Osteoblastic N-cadherin is not required for microenvironmental support and regulation of hematopoietic stem and progenitor cells
Osteoblastic N-cadherin is not required for microenvironmental support and regulation of hematopoietic stem and progenitor cells
复制标题
DOI：
10.1182/blood-2011-09-377853
复制
发表时间：
2012-07-12
期刊：
影响因子：
20.3
通讯作者：
Calvi, Laura M.
中科院分区：
文献类型：
--
作者：
Bromberg, Olga;Frisch, Benjamin J.;Calvi, Laura M.
造血干细胞(HSC)的调节高度依赖于与骨髓微环境的相互作用。N-钙粘附素在支持造血干细胞中的作用存在争议。具体地说，目前尚不清楚正常骨髓微结构和造血是否需要微环境N-钙粘附素。为了确定成骨细胞N-钙粘素是否是HSC调节所必需的，我们使用了一种遗传小鼠模型，在该模型中，N-钙粘蛋白编码基因CDH2的缺失针对成骨细胞系的细胞。靶向缺失N-钙粘附素导致年龄依赖性的骨表型，最终特征是矿化骨减少，但在任何时间测试的稳态HSC数量或功能没有差异，并从清髓性损伤中正常恢复。间歇性甲状旁腺激素(PTH)治疗是公认的对骨的合成代谢，并通过微环境相互作用增加骨髓HSCs。缺乏成骨细胞N-钙粘素不会阻断甲状旁腺激素治疗的骨合成代谢或HSC效应。这份报告表明，成骨细胞N-钙粘附素不是调节稳态造血、造血干细胞对骨髓消融的反应所必需的，也不是通过间歇甲状旁腺素治疗来快速扩增造血干细胞所必需的。(血。2012；120(2)：303-313)
Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with the marrow microenvironment. Controversy exists on N-cadherin's role in support of HSCs. Specifically, it is unknown whether microenvironmental N-cadherin is required for normal marrow microarchitecture and for hematopoiesis. To determine whether osteoblastic N-cadherin is required for HSC regulation, we used a genetic murine model in which deletion of Cdh2, the gene encoding N-cadherin, has been targeted to cells of the osteoblastic lineage. Targeted deletion of N-cadherin resulted in an age-dependent bone phenotype, ultimately characterized by decreased mineralized bone, but no difference in steady-state HSC numbers or function at any time tested, and normal recovery from myeloablative injury. Intermittent parathyroid hormone (PTH) treatment is well established as anabolic to bone and to increase marrow HSCs through microenvironmental interactions. Lack of osteoblastic N-cadherin did not block the bone anabolic or the HSC effects of PTH treatment. This report demonstrates that osteoblastic N-cadherin is not required for regulation of steady-state hematopoiesis, HSC response to myeloablation, or for rapid expansion of HSCs through intermittent treatment with PTH. (Blood. 2012;120(2):303-313)