Title:
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SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
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Author:
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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; Del Rio, Luis; Mateo-Agudo, Jesús; Blázquez-Cabrera, José Antonio; González-Macías, Jesús; Pino-Montes, Javier del; Muñoz-Torres, Manuel; Diaz-Curiel, Manuel; Malouf Sierra, Jorge; Cano, Antonio; Pérez-Castrillon, José Luis; Nogués Solán, Xavier; Garcia-Giralt, Natalia; Díez Pérez, Adolfo; Universitat Autònoma de Barcelona
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Abstract:
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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. |
Rights:
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open access
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https://creativecommons.org/licenses/by/4.0/ |
Document type:
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Article |
Published by:
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Uri:
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https://ddd.uab.cat/record/253850
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