De-Ugarte, LauraCaro-Molina, EnriqueRodríguez-Sanz, MariaGarcía-Pérez, Miguel AngelOlmos, José MSosa-Henríquez, ManuelPérez-Cano, RamónGómez-Alonso, CarlosDel Rio, LuisMateo-Agudo, JesúsBlázquez-Cabrera, José AntonioGonzález-Macías, JesúsDel Pino-Montes, JavierMuñoz-Torres, ManuelDiaz-Curiel, ManuelMalouf, JorgeCano, AntonioPérez-Castrillon, José LuisNogues, XavierGarcia-Giralt, NataliaDiez-Perez, Adolfo2017-05-092017-05-092017-03-31De-Ugarte L, Caro-Molina E, Rodríguez-Sanz M, García-Pérez MA, Olmos JM, Sosa-Henríquez M et al.SNPs in bone-related miRNAs are associated with the osteoporotic phenotype. Sci Rep. 2017 Mar 31;7(1):516.http://hdl.handle.net/10668/2644Biogenesis 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.enAlelosDensidad óseaEnfermedades óseasCuello femoralFracturas de caderaGenotipoHumanosMicroARNsOsteoblastosFracturas osteoporóticasFenotipoPolimorfismo de nucleótido simpleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::AllelesMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Bone DensityMedical Subject Headings::Diseases::Musculoskeletal Diseases::Bone DiseasesCancellous BoneMedical Subject Headings::Anatomy::Musculoskeletal System::Skeleton::Bone and Bones::Bones of Lower Extremity::Leg Bones::Femur::Femur NeckMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::GenotypeMedical Subject Headings::Diseases::Wounds and Injuries::Fractures, Bone::Hip FracturesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAsMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::OsteoblastsMedical Subject Headings::Diseases::Wounds and Injuries::Fractures, Bone::Osteoporotic FracturesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::PhenotypeMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single NucleotideMedical Subject Headings::Anatomy::Musculoskeletal System::Skeleton::Bone and Bones::Cancellous Boneresearch article28364128open access10.1038/s41598-017-00641-72045-2322PMC5391928