Effect of Soybean Isoflavones on the Apoptosis and the Responsiveness of Local Factors Induced by TNF-alpha in Osteoblastic Cells

다국어 초록 (Multilingual Abstract)

We have investigated the effects of individual soybean isoflavones, genistein (4,5,7-trihydroxyisoflavone) and daidzein (4,7-dihydroxyisoflavone), on tumor necrosis factor-α (TNF-α)-induced apoptosis and the production of local factors in osteoblastic cells. Soybean isoflavones increased DNA synthesis and the number of viable cells. When the cells were treated with TNF-α (10^(-11)M∼10^(-9) M), the number of viable cells was dose-dependently decreased. The decrease in the cell number caused by TNF-α treatment was due to apoptosis, which was manifested by TUNEL and cell death ELISA method. Soybean isoflavones inhibited the apoptosis of osteoblastic cells subjected to TNF-α treatment. It can be suggested that these isoflavones may be involved in maintaining the viability and proliferation of osteoblastic cells. MC3T3-E1 osteoblastic cells secrete IL-6, IL-1ß, NO and PGE₂ constitutively, but at low levels. Soybean isoflavones have no effect on the constitutive production of these local factors.
When the cells were treated with TNF-α (10^(-10)M), the production of IL-6 and PGE₂, but not that of IL-1ß and NO, was increased significantly. Treatment with soybean isoflavones (10^(-5)M) in the presence of TNF-α (10^(-10)M) for 48 hours inhibited the production of IL-6 and PGEz, suggesting the antiresorptive action of soy phytoestrogen may be mediated by decrease in these local factors.
The findings of this study suggest that the function of osteoblastic cells is promoted by soybean isoflavones, thereby playing an important role in bone remodeling.