SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
EstadísticasView Usage Statistics
Full recordShow full item record
AuthorUgarte, Laura De; Caro Molina, Enrique; Rodríguez Sanz, Maria; García Pérez, Miguel Angel; Olmos Martínez, José Manuel; Sosa Henríquez, Manuel; Pérez Cano, Ramón; Gómez Alonso, Carlos; Rio, Luis Del; Mateo Agudo, Jesús; Blázquez Cabrera, José Antonio; González Macías, Jesús; Pino Montes, Javier del; Muñoz Torres, Manuel; Diaz Curiel, Manuel; Malouf, Jorge; Cano, Antonio; Pérez Castrillon, José Luis; Nogues, Xavier; [et al.]
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 osteoblastexpressed 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.