SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
| العنوان: | SNPs in bone-related miRNAs are associated with the osteoporotic phenotype |
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| المؤلفون: | 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 |
| المساهمون: | Universidad de Cantabria, [De-Ugarte,L, Caro-Molina,E, Rodríguez-Sanz,M, Nogues,X, Garcia-Giralt,N, Diez-Perez,A] IMIM (Hospital del Mar Medical Research Institute), Universitat Autònoma de Barcelona, CIBERFES, RETICEF (ISCIII), Barcelona, Spain. [García-Pérez,MA] Department of Genetics and Institute of Health Research INCLIVA, University of Valencia, Valencia, Spain. [Olmos,JM] 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,JA] Servicio de Medicina Interna, Complejo Hospitalario Universitario de Albacete, Albacete, Spain. [González-Macías,J] Departamento de Medicina Interna, H. Marqués de Valdecilla, Universidad de Cantabria, IDIVAL, RETICEF, Santander, Spain. [del Pino-Montes,J] Servicio de Reumatología. Hospital Universitario de Salamanca, RETICEF (ISCIII), IBSAL (Biomedical Research Institute of Salamanca), Salamanca, Spain. [Muñoz-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,JL] Hospital Universitario Río Hortega, Valladolid, Spain., This work was supported by RETICEF (RD12/0043/0022), CIBERFES (CB16/10/00245) and the Grant FIS PI10/01537, PI12/02775, PI12/02582, and PI13/00116 (Carlos III Health Institute, Science and Innovation Ministry), FIS and Grants from the Generalitat de Catalunya (DIUE 2014 SGR 775), '664367/FOCUS' project (EU Health Programme, 2014–2020) and FEDER funds have supported this study. |
| المصدر: | Zaguán. Repositorio Digital de la Universidad de Zaragoza instname Scientific Reports Sci Rep 2017 Mar 31; 7(1): 516 UCrea Repositorio Abierto de la Universidad de Cantabria Universidad de Cantabria (UC) Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, conformation, Diseases::Wounds and Injuries::Fractures, Bone::Hip Fractures [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Polimorfismo de nucleótido simple, Gene Expression, bone, Osteoblastos, Densidad ósea, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, Gene Frequency, single nucleotide polymorphism, Bone Density, Bone cell, Ossos, genetics, Fracturas osteoporóticas, Cells, Cultured, Genetics, Bone mineral, MicroARNs, Multidisciplinary, microRNA, biology, allele, Diseases::Wounds and Injuries::Fractures, Bone::Osteoporotic Fractures [Medical Subject Headings], clinical trial, Middle Aged, cohort analysis, Phenotype, Humanos, Fenotip, medicine.anatomical_structure, Cancellous Bone, osteoblast, Medicine, Diseases::Musculoskeletal Diseases::Bone Diseases [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Anatomy::Cells::Connective Tissue Cells::Osteoblasts [Medical Subject Headings], Alelos, Fenotipo, musculoskeletal diseases, medicine.medical_specialty, Genotype, Science, Single-nucleotide polymorphism, Biology, chemistry, Polymorphism, Single Nucleotide, Article, Bone and Bones, Anatomy::Musculoskeletal System::Skeleton::Bone and Bones::Cancellous Bone [Medical Subject Headings], 03 medical and health sciences, Calcification, Physiologic, Internal medicine, medicine, Humans, human, procedures, Allele, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings], Alleles, Femoral neck, Genetic association, Aged, cell culture, Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Bone Density [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Osteoblasts, Enfermedades óseas, Fracturas de cadera, Computational Biology, Cuello femoral, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [Medical Subject Headings], MicroRNAs, 030104 developmental biology, Endocrinology, multicenter study, bone mineralization, Nucleic Acid Conformation, Osteoporosis, pathology, Anatomy::Musculoskeletal System::Skeleton::Bone and Bones::Bones of Lower Extremity::Leg Bones::Femur::Femur Neck [Medical Subject Headings], Transcriptome, metabolism, Genotipo, Fractures |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1251-2664 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::70fb6fa5fe6dd604e7d66af1f80b0b6dTest http://zaguan.unizar.es/record/61509Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....70fb6fa5fe6dd604e7d66af1f80b0b6d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 12512664 20452322 |
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