Insights into the antiosteoporotic mechanism of the soy-derived isoflavone genistein: Modulation of the Wnt/beta-catenin signaling

Bone remodeling is a process that involves osteoblasts, osteoclasts, and osteocytes, and different intracellular signaling, such as the canonical Wnt/β-catenin pathway. Dysregulations of this pathway may also occur during secondary osteoporosis, as in the case of glucocorticoid-induced osteoporosis (GIO), which accelerates osteoblast and osteocyte apoptosis by reducing bone formation, osteoblast differentiation and function, accelerates in turn osteoblast, and osteocyte apoptosis. Genistein is a soy-derived nutrient belonging to the class of isoflavones that reduces bone loss in osteopenic menopausal women, inhibiting bone resorption; however, genistein may also favor bone formation. The aim of this study was to investigate whether estrogen receptor stimulation by genistein might promote osteoblast and osteocyte function during glucocorticoid challenge. Primary osteoblasts, collected from C57BL6/J mice, and MLO-A5 osteocyte cell line were used to reproduce an in vitro model of GIO by adding dexamethasone (1 μM) for 24 h. Cells were then treated with genistein for 24 h and quantitative Polymerase Chain Reaction (qPCR) and western blot were performed to study whether genistein activated the Wnt/β-catenin pathway. Dexamethasone challenge reduced bone formation in primary osteoblasts and bone mineralization in osteocytes; moreover, canonical Wnt/β-catenin pathway was reduced following incubation with dexamethasone in both osteoblasts and osteocytes. Genistein reverted these changes and this effect was mediated by both estrogen receptors α and β. These data suggest that genistein could induce bone remodeling through Wnt/β-catenin pathway activation.