Osteoinductive effects of glyceollins on adult mesenchymal stromal/stem cells from adipose tissue and bone marrow

Authors: BATEMAN, MARJORIE - Tulane University; STRONG, AMY - Tulane University; HUNTER, RYAN - Tulane University; BRATTON, MELYSSA - Xavier University; KOMATI, RAJESH - Xavier University; SRIDHAR, JAYALAKSHMI - Xavier University; RILEY, KEVIN - Xavier University; WANG, GUANGDI - Xavier University; HAYES, DANIEL - Louisiana State University; Boue, Stephen; BUROW, MATTHEW - Tulane University; BUNNELL, BRUCE - Tulane University

Submitted to: Phytomedicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/12/2017
Publication Date: 2/12/2017
Citation: Bateman, M., Strong, A., Hunter, R., Bratton, M.R., Komati, R., Sridhar, J., Riley, K.E., Wang, G., Hayes, D., Boue, S.M., Burow, M., Bunnell, B. 2017. Osteoinductive effects of glyceollins on adult mesenchymal stromal/stem cells from adipose tissue and bone marrow. Phytomedicine. doi:10.1016/j.phymed.2017.02.003.

Interpretive Summary: Osteoporosis is characterized by destruction of bone architecture, resulting in decreased bone mass density and increased fracture susceptibility. While current therapies focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabolic therapy candidates include phytoestrogens from soybean, such as daidzein and genistein, which effectively induce osteogenesis of adipose-derived stromal cells and bone marrow stromal cells. Glyceollins are structurally similar to daidzein, and herein, the osteoinductive effects of glyceollin I, glyceollin II, and a mixture of glyceollins I, II, and III (glyceollin mix) in both cell types were assessed and compared to estradiol. In adherent cultures, both cell types treated with estradiol, glyceollin I, glyceollin II, or glyceollin mix demonstrated increased calcium deposition relative to vehicle-treated cells. During evaluation on scaffolds seeded with cells, glyceollin II was the most efficacious in inducing cell osteogenesis compared to estradiol, glyceollin I and glyceollin mix. Dose-response analysis revealed that glyceollin II has the highest potency in tissue scaffold cultures. At all doses, osteoinductive effects were attenuated by fulvestrant, suggesting that glyceollin II acts at least in part through estrogen receptor-mediated pathways to induce osteogenesis. These results indicate that glyceollins hold the potential for the development of pharmacological interventions to improve clinical outcomes of patients with osteoporosis.

Technical Abstract: Osteoporosis is characterized by destruction of bone architecture, resulting in decreased bone mass density (BMD) and increased fracture susceptibility. While current therapies focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabolic therapy candidates include phytoestrogens, such as daidzein and genistein, which effectively induce osteogenesis of adipose-derived stromal cells (ASCs) and bone marrow stromal cells (BMSCs). Glyceollins are structural derivatives of daidzein, and herein, the osteoinductive effects of glyceollin I, glyceollin II, and a mixture of glyceollins I, II, and III (glyceollin mix) in ASCs and BMSCs were assessed and compared to estradiol. In adherent cultures, ASCs and BMSCs treated with estradiol, glyceollin I, glyceollin II, or glyceollin mix demonstrated increased calcium deposition relative to vehicle-treated cells. During evaluation on PLGA scaffolds seeded with ASCs and BMSCs, glyceollin II was the most efficacious in inducing ASC and BMSC osteogenesis compared to estradiol, glyceollin I and glyceollin mix. Dose-response analysis in ASCs and BMSCs revealed that glyceollin II has the highest potency at 10 nM in adherent cultures and 1 µM in tissue scaffold cultures. At all doses, osteoinductive effects were attenuated by fulvestrant, suggesting that glyceollin II acts at least in part through estrogen receptor-mediated pathways to induce osteogenesis. Analysis of gene expression demonstrated that, similar to estradiol, glyceollin II induces upregulation of genes involved in osteogenic differentiation. These results indicate that glyceollins hold the potential for the development of pharmacological interventions to improve clinical outcomes of patients with osteoporosis.