A low dose of daidzein acts as an ERbeta-selective agonist in trabecular osteoblasts of young female piglets.
The role of estrogens and estrogen-like molecules, including isoflavones, in regulating bone cell activities is essential in understanding the etiology and treatment of post-menopausal osteoporosis. Although estrogen replacement (HRT) has been the main therapy used to prevent and treat osteoporosis, there are concerns about its safety. Isoflavones have attracted attention to their potential roles in osteoporosis prevention and treatment. We have compared the effects of the isoflavone daidzein (1 nM), which has no effect on tyrosine kinases, and 17beta-estradiol (1 nM) on the development and function of cultured osteoblasts isolated from long bones of young female piglets. Daidzein increased ALP activity, osteocalcin secretion, and mineralization, while E2 increased only ALP activity. The content of ERbeta and osteoprotegerin secretion by control cells gradually increased during osteoblast differentiation, whereas the ERalpha and RANK-L content decreased. Daidzein enhanced only the nuclear ERbeta whereas estradiol increased both ERalpha and ERbeta. Daidzein and estradiol increased osteoprotegerin and RANK-L secretion. Daidzein had a more pronounced effect than did estradiol. Daidzein and estradiol increased the membrane content of RANK-L and the nuclear content of runx2/Cbfa1. Daidzein enhanced the nuclear content of progesterone and vitamin D receptors but not as much as did estradiol. All the effects of daidzein were blocked by ICI 182,780. We conclude that a low concentration of daidzein may exert its anti-resorptive action by increasing the activity of porcine mature osteoblasts via ERbeta, by regulating runx2/Cbfa1 production, and by stimulating the secretion of key proteins involved in osteoclastogenesis, such as osteoprotegerin and RANK-ligand.
De Wilde
Anne
A
Laboratoire de Nutrition et de Sécurité Alimentaire, Institut National de la Recherche Agronomique, Jouy-en-Josas, France.
Lieberherr
Michele
M
Colin
Colette
C
Pointillart
Alain
A
D000469:Alkaline Phosphatase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001842:Bone and Bones / Q000166:cytology*; D002118:Calcium / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit; D000242:Cyclic AMP / Q000032:analysis; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D006023:Glycoproteins / Q000032:analysis; D007529:Isoflavones / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015675:Osteocalcin / Q000187:drug effects / Q000378:metabolism; D053244:Osteoprotegerin; D011347:Procollagen / Q000032:analysis / Q000096:biosynthesis; D011374:Progesterone / Q000032:analysis; D053245:RANK Ligand; D018167:Receptors, Calcitriol / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis; D011960:Receptors, Estrogen / Q000819:agonists* / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor; D013552:Swine; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis
D002352:Carrier Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal; D006023:Glycoproteins; D007529:Isoflavones; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D053244:Osteoprotegerin; D011347:Procollagen; D053245:RANK Ligand; D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D018124:Receptors, Tumor Necrosis Factor; D014157:Transcription Factors; D015675:Osteocalcin; D000077267:Fulvestrant; D011374:Progesterone; D004958:Estradiol; C004742:daidzein; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D002118:Calcium