Genistein prevents bone resorption diseases by inhibiting bone resorption and stimulating bone formation.
Genistein, a soybean-derived isoflavone, has been shown to suppress osteoclastic bone resorption. To clarify the mechanisms underlying this action, we investigated the effects of genistein on the differentiation, cytoskeleton and function in mice osteoclasts in vitro and bone metabolism in ovariectomized rats.


METHODS
Primary OCs were isolated from 3 week-old mice and induced by 1,25(OH)(2)D(3). Then OCs were exposed to genistein at various concentration of 0 M, 10(-9) M, 10(-8) M, 10(-7) M, 10(-6) M, and 10(-5) M. The number of TRAP+ cells were counted as well as the surface area of bone resorption on bone slice. F-actin change was observed by Confocal. In vivo, forty 12 week-old female SD rats were randomly assigned to four groups: (1) sham operated (Sham); (2) (OVX); (3) ovariectomized and treated with estradiol (OVX-E); (4) ovariectomized and received genistein (OVX-G). After 12 weeks, BMD, body weight, serum level of alkaline phosphatase (ALP), acid phosphatase (ACP), osteocalcin (OC), IL-1beta, TNFalpha, IL-6 and calcitonin (CT) were evaluated. Femur were sectioned. In addition, the serum estradiol, the weight of uteri and histological behavior were also examined to indicate the side effect of genistein to the uteri.


RESULTS
In vitro, the number of TRAP+ cells decreased depending on the concentration of genistein as well as the area of bone resorption. F-actin became disorder under Confocal. In vivo, after treated with genistein, BMD and the serum level of ALP, ACP, osteocalcin increased significantly, while the serum level of IL-1beta and TNFalpha decreased. Especially, the increase of ALP and osteocalcin of OVX-G was higher than that of OVX-E. Histologically, the pachy-trabecula were observed as well as the more mineral deposition lines. Additionally, the uterus weight index and the serum estradiol in OVX-G rats were lower significantly than those of OVX-E. The epithelia of uteri gland in OVX-G appeared cubic while those of OVX-E became squamous.


CONCLUSIONS
Genistein can prevent bone resorption diseases by the promotion of bone formation and the prevention of bone resorption with slight side effect.
Li
Binbin
B
Department of Oral Pathology, Peking University School of Stomatology, 22 South Zhongguancun Avenue, Haidian District, Beijing 100081, P.R. China. kqlibinbin@yahoo.com.cn
Yu
Shifeng
S
D015502:Absorptiometry, Photon; D000199:Actins / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000473:pathology / Q000517:prevention & control*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D005269:Femur / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D066298:In Vitro Techniques; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D009929:Organ Size / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000166:cytology / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000473:pathology
D000199:Actins; D004958:Estradiol; D019833:Genistein