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RESEARCH PRODUCT
SNPs in bone-related miRNAs are associated with the osteoporotic phenotype
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 Malouf SierraAntonio CanoJosé Luis Pérez-castrillonXavier Nogués SolánNatalia Garcia-giraltAdolfo Díez PérezUniversitat Autònoma De Barcelonasubject
0301 basic medicineconformation:Diseases::Wounds and Injuries::Fractures Bone::Hip Fractures [Medical Subject Headings]:Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings]Polimorfismo de nucleótido simpleGene ExpressionboneOsteoblastosDensidad ósea:Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]Cohort StudiesGene Frequencysingle nucleotide polymorphismBone DensityBone cellOssosgeneticsFracturas osteoporóticasCells CulturedGeneticsBone mineralMicroARNsMultidisciplinarymicroRNAbiologyQalleleR:Diseases::Wounds and Injuries::Fractures Bone::Osteoporotic Fractures [Medical Subject Headings]clinical trialMiddle Agedcohort analysisPhenotypeHumanosFenotipmedicine.anatomical_structureCancellous BoneosteoblastMedicine: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]AlelosFenotipomusculoskeletal diseasesmedicine.medical_specialtyGenotypeScienceSingle-nucleotide polymorphismBiologychemistryPolymorphism Single NucleotideArticleBone and Bones:Anatomy::Musculoskeletal System::Skeleton::Bone and Bones::Cancellous Bone [Medical Subject Headings]03 medical and health sciencesCalcification PhysiologicInternal medicinemicroRNAmedicineHumanshumanproceduresAllele:Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings]AllelesFemoral neckGenetic associationAgedcell 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]OsteoblastsEnfermedades óseasFracturas de caderaComputational BiologyCuello femoral:Chemicals and Drugs::Nucleic Acids Nucleotides and Nucleosides::Antisense Elements (Genetics)::RNA Antisense::MicroRNAs [Medical Subject Headings]MicroRNAs030104 developmental biologyEndocrinologymulticenter studybone mineralizationNucleic Acid ConformationOsteoporosispathology:Anatomy::Musculoskeletal System::Skeleton::Bone and Bones::Bones of Lower Extremity::Leg Bones::Femur::Femur Neck [Medical Subject Headings]TranscriptomemetabolismGenotipoFracturesdescription
AbstractBiogenesis 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-03-01 |