Role of Sost in Wnt signal pathway in osteoporosis rats and regulating effect of soybean isoflavones on Wnt signal pathway

Mol Biol Rep. 2014 Jul;41(7):4447-54. doi: 10.1007/s11033-014-3315-2. Epub 2014 Apr 24.

Abstract

To explore the mechanism of soybean isoflavones (SI) on OVX-induced osteoporosis, we investigated the effect of SI on Wnt signaling that emerged as a novel key pathway for promoting bone formation. Results showed that SI decreased bone mineral elements loss, improved biomechanics parameters in OVX rats. Wnt3a activation can promote the dissociation of β-catenin complexes, release of β-catenin monomer and inhibition of β-catenin monomer degradation. SI decreased sost mRNA and sclerosteosis protein expression in a dose-dependent manner, and increased β-catenin proteins expression in femur of OVX rats. These data suggest that SI suppresses the canonical Wnt signal in OVX rats, partially through the enhancement of the dickkopf-1 production. OVX results in decreased estrogen level in rats. SI act as inhibitors of Wnt-mediated activation of by competitively binding to LRP5, and subsequently downregulating β-catenin gene.

MeSH terms

  • Animals
  • Bone Density / drug effects
  • Bone Morphogenetic Proteins / antagonists & inhibitors
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Estrogens / metabolism
  • Female
  • Femur / drug effects*
  • Femur / metabolism
  • Femur / pathology
  • Gene Expression Regulation
  • Genetic Markers / genetics
  • Glycine max / chemistry*
  • Intercellular Signaling Peptides and Proteins / agonists
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Isoflavones / isolation & purification
  • Isoflavones / pharmacology*
  • Low Density Lipoprotein Receptor-Related Protein-5 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-5 / metabolism
  • Osteoporosis / genetics
  • Osteoporosis / metabolism
  • Osteoporosis / pathology
  • Osteoporosis / prevention & control*
  • Ovariectomy
  • Protein Binding
  • Proteolysis / drug effects
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Wnt Signaling Pathway / drug effects*
  • Wnt3A Protein / genetics
  • Wnt3A Protein / metabolism*
  • beta Catenin / antagonists & inhibitors
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Bone Morphogenetic Proteins
  • Ctnnb1 protein, rat
  • Dkk1 protein, rat
  • Estrogens
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • Isoflavones
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Lrp5 protein, rat
  • RNA, Messenger
  • Sost protein, rat
  • Wnt3A Protein
  • beta Catenin