Role of Sost in Wnt signal pathway in osteoporosis rats and regulating effect of soybean isoflavones on Wnt signal pathway.
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.
Hands and Feet Microsurgery, The Second Hospital of Dalian Medical University, Dalian, 116023, People's Republic of China.
Hai Dong
HD
Liang
Fang
F
Yu
Ping
P
Lv
Zheng Nan
ZN
Zhao
Zhi Hong
ZH
Tong
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D007529:Isoflavones / Q000302:isolation & purification / Q000494:pharmacology*; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics / Q000378:metabolism; D010024:Osteoporosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010052:Ovariectomy; D011485:Protein Binding; D059748:Proteolysis / Q000187:drug effects; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013025:Glycine max / Q000737:chemistry*; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; C495268:Ctnnb1 protein, rat; C531384:Dkk1 protein, rat; D004967:Estrogens; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D007529:Isoflavones; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555484:Lrp5 protein, rat; D012333:RNA, Messenger; C486031:Sost protein, rat; D060509:Wnt3A Protein; D051176:beta Catenin