Inhibitory effect of genistein on osteoclast-like cell formation in mouse marrow cultures

The effect of genistein on osteoclast-like cell formation in mouse marrow culture in vitro was investigated. The bone marrow cells were cultured for 7 days in alpha-minimal essential medium containing a well-known bone resorbing agent [parathyroid hormone (1-34) (PTH), prostaglandin E2 (PGE2), 1,25 dihydroxyvitamin D3 (VD3), or lipopolysaccharide (LPS)] with an effective concentration. Osteoclast-like cell formation was estimated by staining for tartrate-resistant acid phosphatase (TRACP), a marker enzyme of osteoclasts. The presence of PTH (10(-8) M), PGE2 (10(-6) M), VD3 (10(-8) M), or LPS (1 microg/mL) induced a remarkable increase in osteoclast-like multinucleated cells. These increases were inhibited significantly in the presence of genistein (10(-7) to 10(-5) M). The inhibitory effect of genistein (10(-5) M) was equal to that of 17 beta-estradiol (10(-8) M), calcitonin (10(-9) M), or zinc sulfate (10(-5) M). Genistein (10(-5) M) significantly inhibited dibutyryl cyclic adenosine monophosphate (10(-5) M)-induced osteoclast-like cell formation. However, genistein (10(-5) M) did not inhibit phorbol 12-myristate 13-acetate-induced osteoclast-like cell formation. The present study demonstrated that genistein has a potent inhibitory effect on osteoclast-like cell formation in mouse marrow culture. The inhibitory action of genistein may involve in cyclic AMP signaling.