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

Abstract: 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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Sci Rep 2017 Mar 31; 7(1): 516

Editorial: Nature Publishing Group

 Fecha de publicación: 01/03/2017

Nº de páginas: 10

Tipo de publicación: Artículo de Revista

 DOI: 10.1038/s41598-017-00641-7

ISSN: 2045-2322

Url de la publicación: http://dx.doi.org/10.1038/s41598-017-00641-7

Autores/as

UGARTE, LAURA DE

CARO MOLINA, ENRIQUE

RODRÍGUEZ SANZ, MARIA

GARCÍA PÉREZ, MIGUEL ANGEL

SOSA HENRÍQUEZ, MANUEL

PÉREZ CANO, RAMÓN

GÓMEZ ALONSO, CARLOS

RIO, LUIS DEL

MATEO AGUDO, JESÚS

BLÁZQUEZ CABRERA, JOSÉ ANTONIO

PINO MONTES, JAVIER DEL

MUÑOZ TORRES, MANUEL

DIAZ CURIEL, MANUEL

MALOUF, JORGE

CANO, ANTONIO

PÉREZ CASTRILLON, JOSÉ LUIS

NOGUES, XAVIER

GARCIA GIRALT, NATALIA

DIEZ PEREZ, ADOLFO