MiRNA profiling of whole trabecular bone : identification of osteoporosis-related changes in MiRNAs in human hip bones
De-Ugarte, Laura (Institut Hospital del Mar d'Investigacions Mèdiques)
Yoskovitz, Guy (Institut Hospital del Mar d'Investigacions Mèdiques)
Balcells, Susana (Universitat de Barcelona. Departament de Genètica)
Güerri-Fernández, Robert (Hospital del Mar (Barcelona, Catalunya))
Martinez-Diaz, Santos (Hospital del Mar (Barcelona, Catalunya))
Mellibovsky, Leonardo (Hospital del Mar (Barcelona, Catalunya))
Urreizti, Roser (Universitat de Barcelona. Departament de Genètica)
Nogués Solán, Xavier (Hospital del Mar (Barcelona, Catalunya))
Grinberg, Daniel (Universitat de Barcelona. Departament de Genètica)
Garcia-Giralt, Natalia (Institut Hospital del Mar d'Investigacions Mèdiques)
Díez Pérez, Adolfo (Hospital del Mar (Barcelona, Catalunya))
Universitat Autònoma de Barcelona

Data:	2015
Resum:	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. 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). 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. We identified two osteoblast miRNAs over-expressed in osteoporotic fractures, which opens novel prospects for research and therapy. The online version of this article (doi:10. 1186/s12920-015-0149-2) contains supplementary material, which is available to authorized users.
Ajuts:	Instituto de Salud Carlos III PI10/01537 Ministerio de Economía y Competitividad SAF2011-25431 Ministerio de Economía y Competitividad PIB2010AR-00473 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-818 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-971
Drets:	Aquest 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.
Llengua:	Anglès
Document:	Article ; Versió publicada
Matèria:	Osteoporosis ; Micrornas ; Osteoblast ; Fracture ; Epigenetic regulation
Publicat a:	BMC medical genomics, Vol. 8 (november 2015) , ISSN 1755-8794

DOI: 10.1186/s12920-015-0149-2
PMID: 26555194

11 p, 963.8 KB

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