Daidzein promotes osteoblast proliferation and differentiation in OCT1 cells through stimulating the activation of BMP-2/Smads pathway

Abstract

ABSTRACT. Daidzein, the most widely studied soy phytoestrogen, is not only a potential antiosteoporosis agent owing to its possible osteogenic activity, but also shows anticancer activity. However, the mechanisms through which daidzein affects osteoblast function have not been investigated thoroughly. Here, we show that daidzein stimulated cell proliferation and differentiation of osteoblasts, demonstrated by upregulation of XTT activity, enhancement of alkaline phosphatase (ALP) activity, and upregulation of osteoblast-specific marker genes, including Runt-related transcription factor 2 (Runx2) and Smad1, as well as upregulation of Runx2 and Smad1 protein expression. To determine the mechanisms underlying daidzein's effects on osteoblast differentiation, we first tested the role of daidzein in bone morphogenetic protein (BMP)-2 gene expression in OCT1 cells, and found that it significantly upregulated the expression of BMP-2. Furthermore, it significantly enhanced the phosphorylated protein level of Smad1/5/8 and the protein level of Osterix and increased the activity of 12xSBE-OC-Luc. Finally, we demonstrated that daidzein stimulated Col I, Runx2, and ALP expression, while these effects were significantly blocked by the BMP signaling inhibitor noggin. Together, our data indicate that daidzein acts through stimulating the activation of BMP-2/Smads pathway to promote osteoblast proliferation and differentiation.

Isoflavones rich cowpea and vitamin D induces the proliferation and differentiation of human osteoblasts via BMP‐2/Smad pathway activation: Mechanistic approach

“…BMP antagonist diminished the gene expression of the markers namely ALP, Collagen OPN, and total and phosphorylated Smad‐1/5/8 levels. The findings of our study with CP and VD were coherent with earlier reports where noggin influenced the expression levels of the genes ALP, Collagen, OPN and t‐Smad‐1/5/8 and p‐Smad‐1/5/8 . However, the expression levels of the OSX transcription factor were quite unpredicted after noggin treatment because the expression was completely abolished in all combination and individual groups of Dz and VD and combination groups of CP and Ge alone.…”

The antimicrobial peptide KR-12 promotes the osteogenic differentiation of human bone marrow stem cells by stimulating BMP/SMAD signaling

“…42,63 Several natural or chemical agents, including rapamycin, daidzein, and syringetin, have been reported to induce osteoblastic differentiation by inducing BMP and/or SMAD signaling. [64][65][66] This study showed that BMP2 expression was enhanced and SMAD1/5 phosphorylation as signicantly increased in KR-12-treated HBMSCs. KR-12-mediated SMAD1/5 activation was blocked by the TGFb/SMAD antagonist LDN-193189 HCL, and HBMSC differentiation was also attenuated.…”

Bone Protective Effect of Extra-Virgin Olive Oil Phenolic Compounds by Modulating Osteoblast Gene Expression

“…For instance, flavonoids from natural extracts (e.g., icariin or naringin) were found to stimulate bone tissue regeneration by acting on the BMP signaling pathway, favoring the production of molecules closely related to bone metabolism, including ALP, OSC, and OPN [32,33,34,35]. Likewise, daidzein, a soy phytoestrogen, was reported to stimulate osteoblast proliferation and differentiation by activating the BMP/Smad signaling pathway [36].…”