Hindlimb-unloading suppresses B cell population in the bone marrow and peripheral circulation associated with OPN expression in circulating blood cells.
Hindlimb-unloading suppresses B cell population in the bone marrow and peripheral circulation associated with OPN expression in circulating blood cells.
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后肢卸载抑制了骨髓和外周循环中与循环血细胞中 OPN 表达相关的 B 细胞群。
DOI：
10.1007/s00774-014-0568-8
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Noda M.
中科院分区：
文献类型：
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作者：
Ezura Y1;Nagata J;Nagao M;Hemmi H;Hayata T;Rittling S;Denhardt DT;Noda M.
尾部悬吊的啮齿动物后肢去负荷（HU）是研究废用性骨丢失的动物模型。以前，我们已经证明骨桥蛋白（OPN，也称为Spp 1）是卸载诱导的骨丢失所必需的。然而，卸载如何影响OPN在体内的表达尚未完全了解。在这里，我们研究了骨桥蛋白表达在外周血中的小鼠受到HU。实时荧光定量RT-PCR分析表明，OPN在循环外周血细胞中的表达增加。这种HU诱导的OPN mRNA表达的增加在循环外周血细胞中是特异性的，因为OPN在骨髓中的血细胞中没有增加。HU诱导的外周血细胞中OPN表达的增强与外周血中单核细胞/巨噬细胞谱系细胞分数的增加相关。相反，HU降低外周血中B淋巴细胞的分数大小。我们进一步研究了B淋巴细胞生成是否在骨桥蛋白缺陷的小鼠中受到HU的影响。在骨髓中，HU显著降低B淋巴细胞谱系细胞的数量，而不改变单核细胞/巨噬细胞谱系细胞的数量。胡萝卜素还能增加骨髓中T淋巴细胞的数量。有趣的是，这些变化在OPN缺陷型和野生型小鼠中观察到相似。这些结果首次表明HU增加循环细胞中OPN的表达并抑制骨髓B淋巴细胞生成。
Rodent hindlimb unloading (HU) by tail-suspension is a model to investigate disuse-induced bone loss in vivo. Previously, we have shown that osteopontin (OPN, also known as Spp1) is required for unloading-induced bone loss. However, how unloading affects OPN expression in the body is not fully understood. Here, we examined OPN expression in peripheral blood of mice subjected to HU. Real-time RT-PCR analysis indicated that OPN expression is increased in circulating peripheral blood cells. This HU-induced increase in OPN mRNA expression was specific in circulating peripheral blood cells, as OPN was not increased in the blood cells in bone marrow. HU-induced enhancement in OPN expression in peripheral blood cells was associated with an increase in the fraction of monocyte/macrophage lineage cells in the peripheral blood. In contrast, HU decreased the fraction size of B-lymphocytes in the peripheral blood. We further examined if B-lymphogenesis is affected in the mice deficient for osteopontin subjected to HU. In bone marrow, HU decreased the population of the B-lymphocyte lineage cells significantly, whereas it did not alter the population of monocyte/macrophage lineage cells. HU also increased the cells in T-lymphocyte lineage in bone marrow. Interestingly, these changes were observed similarly both in OPN-deficient and wild-type mice. These results indicate for the first time that HU increases OPN expression in circulating cells and suppresses bone marrow B-lymphogenesis.