Mechanical unloading of bone in microgravity reduces mesenchymal and hematopoietic stem cell-mediated tissue regeneration
Mechanical unloading of bone in microgravity reduces mesenchymal and hematopoietic stem cell-mediated tissue regeneration
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DOI：
10.1016/j.scr.2014.05.005
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发表时间：
2014-09-01
影响因子：
1.2
通讯作者：
Almeida, E. A. C.
中科院分区：
文献类型：
--
作者：
Blaber, E. A.;Dvorochkin, N.;Almeida, E. A. C.
哺乳动物组织的机械负载是组织生长和再生的有效促进剂，而微重力下的卸载可能会导致组织再生减少，可能是通过对干细胞组织祖细胞的影响。为了检验机械卸载改变骨髓间充质和造血干细胞谱系分化的具体假设，我们研究了小鼠股骨近端骨髓如何响应微重力下的卸载的细胞和分子方面。股骨头的小梁骨和皮质骨内膜骨表面在微重力下经历了显着的骨吸收，扩大了骨髓腔。从股骨头骨髓室分离的细胞显示早期间充质和造血分化的基因表达标记物显着下调，包括 FUT1(-6.72)、CSF2(-3.30)、CD90(-3.33)、PTPRC(-2.79) 和 GDF15(-2.45)，但不包括干细胞标记物，如 SOX2。在细胞水平上，原位组织学分析显示巨核细胞数量减少，而红细胞数量增加 2.33 倍。此外，红细胞显示出岩藻糖基化程度升高，并聚集在形成骨髓-血液屏障的鼻窦附近，这可能为解释航天贫血症提供了机制基础。微重力暴露后立即培养分离的骨髓细胞增加了骨髓祖细胞间充质分化为体外矿化骨结节和造血分化为破骨细胞的潜力，表明在微重力暴露期间未分化祖细胞的积累。这些结果支持这样的观点：微重力下哺乳动物组织的机械卸载是组织生长和再生机制的强抑制剂，作用于早期间充质和造血干细胞分化水平。由 Elsevier B.V. 出版
Mechanical loading of mammalian tissues is a potent promoter of tissue growth and regeneration, whilst unloading in microgravity can cause reduced tissue regeneration, possibly through effects on stem cell tissue progenitors. To test the specific hypothesis that mechanical unloading alters differentiation of bone marrow mesenchymal and hematopoietic stem cell lineages, we studied cellular and molecular aspects of how bone marrow in the mouse proximal femur responds to unloading in microgravity. Trabecular and cortical endosteal bone surfaces in the femoral head underwent significant bone resorption in microgravity, enlarging the marrow cavity. Cells isolated from the femoral head marrow compartment showed significant down-regulation of gene expression markers for early mesenchymal and hematopoietic differentiation, including FUT1(-6.72), CSF2(-3.30), CD90(-3.33), PTPRC(-2.79), and GDF15(-2.45), but not stem cell markers, such as SOX2. At the cellular level, in situ histological analysis revealed decreased megakaryocyte numbers whilst erythrocytes were increased 2.33 fold. Furthermore, erythrocytes displayed elevated fucosylation and clustering adjacent to sinuses forming the marrow-blood barrier, possibly providing a mechanistic basis for explaining spaceflight anemia. Culture of isolated bone marrow cells immediately after microgravity exposure increased the marrow progenitor's potential for mesenchymal differentiation into in-vitro mineralized bone nodules, and hematopoietic differentiation into osteoclasts, suggesting an accumulation of undifferentiated progenitors during exposure to microgravity. These results support the idea that mechanical unloading of mammalian tissues in microgravity is a strong inhibitor of tissue growth and regeneration mechanisms, acting at the level of early mesenchymal and hematopoietic stem cell differentiation. Published by Elsevier B. V.