Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function: Similarity to estrogen deficiency
Increased B-lymphopoiesis by interleukin 7 induces bone loss in mice with intact ovarian function: Similarity to estrogen deficiency
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DOI：
10.1073/pnas.94.17.9360
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发表时间：
1997-08-19
影响因子：
11.1
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Miyaura, C;Onoe, Y;Suda, T
由卵巢切除术（OVX）引起的雌激素缺乏会导致破骨细胞刺激骨吸收引起的显著骨丢失。在我们对雌激素缺乏引起骨丢失的发病机制的研究中，我们发现OVX选择性地刺激B淋巴细胞生成，导致B220阳性前B细胞在小鼠骨髓中显著积聚。为了研究刺激的R-淋巴细胞生成和骨丢失之间可能的相关性，用白细胞介素（IL）7治疗8周龄的雌性小鼠，其刺激骨髓中的B-淋巴细胞生成。我们还检查了IL-7受体敲除小鼠的骨量，这些小鼠表现出骨髓中B淋巴细胞生成的显著抑制。在卵巢功能完整的小鼠中，IL-7给药诱导的B淋巴细胞生成增加通过刺激骨细胞骨吸收导致显著的骨丢失。IL-7处理的雌性小鼠B淋巴细胞生成和骨质量的变化与年龄匹配的OVX小鼠相似。相反，与相应的野生型和杂合子同窝仔相比，雌性和雄性IL-7受体敲除小鼠的股骨骨小梁体积均显著增加。这些结果表明，骨髓B淋巴细胞生成的紊乱与骨量的变化密切相关。我们认为，雌激素缺乏引起的B淋巴细胞生成增加参与了骨吸收的机制。
Estrogen deficiency caused by ovariectomy (OVX) results in a marked bone loss due to stimulated bone resorption by osteoclasts. During our investigations of the pathogenesis of bone loss in estrogens deficiency, we found that OVX selectively stimulates B-lymphopoiesis which results in marked accumulation of B220-positire pre-B cells in mouse bone marrow. To examine the possible correlation between stimulated R-lymphopoiesis and bone loss, 8-week-old female mice were treated with interleukin (IL) 7, which stimulates B-lymphopoiesis in bone marrow. We also examined bone mass in IL-7 receptor-knockout mice that exhibit marked suppression of B-lymphopoiesis in the bone marrow, The increased B-lymphopoiesis induced by IL-7 administration resulted in marked bone loss by stimulation of osteoclastic bone resorption in mice with intact ovarian function. The changes in both B-lymphopoiesis and hone mass in IL-7-treated female mice were similar to those in age-matched OVX mice, In contrast, the trabecular bone volume of the femur was greatly increased in both female and male IL-7 receptor-knockout mice when compared with the respective wild-type and heterozygous littermates. These results show that the perturbation of B-lymphopoiesis in the bone marrow is closely linked to the change in bone mass, We propose here that the Increased B-lymphopoiesis due to estrogen deficiency is in volved in the mechanism of stimulated bone resorption.