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

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dc.contributor.author Ugarte Corbalán, Laura de, 1988-
dc.contributor.author Yoskovitz, Guy
dc.contributor.author Balcells, Susana
dc.contributor.author Güerri Fernández, Roberto
dc.contributor.author Martinez-Diaz, Santos
dc.contributor.author Mellibovsky, Leonardo
dc.contributor.author Urreizti, Roser
dc.contributor.author Nogués Solan, Francesc Xavier
dc.contributor.author Grinberg, Daniel
dc.contributor.author Garcia Giralt, Natàlia
dc.contributor.author Díez Pérez, Adolfo
dc.date.accessioned 2016-02-10T09:55:36Z
dc.date.available 2016-02-10T09:55:36Z
dc.date.issued 2015
dc.identifier.citation Ugarte L de, Yoskovitz G, Balcells S, Güerri-Fernández R, Martinez-Diaz S, Mellibovsky L. et al. MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones. BMC Med Genomics. 2015 Nov 10;8:75. doi: 10.1186/s12920-015-0149-2.
dc.identifier.issn 1755-8794
dc.identifier.uri http://hdl.handle.net/10230/25763
dc.description.abstract 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.
dc.description.sponsorship 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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.rights This 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.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Osteoporosi
dc.subject.other Regulació genètica
dc.subject.other Fractures
dc.title MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones.
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/s12920-015-0149-2
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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