TY - JOUR
T1 - SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
AU - De-Ugarte, Laura
AU - Caro-Molina, Enrique
AU - Rodríguez-Sanz, Maria
AU - Garciá-Pérez, Miguel Angel
AU - Olmos, José M.
AU - Sosa-Henríquez, Manuel
AU - Pérez-Cano, Ramón
AU - Gómez-Alonso, Carlos
AU - Del Rio, Luis
AU - Mateo-Agudo, Jesús
AU - Blázquez-Cabrera, José Antonio
AU - González-Maciás, Jesús
AU - Pino-Montes, Javier Del
AU - Munõz-Torres, Manuel
AU - DIaz-Curiel, Manuel
AU - Malouf, Jorge
AU - Cano, Antonio
AU - Pérez-Castrillon, José Luis
AU - Nogues, Xavier
AU - Garcia-Giralt, Natalia
AU - DIez-Perez, Adolfo
PY - 2017/12/1
Y1 - 2017/12/1
N2 - © 2017 The Author(s). 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.
AB - © 2017 The Author(s). 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.
U2 - 10.1038/s41598-017-00641-7
DO - 10.1038/s41598-017-00641-7
M3 - Article
SN - 2045-2322
VL - 7
JO - SCIENTIFIC REPORTS
JF - SCIENTIFIC REPORTS
IS - 1
M1 - 516
ER -