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 miR...

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Authors: De-Ugarte, Laura, Yoskovitz, Guy, Balcells Comas, Susana, Güerri-Fernández, Robert, Martínez-Díaz, Santos, Mellibovsky, Leonardo, Urreizti, Roser, Nogués Solán, Xavier, Grinberg Vaisman, Daniel Raúl, Garcia Giralt, Natàlia, Díez Pérez, Adolfo
Format: article
Status:Published version
Publication Date:2015
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/67857
Online Access:https://hdl.handle.net/2445/67857
Access Level:Open access
Keyword:Osteoporosi
Epigènesi
Ossos
RNA
Fractures
Osteoporosis
Epigenesis
Bones
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spelling MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bonesDe-Ugarte, LauraYoskovitz, GuyBalcells Comas, SusanaGüerri-Fernández, RobertMartínez-Díaz, SantosMellibovsky, LeonardoUrreizti, RoserNogués Solán, XavierGrinberg Vaisman, Daniel RaúlGarcia Giralt, NatàliaDíez Pérez, AdolfoOsteoporosiEpigènesiOssosRNAFracturesOsteoporosisEpigenesisBonesRNAFracturesBackground 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.BioMed Central2015201520152015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion11 p.application/pdfhttps://hdl.handle.net/2445/67857Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.1186/s12920-015-0149-2BMC Medical Genomics, 2015, vol. 8:75, p. 1-11http://dx.doi.org/10.1186/s12920-015-0149-2cc-by (c) De-Ugarte, Laura et al., 2015http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/678572026-05-29T05:05:01Z
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
De-Ugarte, Laura
Osteoporosi
Epigènesi
Ossos
RNA
Fractures
Osteoporosis
Epigenesis
Bones
RNA
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 De-Ugarte, Laura
Yoskovitz, Guy
Balcells Comas, Susana
Güerri-Fernández, Robert
Martínez-Díaz, Santos
Mellibovsky, Leonardo
Urreizti, Roser
Nogués Solán, Xavier
Grinberg Vaisman, Daniel Raúl
Garcia Giralt, Natàlia
Díez Pérez, Adolfo
author De-Ugarte, Laura
author_facet De-Ugarte, Laura
Yoskovitz, Guy
Balcells Comas, Susana
Güerri-Fernández, Robert
Martínez-Díaz, Santos
Mellibovsky, Leonardo
Urreizti, Roser
Nogués Solán, Xavier
Grinberg Vaisman, Daniel Raúl
Garcia Giralt, Natàlia
Díez Pérez, Adolfo
author_role author
author2 Yoskovitz, Guy
Balcells Comas, Susana
Güerri-Fernández, Robert
Martínez-Díaz, Santos
Mellibovsky, Leonardo
Urreizti, Roser
Nogués Solán, Xavier
Grinberg Vaisman, Daniel Raúl
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
Epigènesi
Ossos
RNA
Fractures
Osteoporosis
Epigenesis
Bones
RNA
Fractures
topic Osteoporosi
Epigènesi
Ossos
RNA
Fractures
Osteoporosis
Epigenesis
Bones
RNA
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
2015
2015
2015
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 https://hdl.handle.net/2445/67857
url https://hdl.handle.net/2445/67857
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: http://dx.doi.org/10.1186/s12920-015-0149-2
BMC Medical Genomics, 2015, vol. 8:75, p. 1-11
http://dx.doi.org/10.1186/s12920-015-0149-2
dc.rights.none.fl_str_mv cc-by (c) De-Ugarte, Laura et al., 2015
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) De-Ugarte, Laura et al., 2015
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11 p.
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Genètica, Microbiologia i Estadística)
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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score 15,198674

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