Design, Synthesis, and Osteogenic Activity of Daidzein Analogs on Human Mesenchymal Stem Cells

Abstract

Osteoporosis is caused by an overstimulation of osteoclast activity and the destruction of the bone extracellular matrix. Without the normal architecture, osteoblast cells are unable to rebuild phenotypically normal bone. Hormone replacement therapy with estrogen has been effective in increasing osteoblast activity but also has resulted in the increased incidence of breast and uterine cancer. In this study we designed and synthesized a series of daidzein analogs to investigate their osteogenic induction potentials. Human bone marrow derived mesenchymal stem cells (MSCs) from three different donors were treated with daidzein analogs and demonstrated enhanced osteogenesis when compared to daidzein treatment. The enhanced osteogenic potential of these daidzein analogs resulted in increased osterix (Sp7), alkaline phosphatase (ALP), osteopontin (OPN), and insulin-like growth factor 1 (IGF-1), which are osteogenic transcription factors that regulate the maturation of osteogenic progenitor cells into mature osteoblast cells.

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

“…The expression levels of Osx, and total and phosphorylated smad‐1/5/8 forms with respect to control improved noticeably exhibiting the strong anabolic nature of CP and VD in differentiating the osteoblasts. The results were similar to the previous studies on Dz in human mesenchymal stem cells and by Ge in in vitro where the expression intensities of Osx, total, and phosphorylated Smad, ALP, collagen, and OPN proteins amplified with respect to control …”

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

“…Jia et al (2003) found that daidzein increased the viability of osteoblasts, ALP activity, osteocalcin synthesis and BMP-2 expression in primary osteoblastic cells. Strong et al (2014) reported that daidzein enhanced the expression of some ostegenic genes in human bone marrow-derived mesenchymal stem cells (HBMSCs), such as Osx, ALP, and OPN. The stimulatory role of daidzein on the osteoblast differentiation and mineralization in MC3T3-E1 cells has also been reported (Ge et al 2006).…”

“…Daidzein, the most widely studied soy phytoestrogen, shows promise as a potential antiosteoporosis agent. Many reports have shown that daidzein has an effect not only on osteogenic activity, but also has anticancer activity (Adjaklyet al, 2013;Strong et al, 2014;Chen et al, 2015). Daidzein-enhanced osteoblast growth might be mediated through the upregulation of BMP expression in primary osteoblast cells (Jia et al, 2003).…”

Effects of daidzein on alveolar bone loss and internal microstructures of bone in a rat model of experimental periodontitis: a study using micro‐computed tomography

“…Daidzein treatment in a rat model of male osteoporosis increased tibial trabecular bone mass and decreased cancellous bone turnover . Daidzein also enhanced osteogenic differentiation of human bone marrow‐derived mesenchymal stem cells .…”