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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, Javier
Arozamena, Jana
Pérez-Núñez, María I.
Alonso, María A.
Berciano, María T.
Ortiz, Fernando
Pérez Castrillón, José Luis
Fernández, Agustín F.
Fraga, Mario F.
Zarrabeitia, María T.
Riancho, José A.
Año del Documento: 2013
Editorial: Elsevier B.V.
Descripción: Producción Científica
Documento Fuente: Gene, 2013, p. 1-8
Resumen: 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: info:eu-repo/semantics/openAccess
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