金雀异黄素通过抑制骨吸收和刺激骨形成来预防骨吸收疾病。

Genistein prevents bone resorption diseases by inhibiting bone resorption and stimulating bone formation.

作者信息

Li Binbin, Yu Shifeng

机构信息

Department of Oral Pathology, Peking University School of Stomatology, 22 South Zhongguancun Avenue, Haidian District, Beijing 100081, P.R. China.

出版信息

Biol Pharm Bull. 2003 Jun;26(6):780-6. doi: 10.1248/bpb.26.780.

DOI:10.1248/bpb.26.780

PMID:12808286

Abstract

UNLABELLED

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.

STUDY DESIGN

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.

摘要

未标记

染料木黄酮是一种源自大豆的异黄酮，已被证明可抑制破骨细胞的骨吸收。为阐明此作用的潜在机制，我们研究了染料木黄酮对体外培养的小鼠破骨细胞分化、细胞骨架和功能以及对去卵巢大鼠骨代谢的影响。

研究设计

从3周龄小鼠中分离出原代破骨细胞，并由1,25(OH)₂D₃诱导。然后将破骨细胞暴露于浓度分别为0 M、10⁻⁹ M、10⁻⁸ M、10⁻⁷ M、10⁻⁶ M和10⁻⁵ M的染料木黄酮中。计数抗酒石酸酸性磷酸酶（TRAP）阳性细胞数量以及骨切片上的骨吸收表面积。通过共聚焦显微镜观察F-肌动蛋白的变化。在体内，将40只12周龄雌性SD大鼠随机分为四组：（1）假手术组（Sham）；（2）去卵巢组（OVX）；（3）去卵巢并接受雌二醇治疗组（OVX-E）；（4）去卵巢并接受染料木黄酮治疗组（OVX-G）。12周后，评估骨密度、体重、血清碱性磷酸酶（ALP）、酸性磷酸酶（ACP）、骨钙素（OC）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNFα）、白细胞介素-6（IL-6）和降钙素（CT）水平。取股骨切片。此外，还检测血清雌二醇、子宫重量以及组织学表现，以表明染料木黄酮对子宫的副作用。

结果

在体外，TRAP阳性细胞数量随染料木黄酮浓度的增加而减少，骨吸收面积也减小。共聚焦显微镜下观察到F-肌动蛋白变得紊乱。在体内，用染料木黄酮治疗后，骨密度以及血清ALP、ACP、骨钙素水平显著升高，而血清IL-1β和TNFα水平降低。特别是，OVX-G组的ALP和骨钙素升高幅度高于OVX-E组。组织学上，观察到骨小梁增厚以及更多的矿化沉积线。此外，OVX-G组大鼠的子宫重量指数和血清雌二醇水平显著低于OVX-E组。OVX-G组子宫腺上皮呈立方状，而OVX-E组则变为鳞状。