Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/67857
Title: MiRNA profiling of whole trabecular bone: identification of osteoporosis-related changes in MiRNAs in human hip bones
Author: De-Ugarte, Laura
Yoskovitz, Guy
Balcells Comas, Susana
Güerri-Fernández, Robert
Martínez-Díaz, Santos
Mellibovsky, Leonardo
Urreizti Frexedas, Roser.
Nogués, Xavier
Grinberg Vaisman, Daniel Raúl
García-Giralt, Natalia
Diez Pérez, Adolfo
Keywords: Osteoporosi
Epigènesi
Ossos
RNA
Fractures
Osteoporosis
Epigenesis
Bones
RNA
Fractures
Issue Date: 10-Nov-2015
Publisher: BioMed Central
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.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1186/s12920-015-0149-2
It is part of: BMC Medical Genomics, 2015, vol. 8:75, p. 1-11
Related resource: http://dx.doi.org/10.1186/s12920-015-0149-2
URI: http://hdl.handle.net/2445/67857
ISSN: 1755-8794
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)

Files in This Item:
File Description SizeFormat 
655347.pdf963.83 kBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons