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
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Animals
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Bone Density / drug effects
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Bone Morphogenetic Proteins / antagonists & inhibitors
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / metabolism
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Estrogens / metabolism
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Female
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Femur / drug effects*
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Femur / metabolism
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Femur / pathology
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Gene Expression Regulation
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Genetic Markers / genetics
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Glycine max / chemistry*
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Intercellular Signaling Peptides and Proteins / agonists
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism
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Isoflavones / isolation & purification
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Isoflavones / pharmacology*
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Low Density Lipoprotein Receptor-Related Protein-5 / genetics
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Low Density Lipoprotein Receptor-Related Protein-5 / metabolism
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Osteoporosis / genetics
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Osteoporosis / metabolism
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Osteoporosis / pathology
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Osteoporosis / prevention & control*
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Ovariectomy
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Protein Binding
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Proteolysis / drug effects
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RNA, Messenger / antagonists & inhibitors
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Wnt Signaling Pathway / drug effects*
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Wnt3A Protein / genetics
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Wnt3A Protein / metabolism*
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beta Catenin / antagonists & inhibitors
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beta Catenin / genetics
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beta Catenin / metabolism
Substances
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Bone Morphogenetic Proteins
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Ctnnb1 protein, rat
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Dkk1 protein, rat
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Estrogens
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Genetic Markers
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Intercellular Signaling Peptides and Proteins
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Isoflavones
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Low Density Lipoprotein Receptor-Related Protein-5
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Lrp5 protein, rat
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RNA, Messenger
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Sost protein, rat
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Wnt3A Protein
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beta Catenin