Pathogenesis of bone loss due to estrogen deficiency : Relationship between increased B-lymphopoiesis and bone resorption.

由卵巢切除术（OVX）引起的雌激素缺乏导致由于刺激的骨细胞骨吸收而引起的显著骨丢失。最近的研究表明，骨吸收细胞因子如白细胞介素（IL）-1，IL-6和肿瘤坏死因子α可能参与了雌激素缺乏引起的骨丢失，在本研究中，我们发现OVX选择性地刺激B淋巴细胞生成，导致前B细胞在小鼠骨髓中显著积聚。与雌激素缺乏一样，雄激素缺乏也会在骨质流失前刺激小鼠骨髓中的B淋巴细胞生成。为了检查受刺激的B淋巴细胞生成和骨丢失之间的可能关系，用IL-7处理雌性小鼠，其刺激骨髓中的B淋巴细胞生成。在卵巢功能完整的小鼠中，IL-7诱导的B淋巴细胞生成增加通过刺激骨吸收而导致显著的骨丢失。通过骨矿物质密度（BMD）和muCT分析测量，骨丢失的程度与OVX小鼠相似。在IL-7受体敲除小鼠中检测到更高的骨量，其中B淋巴细胞生成显著减少。本研究结果表明，骨髓B淋巴细胞生成的紊乱与骨量的变化密切相关。性类固醇缺乏引起的B淋巴细胞生成增加可能参与了刺激骨吸收的机制。

Estrogen deficiency caused by ovariectomy (OVX) results in a marked bone loss due to stimulated osteoclastic bone resorption. Recent studies indicated the possible involvement of bone-resorbing cytokines such as interleukin (lL) -1, IL-6 and tumor necrosis factor alpha in bone loss due to estrogen deficiency.In this study, we found that OVX selectively stimulated B-lymphopoiesis which resulted in a marked accumulation of pre-B cells in mouse bone marrow. Like estrogen deficiency, androgen deficiency also stimulated B-lymphopoiesis in mouse bone marrow prior to bone loss. To examine the possible relationship between stimulated B-lymphopoiesis and bone loss, female mice were treated with IL-7, which stimulates B-lymphopoiesis in bone marrow. The increased B-lymphopoiesis induced by IL-7 resulted in a marked bone loss by stimulating bone resorption in mice with intact ovarian function. The extent of bone loss was similar to that in OVX mice, measured by bone mineral density (BMD) and muCT analysis. A higher bone mass was detected in IL-7 receptor-knockout mice in which B-lymphopoiesis was markedly reduced. The results obtained in this stuby show that the perturbation of B-lymphopoiesis in bone marrow is closely linked to the change in bone mass. Increased B-lymphopoiesis due to sex steroid deficiency may be involved in the mechanism of stimulated bone resorption.