Suppressive Effect of Genistein on Rat Bone Osteoclasts : Apoptosis Is Induced through Ca2+ Signaling

• Published in: Biological & pharmaceutical bulletin 1999/08/15, Vol.22(8), pp.805-809
• Main Authors: GAO, Ying Hua, YAMAGUCHI, Masayoshi
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Biological and medical sciences; Bone and Bones - cytology; Bone and Bones - drug effects; Bone and Bones - metabolism; calcitonin; calcium; Calcium Signaling; Cattle; Cells, Cultured; daidzein; Fundamental and applied biological sciences. Psychology; General pharmacology; genistein; Genistein - pharmacology; Isoflavones - pharmacology; Male; Medical sciences; osteoclast; Osteoclasts - drug effects; Osteoclasts - metabolism; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Rats; Rats, Wistar; Skeleton and joints; Space life sciences; Tamoxifen - pharmacology; Vertebrates: osteoarticular system, musculoskeletal system
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.22.805

The effect of genistein on osteoclase-like multinucleated cells (MNCs) from rat femoral tissues was investigated. When rat marrow cells were cultured for 7 d in a medium containing either vehicle, parathyroid hormone (10-8 M) or prostaglandine E2 (10-6 M), the formation of tartrate-resistant acid phosphatase (TRACP)-positive MNCs was significantly increased. This increase was markedly weakened by the presence of genistein (10-6 or 10-5 M). The bone cells isolated from rat femoral tissues were cultured for 48 h in an α-minimal essential medium (5% fetal bovine serum) containing either vehicle or genistein (10-8 to 10-5 M). Osteoclasts were estimated by staining for TRACP, a marker enzyme of osteoclasts. The presence of genistein caused a significant decrease in the number of osteoclasts. Such a decrease was also seen in the presence of calcitonin (10-10 to 10-8 M), dibutyryl cyclic adenosine 5'-monophosphate (DcAMP; 10-6 and 10-5 M), calcium chloride (10-4 and 10-3 M) or daidzein (10-7 to 10-5 M). The suppressive effect of genistein (10-5 M) was not further enhanced in the presence of calcitonin (10-8 M), DcAMP (10-5 M), or calcium chloride (10-3 M), and was completely abolished by the presence of dibucaine (10-6 M) or staurosporine (10-7 M), both of which are inhibitors of Ca2+-dependent protein kinases. Ca2+ ionophore (A23187; 10-6 M) induced a remarkable decrease in the number of osteoclasts in the absence or presence of genistein (10-5 M) or calcium chloride (10-3 M). The present study demonstrates that genistein has a direct suppressive effect on osteoclasts in vitro, suggesting that the isoflavone may induce apoptosis which is mediated through the pathway of intracellular Ca2+ signaling.