Contribution of genetic and epigenetic mechanisms to Wnt pathway activity in prevalent skeletal disorders.

article i nfo Article history: Accepted 23 September 2013 Available online xxxx We reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in osteoarthritis. We aimed to confirm those results by analyzing β-catenin levels and explored potential genetic and epigenetic mechanisms involved. β-Cateningene expression and nuclear levelswereanalyzedby real timePCR and confocalimmunofluorescence. Increased nuclear β-catenin was found in osteoblasts isolated from patients with osteoarthritis (99 ± 4 units vs. 76 ± 12, p = 0.01, n = 10), without differences in gene transcription, which is consistent with a post-translational down-regulation of β-catenin and decreased Wnt pathway activity. Twentyfoursinglenucleotidepolymorphisms(SNPs)ofgenesshowingdifferentialexpressionbetweenfractures