Abstract: ß-catenin is a major contributor to the Wnt signalling cascade. We reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in osteoarthritis. In this study we analyzed ?-catenin levels and explored if differences in sclerostin expression, an osteocyte-derived Wnt inhibitor, explain the differences in Wnt activity in these disorders. Bone samples were obtained during hip arthroplasty. ß-catenin expression was analyzed by immunofluorescence and gene expression by RT-quantitative real time PCR. Sclerostin protein was detected in bone by immunofluorescence and in serum by ELISA. Less nuclear ?-catenin was found in osteoblast cultures from patients with fractures than with osteoarthritis (76± 12 vs 99±4 units, p= 0.01), without differences in ?-catenin gene transcription, consistent with decreased Wnt pathway activity. Osteocalcin expression was lower in hip fracture bone samples. However, no differences existed regarding sclerostin and alkaline phosphatase expression. The proportion of sclerostin-positive osteocytic lacunae tended to be lower in fractures (45.6±17.5 % vs 59.9± 17.9 %; p= 0.13). The number of osteocyte-containing lacunae was lower in fractures (59.2± 6.0 % vs 74.8± 8.5%, p= 0.001), but the proportion of sclerostin-positive osteocytes was similar in both groups. Sclerostin positive lacunae were located deeper in bone trabeculae than sclerostin-negative ones. Serum levels of sclerostin were also similar in both groups. These results show that, in comparison with osteoarthritis, Wnt activity is reduced in patients with hip fractures, but it does not appear to be due to an increased expression of sclerostin. The higher number of empty lacunae suggests that osteocytic death may contribute to fracture risk.

Autoría

Descargar referencia