SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
Por:
De-Ugarte L., Caro-Molina E., Rodríguez-Sanz M., Garciá-Pérez M.A., Olmos J.M., Sosa-Henríquez M., Pérez-Cano R., Gómez-Alonso C., Del Rio L., Mateo-Agudo J., Blázquez-Cabrera J.A., González-Maciás J., Pino-Montes J.D., Munõz-Torres M., DIaz-Curiel M., Malouf J., Cano A., Pérez-Castrillon J.L., Nogues X., Garcia-Giralt N., DIez-Perez A.
Publicada:
1 ene 2017
Resumen:
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. © 2017 The Author(s).
Filiaciones:
De-Ugarte L.:
IMIM (Hospital Del Mar Medical Research Institute), Universitat Autònoma de Barcelona, CIBERFES, RETICEF (ISCIII), Barcelona, Spain
Caro-Molina E.:
IMIM (Hospital Del Mar Medical Research Institute), Universitat Autònoma de Barcelona, CIBERFES, RETICEF (ISCIII), Barcelona, Spain
Rodríguez-Sanz M.:
IMIM (Hospital Del Mar Medical Research Institute), Universitat Autònoma de Barcelona, CIBERFES, RETICEF (ISCIII), Barcelona, Spain
Garciá-Pérez M.A.:
Department of Genetics and Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain
Olmos J.M.:
Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla-IDIVAL, Hospital de Torrelavega, Universidad de Cantabria, RETICEF, Santander, Spain
Sosa-Henríquez M.:
Unidad Metabólica Ósea, Hospital Universitario Insular, Universidad de Las Palmas de Gran Canaria, Canarias, Spain
Pérez-Cano R.:
Departamento de Medicina (USE), UGC Medicina Interna, Hospital Universitario Virgen Macarena, Seville, Spain
Gómez-Alonso C.:
Servicio de Metabolismo Óseo y Mineral, Hospital Universitario Central de Asturias, Oviedo, Spain
Del Rio L.:
CETIR Grup Mèdic, RETICEF, Barcelona, Spain
Mateo-Agudo J.:
Servicio COT, Hospital Universitario Miguel Servet, Zaragoza, Spain
Blázquez-Cabrera J.A.:
Servicio de Medicina Interna, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
González-Maciás J.:
Departamento de Medicina Interna H. Marqués de Valdecilla, Universidad de Cantabria, IDIVAL, RETICEF, Santander, Spain
Pino-Montes J.D.:
Servicio de Reumatologiá, Hospital Universitario de Salamanca, RETICEF (ISCIII), IBSAL (Biomedical Research Institute of Salamanca), Salamanca, Spain
Munõz-Torres M.:
UGC Endocrinologia y Nutrición, Hospital Universitario San Cecilio. Granada, RETICEF, Ibs, Granada, Spain
DIaz-Curiel M.:
Unidad de Enfermedades Metabólicas Óseas, Servicio de Medicina Interna, Fundacion Jimenez Diaz, Madrid, Spain
Malouf J.:
Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain
Cano A.:
Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, INCLIVA, Valencia, Spain
Pérez-Castrillon J.L.:
Hospital Universitario Rió Hortega, Valladolid, Spain
Nogues X.:
IMIM (Hospital Del Mar Medical Research Institute), Universitat Autònoma de Barcelona, CIBERFES, RETICEF (ISCIII), Barcelona, Spain
Garcia-Giralt N.:
IMIM (Hospital Del Mar Medical Research Institute), Universitat Autònoma de Barcelona, CIBERFES, RETICEF (ISCIII), Barcelona, Spain
DIez-Perez A.:
IMIM (Hospital Del Mar Medical Research Institute), Universitat Autònoma de Barcelona, CIBERFES, RETICEF (ISCIII), Barcelona, Spain
All Open Access, Gold
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