Daidzein increases OPG/RANKL ratio and suppresses IL-6 in MG-63 osteoblast cells

• Daidzein increases OPG/RANKL expression ratio in MG-63 cells.
• Daidzein suppresses IL-6 expression in MG-63 cells.
• Daidzein increases OPG/RANKL ratio, suppresses IL-6 production through the ER pathway.
• The effects of daidzein on OPG/RANKL expression are mediated by both ERα and ERβ.
• The effects of daidzein on IL-6 production primarily by ERα

Daidzein is a major dietary source of isoflavones found in Leguminosae, and belongs to the family of diphenolic compounds. The estrogenic effects of daidzein to prompt bone formation and prevent bone resorption have been observed in animal models and cultured cells. In our study, we studied the effects of daidzein, raloxifene and E2 on expression of the osteoblast-produced bone regulatory factors OPG, RANKL and IL-6 in human osteoblastic MG-63 cells. Results suggest that treatment with daidzein, raloxifene and E2 increased the levels of OPG and decreased those of RANKL and IL-6. The effects of daidzein on OPG and RANKL expression are mediated by both ERα and ERβ but those on IL-6 production primarily by ERα. Moreover, daidzein may promote activation of the classic estrogen response element (ERE) pathway through increasing ERα, ERβ and steroid hormone receptor coactivator (SRC)-1 expression. E2 was also able to enhance transcription derived from the ERE, while raloxifene has no effect on it. Raloxifene increased ERα protein and gene expression levels but had no effect on ERβ protein and gene expression at 0.1 μM. E2 was found significantly increased the protein and mRNA levels of SRC-1, while raloxifene has no effect on it compared with control. This ability of daidzein to affect osteoblastic cells makes it a good candidate for the treatment of bone loss in postmenopausal women.

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