SNPs in bone-related miRNAs are associated with the osteoporotic phenotype

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 osteopo...

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Detalles Bibliográficos
Autores: De-Ugarte, Laura, Caro-Molina, Enrique, Rodríguez-Sanz, Maria, García-Pérez, Miguel Angel, Olmos, José M., Sosa-Henríquez, Manuel, Pérez-Cano, Ramón, Gómez-Alonso, Carlos|||0000-0003-1424-8659, Del Rio, Luis|||0000-0003-0720-0673, Mateo-Agudo, Jesús, Blázquez-Cabrera, José Antonio, González-Macías, Jesús, Pino-Montes, Javier del, Muñoz-Torres, Manuel, Diaz-Curiel, Manuel|||0000-0002-7762-9398, Malouf Sierra, Jorge|||0000-0001-5185-520X, Cano, Antonio, Pérez-Castrillon, José Luis, Nogués Solán, Xavier|||0000-0002-5537-1859, Garcia-Giralt, Natalia|||0000-0001-6507-0147, Díez Pérez, Adolfo|||0000-0001-8162-0209
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:253850
Acceso en línea:https://ddd.uab.cat/record/253850
https://dx.doi.org/urn:doi:10.1038/s41598-017-00641-7
Access Level:acceso abierto
Descripción
Sumario: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.

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