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United States Department of Agriculture

Agricultural Research Service

Research Project: Rice as a Source and Delivery System for Nutrients and Lipophilic Bioactive Compounds

Location: Food Processing and Sensory Quality Research

Title: Design, synthesis, and osteogenic activity of daidzein analogs on human mesenchymal stem cells

Authors
item Strong, Amy -
item Burow, Matthew -
item Bunnell, Bruce -
item Quan, Jiang -
item Guangdi, Wang -
item Qiang, Zhang -
item Shiloh, Zheng -
item BOUE, STEPHEN

Submitted to: Journal of Medicinal Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 12, 2013
Publication Date: December 10, 2013
Citation: Strong, A., Burow, M., Bunnell, B., Quan, J., Guangdi, W., Qiang, Z., Shiloh, Z., Boue, S.M. 2013. Design, synthesis, and osteogenic activity of daidzein analogs on human mesenchymal stem cells. Journal of Medicinal Chemistry. 5(2):143-148.

Interpretive Summary: Osteoporosis, defined by the loss of bone mass and strength, results in the loss of structural and mechanical support in bone, and leads to an increased risk of fractures. Hormone replacement therapy with estrogen has been efficacious at increasing bone building activity, but also has resulted in the increased incidence of breast and uterine cancer. Other plant-derived estrogens or phytoestrogens, such as daidzein, (found in soy) has recently been investigated, and shown to have osteogenic (bone producing) activity. We have designed and synthesized a series of daidzein analogs to investigate the osteogenic induction of these compounds. Human bone marrow derived from mesenchymal stem cells (MSCs) from three different donors were treated with daidzein analogs, and demonstrated enhanced bone building activity when compared to estrogen or daidzein. The enhanced osteogenic potential of these daidzein analogs resulted in increased gene expression of several proteins that regulate cells involved in bone production.

Technical Abstract: Osteoporosis, defined by the loss of bone mass and strength, results in the loss of structural and mechanical support in bone, and leads to an increased risk of fractures. In the adult skeleton, the bone undergoes continuous resorption carried out by osteoclast cells, and formation by osteoblast cells to regulate the amount of bone present. With osteoporosis, an overstimulation of osteoclast activity is observed, resulting in 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 efficacious at increasing osteoblast activity, but also has resulted in the increased incidence of breast and uterine cancer. Other plant-derived estrogens or phytoestrogens, such as daidzein, has recently been investigated and showed to have osteogenic activity; therfore, we have designed and synthesized a series of daidzein analogs to investigate the osteogenic induction of these compounds. Human bone marrow derived mesenchymal stem cells (MSCs) from three different donors were treated with daidzein analogs, and demonstrated enhanced osteogenesis when compared to estrogen or daidzein. 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.

Last Modified: 9/10/2014
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