Inhibitory effect of genistein on bone resorption in tissue culture

Abstract

The effect of genistein on bone resorption in vitro was investigated. Femoral-metaphyseal tissues obtained from elderly female rats were cultured for 48 hr in Dulbecco's modified Eagle's medium (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin. The experimental cultures contained 10 −7 to 10 −3 M genistein. The bone-resorbing factors parathyroid hormone (1–34) (PTH; 10 −7 M), prostaglandin E 2 (PGE 2; 10 −5 M), and lipopolysaccharide (10 μg/mL) caused a significant decrease in bone calcium content. The decrease in bone calcium content induced by bone-resorbing factors was inhibited completely by genistein (10 −7 to 10 −5 M). In addition, this isoflavonoid (10 −5 M) completely inhibited the PTH (10 −7 M)- or PGE 2 (10 −5 M)-induced increase in medium glucose consumption and lactic acid production by bone tissues. Moreover, genistein (10 −5 M) blocked both PTH (10 −7 M)-increased acid phosphatase and -decreased alkaline phosphatase activities of bone tissues. The inhibitory effect of genistein (10 −5 M) on PTH (10 −7 M)-stimulated bone resorption was clearly prevented by the presence of 10 −6 M tamoxifen, an anti-estrogen reagent. Genistein (10 −5 M) did not further enhance the inhibitory effect of estrogen (10 −9 M) on PTH-stimulated bone resorption. These findings indicate that genistein has a direct inhibitory effect on bone resorption in tissue culture in vitro.