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Down‐Regulation of Osteoclast Differentiation by Daidzein via Caspase 3
Author(s) -
Rassi Claudia Maria,
Lieberherr Michele,
Chaumaz Gilles,
Pointillart Alain,
Cournot Giulia
Publication year - 2002
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2002.17.4.630
Subject(s) - daidzein , ovariectomized rat , osteoclast , medicine , endocrinology , chemistry , multinucleate , bone resorption , rankl , phytoestrogens , estrogen , bone marrow , acid phosphatase , genistein , in vitro , biology , biochemistry , microbiology and biotechnology , receptor , enzyme , activator (genetics)
Phytoestrogens are plant‐derived compounds with estrogen‐like activity. Phytoestrogen‐rich diets may prevent postmenopausal osteoporosis and these molecules maintain bone mass in ovariectomized animals. We compared the effects of the isoflavone daidzein, which has no action on tyrosine kinases, and 17β‐estradiol on the development and activity of osteoclasts in vitro. Nonadherent porcine bone marrow cells were cultured on dentine slices or on culture slides in the presence of 10 −8 M of 1,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ], with or without 10 −8 M of daidzein, 10 −8 M of 17β‐estradiol for 9‐11 days. Multinucleated tartrate‐resistant acid phosphatase‐positive (TRAP + ) cells that resorbed bone (osteoclasts) developed in the presence of 1,25(OH) 2 D 3 . The number of osteoclasts formed in response to 1,25(OH) 2 D 3 was reduced by 58 ± 8% by daidzein and 52 ± 5% by estrogen ( p < 0.01); these effects were reversed by 10 −6 M of ICI 182,780. The area resorbed by mature osteoclasts was reduced by 39 ± 5% by daidzein and 42 ± 6% by estradiol ( p < 0.01). Both compounds also inhibited the 1,25(OH) 2 D 3 ‐induced differentiation of osteoclast progenitors (mononucleated TRAP + cells), 53 ± 8% by daidzein and 50 ± 7% by estradiol ( p < 0.05). Moreover, daidzein and estradiol promoted caspase‐8 and caspase‐3 cleavage and DNA fragmentation of monocytic bone marrow cells. Caspase‐3 cleavage was reversed by 10 −8 M of ICI 182,780. Both compounds up‐regulated the expression of nuclear estrogen receptors ER‐α and ER‐β. Thus, daidzein, at the same concentration as 17β‐estradiol, inhibits osteoclast differentiation and activity. This may be caused by, at least in part, greater apoptosis of osteoclast progenitors mediated by ERs.