权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular mechanisms of osteoporosis induced by estrogen deficiency.

雌激素缺乏所致骨质疏松的分子机制。

基本信息

批准号：
06404067
负责人：
SUDA Tatsuo
金额：
$ 13.5万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

1.Endogenous bone-resorbing factors in estrogen deficiencyEstrogen deficiency causes a marked bone loss by stimulating osteoclastic bone resorption. In this study, we examined the bone-resorbing activity present in the supernatant fraction of mouse bone marrow collected from ovariectomized (OVX) mice. Adding bone marrow supernatants at 20-80% to organ cultures of mouse long bones dose-dependently stimulated bone resorption. Anti-IL-lalpha antibody completely neutralized the bone-resorbing activity present in bone marrow supernatants from OVX mice. Antibodies against IL-lbeta, IL-6 and IL-6 receptors also neutralized it, but partially. The concurrent addition of IL-1, IL-6 and soluble IL-6 receptor, which equaled the endogenous concentrations on bone marrow supernatants from OVX mice, co-operatively induced bone resorption. These results suggest that the enhanced bone resorption that occurs during estrogen deficiency is due to multi-factors rather than to a single factor.Increased hemopoiesis in sex steroid deficiency.Estrogen deficiency caused by OVX selectively stimulates B lymphopoiesis, resulting in a marked accumulation of pre-B cells in mouse bone marrow. We compared the effects of estrogen and androgen on B lymphopoiesis in bone marrow and bone metabolism using orchidectomised (ORX) mice. Some of the ORX mice were treated with estrogen or androgen. At3 weeks after operation, in ORX mice, the number of bone marrow cells were markedly increased, and most of the increased cells were B220-positive pre-B lymphocytes. The characteristics of the accumulated cells and the time course of changes of the stimulated B lymphopoiesis after operation were quite similar to those in OVX mice. These changes of hemopoiesis and bone metabolism induced by ORX were completely restored by the treatment of estrogen. These results suggest that estrogen regulates B lymphopoiesis and bone metabolism not only in female but also in male mice.

1.雌激素缺乏时的内源性骨吸收因子雌激素缺乏通过刺激破骨细胞骨吸收而导致明显的骨质流失。在这项研究中，我们检测了从卵巢切除 (OVX) 小鼠收集的小鼠骨髓上清液中存在的骨吸收活性。将 20-80% 的骨髓上清液添加到小鼠长骨的器官培养物中，剂量依赖性地刺激骨吸收。抗IL-1α抗体完全中和来自OVX小鼠的骨髓上清液中存在的骨吸收活性。针对IL-1β、IL-6和IL-6受体的抗体也能部分中和它。同时添加IL-1、IL-6和可溶性IL-6受体（等于OVX小鼠骨髓上清液中的内源浓度）协同诱导骨吸收。这些结果表明，雌激素缺乏时发生的骨吸收增强是多因素而非单一因素造成的。性类固醇缺乏时造血增加。OVX引起的雌激素缺乏选择性刺激B淋巴细胞生成，导致小鼠骨髓中前B细胞显着积累。我们使用睾丸切除 (ORX) 小鼠比较了雌激素和雄激素对骨髓 B 淋巴细胞生成和骨代谢的影响。一些 ORX 小鼠接受雌激素或雄激素治疗。术后3周，ORX小鼠骨髓细胞数量明显增加，增加的细胞大部分为B220阳性前B淋巴细胞。术后所积累的细胞特征以及受刺激的B淋巴细胞生成的变化时间进程与OVX小鼠非常相似。 ORX引起的这些造血和骨代谢的变化在雌激素治疗后完全恢复。这些结果表明，雌激素不仅可以调节雌性小鼠的 B 淋巴细胞生成和骨代谢，还可以调节雄性小鼠的 B 淋巴细胞生成和骨代谢。