RT Journal Article
T1 SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
A1 De-Ugarte, Laura
A1 Caro-Molina, Enrique
A1 Rodríguez-Sanz, Maria
A1 García-Pérez, Miguel Angel
A1 Olmos, José M
A1 Sosa-Henríquez, Manuel
A1 Pérez-Cano, Ramón
A1 Gómez-Alonso, Carlos
A1 Del Rio, Luis
A1 Mateo-Agudo, Jesús
A1 Blázquez-Cabrera, José Antonio
A1 González-Macías, Jesús
A1 Del Pino-Montes, Javier
A1 Muñoz-Torres, Manuel
A1 Diaz-Curiel, Manuel
A1 Malouf, Jorge
A1 Cano, Antonio
A1 Pérez-Castrillon, José Luis
A1 Nogues, Xavier
A1 Garcia-Giralt, Natalia
A1 Diez-Perez, Adolfo
K1 Alelos
K1 Densidad ósea
K1 Enfermedades óseas
K1 Cuello femoral
K1 Fracturas de cadera
K1 Genotipo
K1 Humanos
K1 MicroARNs
K1 Osteoblastos
K1 Fracturas osteoporóticas
K1 Fenotipo
K1 Polimorfismo de nucleótido simple
AB Biogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we measured these BMD-associated microRNAs in trabecular bone from osteoporotic hip fractures comparing to non-osteoporotic bone by qPCR. Both microRNAs were found overexpressed in fractured bone. Increased matrix mineralization was observed after miR-3679-3p inhibition in human osteoblastic cells. Finally, genotypes of rs6430498 and rs12512664 were correlated with expression levels of miR-3679 and miR-4274, respectively, in osteoblasts. In both cases, the allele that generated higher microRNA expression levels was associated with lower BMD values. In conclusion, two osteoblast-expressed microRNAs, miR-3679 and miR-4274, were associated with BMD; their overexpression could contribute to the osteoporotic phenotype. These findings open new areas for the study of bone disorders.
PB Nature Publishing Group
YR 2017
FD 2017-03-31
LK http://hdl.handle.net/10668/2644
UL http://hdl.handle.net/10668/2644
LA en
NO De-Ugarte L, Caro-Molina E, Rodríguez-Sanz M, García-Pérez MA, Olmos JM, Sosa-Henríquez M et al.SNPs in bone-related miRNAs are associated with the osteoporotic phenotype. Sci Rep. 2017 Mar 31;7(1):516.
DS RISalud
RD Apr 6, 2025