RT info:eu-repo/semantics/article
T1 Contribution of genetic and epigenetic mechanisms to Wnt pathway activity in prevalent skeletal disorders
A1 García Ibarbia, Carmen
A1 Delgado Calle, Jesús
A1 Casafont, Íñigo
A1 Velasco Bernal, Javier
A1 Arozamena, Jana
A1 Pérez Núñez, María I.
A1 Alonso, María A.
A1 Berciano, María T.
A1 Ortiz, Fernando
A1 Pérez Castrillon, José Luis
A1 Fernández, Agustín F.
A1 Fraga, Mario F.
A1 Zarrabeitia Cimiano, María Teresa
A1 Riancho Moral, José Antonio
K1 Osteoporosis
K1 Cadera - Fracturas
AB We reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in 26osteoarthritis. We aimed to confirm those results by analyzing β-catenin levels and explored potential genetic 27and epigenetic mechanisms involved. 28β-Catenin gene expression and nuclear levelswere analyzed by real time PCR and confocal immunofluorescence. 29Increased nuclear β-catenin was found in osteoblasts isolated from patients with osteoarthritis (99 ± 4 30units vs. 76 ± 12, p = 0.01, n = 10), without differences in gene transcription, which is consistent with 31a post-translational down-regulation of β-catenin and decreased Wnt pathway activity. 32Twenty four single nucleotide polymorphisms (SNPs) of genes showing differential expression between fractures 33and osteoarthritis (WNT4, WNT10A, WNT16 and SFRP1) were analyzed in DNA isolated from blood of 853 pa- 34tients. The genotypic frequencies were similar in both groups of patients, with no significant differences. 35Methylation ofWnt pathway genes was analyzed in bone tissue samples (15 with fractures and 15 with osteo- 36arthritis) by interrogating a CpG-based methylation array. Six genes showed significant methylation differences 37between both groups of patients: FZD10, TBL1X, CSNK1E, WNT8A, CSNK1A1L and SFRP4. The DNA demethylating 38agent 5-deoxycytidine up-regulated 8 genes, including FZD10, in an osteoblast-like cell line, whereas it down- 39regulated other 16 genes. 40In conclusion,Wnt activity is reduced in patientswith hip fractures, in comparisonwith thosewith osteoarthritis. 41It does not appear to be related to differences in the allele frequencies of the Wnt genes studied. On the other 42hand, methylation differences between both groups could contribute to explain the differences inWnt activity
PB Elsevier B.V.
SN 0378-1119
YR 2013
FD 2013
LK http://uvadoc.uva.es/handle/10324/5865
UL http://uvadoc.uva.es/handle/10324/5865
LA eng
NO Gene, 2013, p. 1-8
NO Producción Científica
DS UVaDOC
RD 25-abr-2024