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    Por favor, use este identificador para citar o enlazar este ítem:http://uvadoc.uva.es/handle/10324/5865

    Título
    Contribution of genetic and epigenetic mechanisms to Wnt pathway activity in prevalent skeletal disorders
    Autor
    García Ibarbia, Carmen
    Delgado Calle, Jesús
    Casafont, Íñigo
    Velasco Bernal, JavierAutoridad UVA
    Arozamena, Jana
    Pérez Núñez, María I.
    Alonso, María A.
    Berciano, María T.
    Ortiz, Fernando
    Pérez Castrillon, José LuisAutoridad UVA
    Fernández, Agustín F.
    Fraga, Mario F.
    Zarrabeitia Cimiano, María Teresa
    Riancho Moral, José Antonio
    Año del Documento
    2013
    Editorial
    Elsevier B.V.
    Descripción
    Producción Científica
    Documento Fuente
    Gene, 2013, p. 1-8
    Resumo
    We reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in 26 osteoarthritis. We aimed to confirm those results by analyzing β-catenin levels and explored potential genetic 27 and epigenetic mechanisms involved. 28 β-Catenin gene expression and nuclear levelswere analyzed by real time PCR and confocal immunofluorescence. 29 Increased nuclear β-catenin was found in osteoblasts isolated from patients with osteoarthritis (99 ± 4 30 units vs. 76 ± 12, p = 0.01, n = 10), without differences in gene transcription, which is consistent with 31 a post-translational down-regulation of β-catenin and decreased Wnt pathway activity. 32 Twenty four single nucleotide polymorphisms (SNPs) of genes showing differential expression between fractures 33 and osteoarthritis (WNT4, WNT10A, WNT16 and SFRP1) were analyzed in DNA isolated from blood of 853 pa- 34 tients. The genotypic frequencies were similar in both groups of patients, with no significant differences. 35 Methylation ofWnt pathway genes was analyzed in bone tissue samples (15 with fractures and 15 with osteo- 36 arthritis) by interrogating a CpG-based methylation array. Six genes showed significant methylation differences 37 between both groups of patients: FZD10, TBL1X, CSNK1E, WNT8A, CSNK1A1L and SFRP4. The DNA demethylating 38 agent 5-deoxycytidine up-regulated 8 genes, including FZD10, in an osteoblast-like cell line, whereas it down- 39 regulated other 16 genes. 40 In conclusion,Wnt activity is reduced in patientswith hip fractures, in comparisonwith thosewith osteoarthritis. 41 It does not appear to be related to differences in the allele frequencies of the Wnt genes studied. On the other 42 hand, methylation differences between both groups could contribute to explain the differences inWnt activity
    Materias (normalizadas)
    Osteoporosis
    Cadera - Fracturas
    ISSN
    0378-1119
    Revisión por pares
    SI
    DOI
    10.1016/j.gene.2013.09.080
    Idioma
    eng
    URI
    http://uvadoc.uva.es/handle/10324/5865
    Derechos
    openAccess
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    • DEP52 - Artículos de revista [182]
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    CASTRILLON 14[1].pdf
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    Attribution-NonCommercial-NoDerivatives 4.0 InternationalExceto quando indicado o contrário, a licença deste item é descrito como Attribution-NonCommercial-NoDerivatives 4.0 International

    Universidad de Valladolid

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