Matrix-Embedded Osteocytes Regulate Mobilization of Hematopoietic Stem/Progenitor Cells
Matrix-Embedded Osteocytes Regulate Mobilization of Hematopoietic Stem/Progenitor Cells
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DOI：
10.1016/j.stem.2013.05.001
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发表时间：
2013-06-06
期刊：
影响因子：
23.9
通讯作者：
Tanimoto, Mitsune
中科院分区：
文献类型：
--
作者：
Asada, Noboru;Katayama, Yoshio;Tanimoto, Mitsune
骨髓（BM）小生境包含调节造血干/祖细胞（HSPC）迁移出小生境并进入循环的多种细胞类型。在这里，我们证明了骨细胞，成熟骨的主要细胞成分，是HSPC出口的调节器。粒细胞集落刺激因子（G-CSF），临床上用于动员HSPC，诱导骨细胞网络的形态和基因表达的变化，先于成骨细胞的变化。这种快速反应可能是在交感神经系统的控制下，因为骨细胞表达β 2-肾上腺素能受体和外科交感神经切除术阻止它。骨细胞靶向消融或破坏骨细胞网络的小鼠在BM中有相当数量的HSPC，但未能动员HSPC响应G-CSF。综上所述，这些结果表明，BM/骨生态位界面是从骨基质内部严格控制的，并确立了骨骼组织在造血功能中的重要生理作用。
The bone marrow (BM) niche comprises multiple cell types that regulate hematopoietic stem/progenitor cell (HSPC) migration out of the niche and into the circulation. Here, we demonstrate that osteocytes, the major cellular component of mature bone, are regulators of HSPC egress. Granulocyte colony-stimulating factor (G-CSF), used clinically to mobilize HSPCs, induces changes in the morphology and gene expression of the osteocytic network that precedes changes in osteoblasts. This rapid response is likely under control of the sympathetic nervous system, since osteocytes express the b2-adrenergic receptor and surgical sympathectomy prevents it. Mice with targeted ablation of osteocytes or a disrupted osteocyte network have comparable numbers of HSPCs in the BM but fail to mobilize HSPCs in response to G-CSF. Taken together, these results indicate that the BM/bone niche interface is critically controlled from inside of the bone matrix and establish an important physiological role for skeletal tissues in hematopoietic function.