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 a...
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Nature Portfolio
2017
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oai:doaj.org-article:b02685a070da4fae9bc27bc45550d8512021-12-02T11:52:34ZSNPs in bone-related miRNAs are associated with the osteoporotic phenotype10.1038/s41598-017-00641-72045-2322https://doaj.org/article/b02685a070da4fae9bc27bc45550d8512017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00641-7https://doaj.org/toc/2045-2322Abstract 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.Laura De-UgarteEnrique Caro-MolinaMaria Rodríguez-SanzMiguel Angel García-PérezJosé M. OlmosManuel Sosa-HenríquezRamón Pérez-CanoCarlos Gómez-AlonsoLuis Del RioJesús Mateo-AgudoJosé Antonio Blázquez-CabreraJesús González-MacíasJavier del Pino-MontesManuel Muñoz-TorresManuel Diaz-CurielJorge MaloufAntonio CanoJosé Luis Pérez-CastrillonXavier NoguesNatalia Garcia-GiraltAdolfo Diez-PerezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Laura De-Ugarte Enrique Caro-Molina Maria Rodríguez-Sanz Miguel Angel García-Pérez José M. Olmos Manuel Sosa-Henríquez Ramón Pérez-Cano Carlos Gómez-Alonso Luis Del Rio Jesús Mateo-Agudo José Antonio Blázquez-Cabrera Jesús González-Macías Javier del Pino-Montes Manuel Muñoz-Torres Manuel Diaz-Curiel Jorge Malouf Antonio Cano José Luis Pérez-Castrillon Xavier Nogues Natalia Garcia-Giralt Adolfo Diez-Perez SNPs in bone-related miRNAs are associated with the osteoporotic phenotype |
| description |
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 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. |
| format |
article |
| author |
Laura De-Ugarte Enrique Caro-Molina Maria Rodríguez-Sanz Miguel Angel García-Pérez José M. Olmos Manuel Sosa-Henríquez Ramón Pérez-Cano Carlos Gómez-Alonso Luis Del Rio Jesús Mateo-Agudo José Antonio Blázquez-Cabrera Jesús González-Macías Javier del Pino-Montes Manuel Muñoz-Torres Manuel Diaz-Curiel Jorge Malouf Antonio Cano José Luis Pérez-Castrillon Xavier Nogues Natalia Garcia-Giralt Adolfo Diez-Perez |
| author_facet |
Laura De-Ugarte Enrique Caro-Molina Maria Rodríguez-Sanz Miguel Angel García-Pérez José M. Olmos Manuel Sosa-Henríquez Ramón Pérez-Cano Carlos Gómez-Alonso Luis Del Rio Jesús Mateo-Agudo José Antonio Blázquez-Cabrera Jesús González-Macías Javier del Pino-Montes Manuel Muñoz-Torres Manuel Diaz-Curiel Jorge Malouf Antonio Cano José Luis Pérez-Castrillon Xavier Nogues Natalia Garcia-Giralt Adolfo Diez-Perez |
| author_sort |
Laura De-Ugarte |
| title |
SNPs in bone-related miRNAs are associated with the osteoporotic phenotype |
| title_short |
SNPs in bone-related miRNAs are associated with the osteoporotic phenotype |
| title_full |
SNPs in bone-related miRNAs are associated with the osteoporotic phenotype |
| title_fullStr |
SNPs in bone-related miRNAs are associated with the osteoporotic phenotype |
| title_full_unstemmed |
SNPs in bone-related miRNAs are associated with the osteoporotic phenotype |
| title_sort |
snps in bone-related mirnas are associated with the osteoporotic phenotype |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/b02685a070da4fae9bc27bc45550d851 |
| work_keys_str_mv |
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| _version_ |
1718395005069950976 |