G-CSF increases mesenchymal precursor cell numbers in the bone marrow via an indirect mechanism involving osteoclast-mediated bone resorption
G-CSF increases mesenchymal precursor cell numbers in the bone marrow via an indirect mechanism involving osteoclast-mediated bone resorption
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DOI：
10.1016/j.scr.2010.04.002
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发表时间：
2010-07-01
影响因子：
1.2
通讯作者：
Simmons, Paul J.
中科院分区：
文献类型：
--
作者：
Brouard, Nathalie;Driessen, Rebecca;Simmons, Paul J.
在研究 MPC 循环是否响应 G-CSF（最常用于诱导造血祖细胞动员的药物）的过程中，我们观察到，虽然 G-CSF 未能增加循环中 MPC 的数量（体外测定为成纤维细胞集落形成细胞，CFU-F），但 G-CSF 给药仍然导致造血祖细胞绝对数量呈时间依赖性增加。 BM 内的 CFU-F，在第 7 天达到峰值。用羟基脲处理 G-CSF 处理的小鼠的 BM 细胞并没有改变 CFU-F 数量，这表明 G-CSF 给药后 CFU-F 数量的增加并不是由于现有 CFU-F 的增殖。鉴于先前的研究表明 G-CSF 有效诱导小鼠骨转换，我们假设 CFU-F 的增加可能是由 G-CSF 给药后发生的骨吸收触发的。根据这一假设，给予破骨细胞分化抑制剂骨保护素（OPG）可阻止 G-CSF 诱导的 CFU-F 数量增加。总之，这些数据表明，常规用于动员造血干细胞的细胞因子治疗可以提供一种易于应用的方法来诱导 MPC 的体内扩增，用于临床应用。 (C) 2010 Elsevier B.V. 保留所有权利。
During the course of studies to investigate whether MPC circulate in response to G-CSF, the agent most frequently used to induce mobilization of hematopoietic progenitors, we observed that while G-CSF failed to increase the number of MPC in circulation (assayed in vitro as fibroblast colony-forming cells, CFU-F), G-CSF administration nevertheless resulted in a time-dependent increase in the absolute number of CFU-F within the BM, peaking at Day 7. Treatment of BM cells from G-CSF-treated mice with hydroxyurea did not alter CFU-F numbers, suggesting that the increase in their numbers in response to G-CSF administration is not due to proliferation of existing CFU-F. Given previous studies demonstrating that G-CSF potently induces bone turnover in mice, we hypothesized that the increase in CFU-F may be triggered by the bone resorption that occurs following G-CSF administration. In accord with this hypothesis, administration of an inhibitor of osteoclast differentiation, osteoprotegerin (OPG), prevented the increase of CFU-F numbers induced by G-CSF. In conclusion, these data indicate that the cytokine treatment routinely used to mobilize hematopoietic stem cells could provide a readily applicable method to induce in vivo expansion of MPC for clinical applications. (C) 2010 Elsevier B.V. All rights reserved.