000061509 001__ 61509
000061509 005__ 20190709135534.0
000061509 0247_ $$2doi$$a10.1038/s41598-017-00641-7
000061509 0248_ $$2sideral$$a98475
000061509 037__ $$aART-2017-98475
000061509 041__ $$aeng
000061509 100__ $$aDe-Ugarte, L.
000061509 245__ $$aSNPs in bone-related miRNAs are associated with the osteoporotic phenotype
000061509 260__ $$c2017
000061509 5060_ $$aAccess copy available to the general public$$fUnrestricted
000061509 5203_ $$aBiogenesis 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.
000061509 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/RD12-0043-0022$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI13-00116$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-02775$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-02582$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI10-01537$$9info:eu-repo/grantAgreement/ES/ISCIII/CB16-10-00245
000061509 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000061509 590__ $$a4.122$$b2017
000061509 591__ $$aMULTIDISCIPLINARY SCIENCES$$b12 / 64 = 0.188$$c2017$$dQ1$$eT1
000061509 592__ $$a1.533$$b2017
000061509 593__ $$aMultidisciplinary$$c2017$$dQ1
000061509 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000061509 700__ $$aCaro-Molina, E.
000061509 700__ $$aRodríguez-Sanz, M.
000061509 700__ $$aGarciá-Pérez, M. A.
000061509 700__ $$aOlmos, J. M.
000061509 700__ $$aSosa-Henríquez, M.
000061509 700__ $$aPérez-Cano, R.
000061509 700__ $$aGómez-Alonso, C.
000061509 700__ $$aDel Rio, L.
000061509 700__ $$0(orcid)0000-0001-7516-4737$$aMateo-Agudo, J.$$uUniversidad de Zaragoza
000061509 700__ $$aBlázquez-Cabrera, J. A.
000061509 700__ $$aGonzález-Maciás, J.
000061509 700__ $$aPino-Montes, J.
000061509 700__ $$aMunõz-Torres, M.
000061509 700__ $$aDIaz-Curiel, M.
000061509 700__ $$aMalouf, J.
000061509 700__ $$aCano, A.
000061509 700__ $$aPérez-Castrillon, J. L.
000061509 700__ $$aNogues, X.
000061509 700__ $$aGarcia-Giralt, N.
000061509 700__ $$aDIez-Perez, A.
000061509 7102_ $$11004$$2830$$aUniversidad de Zaragoza$$bDpto. Cirugía,Ginecol.Obstetr.$$cÁrea Traumatología y Ortopedia
000061509 773__ $$g7 (2017), 516 [10 pp.]$$pSci. rep.$$tScientific reports$$x2045-2322
000061509 8564_ $$s1657353$$uhttps://zaguan.unizar.es/record/61509/files/texto_completo.pdf$$yVersión publicada
000061509 8564_ $$s113787$$uhttps://zaguan.unizar.es/record/61509/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000061509 909CO $$ooai:zaguan.unizar.es:61509$$particulos$$pdriver
000061509 951__ $$a2019-07-09-12:03:44
000061509 980__ $$aARTICLE