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ARS Home » Southeast Area » New Orleans, Louisiana » Southern Regional Research Center » Food Processing and Sensory Quality Research » Research » Publications at this Location » Publication #296499

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

Author
item STRONG, AMY - TULANE UNIVERSITY
item BUROW, MATTHEW - TULANE UNIVERSITY
item BUNNELL, BRUCE - TULANE UNIVERSITY
item QUAN, JIANG - XAVIER UNIVERSITY
item GUANGDI, WANG - XAVIER UNIVERSITY
item QIANG, ZHANG - XAVIER UNIVERSITY
item SHILOH, ZHENG - XAVIER UNIVERSITY
item Boue, Stephen

Submitted to: ACS Medicinal Chemistry Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/12/2013
Publication Date: 12/10/2013
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. ACS Medicinal Chemistry Letters. 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.