Inhibitory effect of genistein on bone resorption in tissue culture.
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 E2 (PGE2; 10(-5) M), and lipopolysaccharide ( 10 microg/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 PGE2 (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.
Yamaguchi
M
M
Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, Shizuoka City, Japan.
Gao
Y H
YH
D000135:Acid Phosphatase / Q000187:drug effects / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D046508:Culture Techniques; D015232:Dinoprostone / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D010120:Oxytocics / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology
D004965:Estrogen Antagonists; D006131:Growth Inhibitors; D010120:Oxytocics; D010281:Parathyroid Hormone; D013629:Tamoxifen; D019833:Genistein; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D015232:Dinoprostone; D002118:Calcium