Molecular mechanisms of osteoporosis induced by estrogen deficiency.

1.雌激素缺乏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部分中存在的骨吸收活性。在小鼠长骨器官培养中加入20-80%的骨髓上清液，剂量依赖性地刺激骨吸收。抗il - α抗体完全中和OVX小鼠骨髓上清液中的骨吸收活性。针对il - β、IL-6和IL-6受体的抗体也能部分中和它。同时加入IL-1、IL-6和可溶性IL-6受体，其浓度相当于OVX小鼠骨髓上清液的内源性浓度，共同诱导骨吸收。这些结果表明，雌激素缺乏时骨吸收的增强是由多种因素而不是单一因素引起的。性类固醇缺乏症患者造血功能增加。OVX引起的雌激素缺乏选择性地刺激B淋巴生成，导致小鼠骨髓中前B细胞显著积累。我们比较了雌激素和雄激素对去兰科（ORX）小鼠骨髓B淋巴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，增加的细胞多为b220阳性的前b淋巴细胞。术后受刺激的B淋巴细胞积累的细胞特征和变化的时间过程与OVX小鼠非常相似。这些由ORX引起的造血和骨代谢的变化通过雌激素的治疗完全恢复。这些结果表明，雌激素不仅对雌性小鼠，而且对雄性小鼠的B淋巴细胞生成和骨代谢有调节作用。

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.