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Abstract: SA-PO213

Increased Expression of DKK-1 in an Adynamic Bone Disease Model: Role of Phosphate

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Truyts, Tânia Priante de Oliveira Madid, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Ferreira, Juliana Cunha, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Neves, Katia R., Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Oliveira, Ivone Braga de, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Dominguez, Wagner, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Jorgetti, Vanda, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • Moyses, Rosa M.A., Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
  • dos Reis, Luciene, Universidade de Sao Paulo, Sao Paulo, São Paulo, Brazil
Background

Adynamic Bone Disease (ABD) is a common complication of Chronic Kidney Disease(CKD). We have previously shown that the Wnt/βcatenin signalling pathway is inhibited in the early stages of CKD, in association with an increased bone expression of sclerostin. DKK1 is also increased in CKD in a high-turnover animal model characterized by high phosphate (P) and PTH levels. Here we tested whether DKK1 expression is increased in an ABD model, trying to identify the isolated effects of P on this pathway.

Methods

Wistar rats were submitted to 5/6 nephrectomy (NX) and Parathyroidectomy (PTX). They were divided into 3 groups that underwent pair-feeding with different concentrations of P. Bone expression of sclerostin, Dkk1 and βCatenin was evaluated using mRNA levels and immunohistochemistry (IH), whereas FGF23 was evaluated by IH.

Results

NX animals presented higher levels of creatinine and P, but lower serum FGF23 (figure). Compared with SHAM, a high-P diet was associated with an increase in SOST and DKK1 mRNA levels, which was corrected by a decrease in P content in the diet. In IH, a high-P diet was associated with increased osteocytic expression of FGF23 and DKK1, but not sclerostin. A low-P diet increased active βcatenin IH expression. A significant correlation between bone FGF23 and DKK1 expression (r=0.5628; p=0.0028) was observed.

Conclusion

ABD is associated with a high bone expression of DKK1 and FGF23, which was normalized by P diet restriction. Our results suggest that in a low PTH environment, decreasing P content in the diet can stimulate the Wnt/βcatenin pathway. These findings have to be confirmed in a clinical scenario.

Funding

  • Government Support – Non-U.S.