Fractures
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network_name_str España
repository_id_str
dc.title.none.fl_str_mv MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones.
title MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones.
spellingShingle MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones.
Ugarte Corbalán, Laura de, 1988-
Osteoporosi
Regulació genètica
Fractures
title_short MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones.
title_full MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones.
title_fullStr MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones.
title_full_unstemmed MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones.
title_sort MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones.
dc.creator.none.fl_str_mv Ugarte Corbalán, Laura de, 1988-
Yoskovitz, Guy
Balcells, Susana
Güerri Fernández, Roberto
Martinez-Diaz, Santos
Mellibovsky, Leonardo
Urreizti, Roser
Nogués Solán, Xavier
Grinberg, Daniel
Garcia Giralt, Natàlia
Díez Pérez, Adolfo
author Ugarte Corbalán, Laura de, 1988-
author_facet Ugarte Corbalán, Laura de, 1988-
Yoskovitz, Guy
Balcells, Susana
Güerri Fernández, Roberto
Martinez-Diaz, Santos
Mellibovsky, Leonardo
Urreizti, Roser
Nogués Solán, Xavier
Grinberg, Daniel
Garcia Giralt, Natàlia
Díez Pérez, Adolfo
author_role author
author2 Yoskovitz, Guy
Balcells, Susana
Güerri Fernández, Roberto
Martinez-Diaz, Santos
Mellibovsky, Leonardo
Urreizti, Roser
Nogués Solán, Xavier
Grinberg, Daniel
Garcia Giralt, Natàlia
Díez Pérez, Adolfo
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Osteoporosi
Regulació genètica
Fractures
topic Osteoporosi
Regulació genètica
Fractures
description BACKGROUND: MicroRNAs (miRNAs) are important regulators of gene expression, with documented roles in bone metabolism and osteoporosis, suggesting potential therapeutic targets. Our aim was to identify miRNAs differentially expressed in fractured vs nonfractured bones. Additionally, we performed a miRNA profiling of primary osteoblasts to assess the origin of these differentially expressed miRNAs. METHODS: Total RNA was extracted from (a) fresh femoral neck trabecular bone from women undergoing hip replacement due to either osteoporotic fracture (OP group, n = 6) or osteoarthritis in the absence of osteoporosis (Control group, n = 6), matching the two groups by age and body mass index, and (b) primary osteoblasts obtained from knee replacement due to osteoarthritis (n = 4). Samples were hybridized to a microRNA array containing more than 1900 miRNAs. Principal component analysis (PCA) plots and heat map hierarchical clustering were performed. For comparison of expression levels, the threshold was set at log fold change > 1.5 and a p-value < 0.05 (corrected for multiple testing). RESULTS: Both PCA and heat map analyses showed that the samples clustered according to the presence or absence of fracture. Overall, 790 and 315 different miRNAs were detected in fresh bone samples and in primary osteoblasts, respectively, 293 of which were common to both groups. A subset of 82 miRNAs was differentially expressed (p < 0.05) between osteoporotic and control osteoarthritic samples. The eight miRNAs with the lowest p-values (and for which a validated miRNA qPCR assay was available) were assayed, and two were confirmed: miR-320a and miR-483-5p. Both were over-expressed in the osteoporotic samples and expressed in primary osteoblasts. miR-320a is known to target CTNNB1 and predicted to regulate RUNX2 and LEPR, while miR-483-5p down-regulates IGF2. We observed a reduction trend for this target gene in the osteoporotic bone. CONCLUSIONS: We identified two osteoblast miRNAs over-expressed in osteoporotic fractures, which opens novel prospects for research and therapy.
publishDate 2015
dc.date.none.fl_str_mv 2015
2016
2016
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/10230/25763
http://dx.doi.org/10.1186/s12920-015-0149-2
url http://hdl.handle.net/10230/25763
http://dx.doi.org/10.1186/s12920-015-0149-2
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv BMC Medical Genomics. 2015 Nov 10;8:75
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones.Ugarte Corbalán, Laura de, 1988-Yoskovitz, GuyBalcells, SusanaGüerri Fernández, RobertoMartinez-Diaz, SantosMellibovsky, LeonardoUrreizti, RoserNogués Solán, XavierGrinberg, DanielGarcia Giralt, NatàliaDíez Pérez, AdolfoOsteoporosiRegulació genèticaFracturesBACKGROUND: MicroRNAs (miRNAs) are important regulators of gene expression, with documented roles in bone metabolism and osteoporosis, suggesting potential therapeutic targets. Our aim was to identify miRNAs differentially expressed in fractured vs nonfractured bones. Additionally, we performed a miRNA profiling of primary osteoblasts to assess the origin of these differentially expressed miRNAs. METHODS: Total RNA was extracted from (a) fresh femoral neck trabecular bone from women undergoing hip replacement due to either osteoporotic fracture (OP group, n = 6) or osteoarthritis in the absence of osteoporosis (Control group, n = 6), matching the two groups by age and body mass index, and (b) primary osteoblasts obtained from knee replacement due to osteoarthritis (n = 4). Samples were hybridized to a microRNA array containing more than 1900 miRNAs. Principal component analysis (PCA) plots and heat map hierarchical clustering were performed. For comparison of expression levels, the threshold was set at log fold change > 1.5 and a p-value < 0.05 (corrected for multiple testing). RESULTS: Both PCA and heat map analyses showed that the samples clustered according to the presence or absence of fracture. Overall, 790 and 315 different miRNAs were detected in fresh bone samples and in primary osteoblasts, respectively, 293 of which were common to both groups. A subset of 82 miRNAs was differentially expressed (p < 0.05) between osteoporotic and control osteoarthritic samples. The eight miRNAs with the lowest p-values (and for which a validated miRNA qPCR assay was available) were assayed, and two were confirmed: miR-320a and miR-483-5p. Both were over-expressed in the osteoporotic samples and expressed in primary osteoblasts. miR-320a is known to target CTNNB1 and predicted to regulate RUNX2 and LEPR, while miR-483-5p down-regulates IGF2. We observed a reduction trend for this target gene in the osteoporotic bone. CONCLUSIONS: We identified two osteoblast miRNAs over-expressed in osteoporotic fractures, which opens novel prospects for research and therapy.This work was supported by grant FIS PI10/01537 and the Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF) (Carlos III Health Institute, Science and Innovation Ministry), and FEDER funds. Grant SAF2011-25431 and PIB2010AR-00473 (Science and Innovation Ministry), and the support from the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER, an initiative of ISCIII) are also acknowledged. Grants from the Generalitat de Catalunya (DIUE; 2009 SGR 818, 2009 SGR 971) also supported this work.BioMed Central201620162015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/25763http://dx.doi.org/10.1186/s12920-015-0149-2reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésBMC Medical Genomics. 2015 Nov 10;8:75This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://​creativecommons.​org/​licenses/​by/​4.​0/​), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/257632026-05-29T05:05:01Z
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