Soybean isoflavones inhibit tumor necrosis factor-α-induced apoptosis and the production of interleukin-6 and prostaglandin E2 in osteoblastic cells

The effects of individual soybean isoflavones, genistein (4',5,7-trihydroxyisoflavone) and daidzein (4',7-dihydroxyisoflavone), on tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis and the production of local factors in osteoblastic cells has been investigated. Soybean isoflavones increased DNA synthesis and the number of viable cells. When cells were treated with TNF-alpha, the number of viable cells dose-dependently decreased. The decrease in cell number caused by TNF-alpha treatment was due to apoptosis, which was confirmed by TUNEL and cell death ELISA analyses. Soybean isoflavones inhibited apoptosis of osteoblastic cells subjected to TNF-alpha treatment. MC3T3-E1 osteoblastic cells secrete interleukin-6 (IL-6), interleukin-1beta (IL-1beta), nitric oxide (NO) and prostaglandin E-2 (PGE(2)) constitutively, but at low levels. Soybean isoflavones had no effect on the constitutive production of these local factors. When cells were treated with TNF-alpha (10(-10)M), the production of IL-6 and PGE(2), but not that of IL-1beta and NO, significantly increased. Treatment with soybean isoflavones (10(-5)M), in the presence of TNF-alpha (10(-10)M), for 48 h inhibited production of IL-6 and PGE(2), suggesting the antiresorptive action of soy phytoestrogen may be mediated by decreases in these local factors. The findings of this study thus suggest that soybean isoflavones may promote the function of osteoblastic cells and play an important role in bone remodeling. (C) 2003 Elsevier Science Ltd. All rights reserved.