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航天飞行暴露后骨髓间充质干细胞中神经系统发育基因的激活。

Activation of nervous system development genes in bone marrow derived mesenchymal stem cells following spaceflight exposure.

机构信息

Dipartimento di Oncologia, Biologia e Genetica, Universita' di Genova and Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.

出版信息

J Cell Biochem. 2010 Oct 1;111(2):442-52. doi: 10.1002/jcb.22765.

Abstract

Stalled cell division in precursor bone cells and reduced osteoblast function are considered responsible for the microgravity-induced bone loss observed during spaceflight. However, underlying molecular mechanisms remain unraveled. Having overcome technological difficulties associated with flying cells in a space mission, we present the first report on the behavior of the potentially osteogenic murine bone marrow stromal cells (BMSC) in a 3D culture system, flown inside the KUBIK aboard space mission ISS 12S (Soyuz TMA-8 + Increment 13) from March 30 to April 8, 2006 (experiment "Stroma-2"). Flight 1g control cultures were performed in a centrifuge located within the payload. Ground controls were maintained on Earth in another KUBIK payload and in Petri dishes. Half of the cultures were stimulated with osteo-inductive medium. Differences in total RNA extracted suggested that cell proliferation was inhibited in flight samples. Affymetrix technology revealed that 1,599 genes changed expression after spaceflight exposure. A decreased expression of cell-cycle genes confirmed the inhibition of cell proliferation in space. Unexpectedly, most of the modulated expression was found in genes related to various processes of neural development, neuron morphogenesis, transmission of nerve impulse and synapse, raising the question on the lineage restriction in BMSC.

摘要

细胞分裂停滞和前体细胞骨细胞中破骨细胞功能降低被认为是导致飞行中观察到的微重力性骨丢失的原因。然而,潜在的分子机制仍未被揭示。我们克服了在太空任务中飞行细胞相关的技术困难,首次报告了在三维培养系统中潜在成骨的鼠骨髓基质细胞(BMSC)的行为,该系统于 2006 年 3 月 30 日至 4 月 8 日在国际空间站 ISS 12S 号任务(联盟 TMA-8 +增量 13)的 KUBIK 内部飞行(实验“Stroma-2”)。1g 飞行对照培养物在位于有效载荷内的离心机中进行。地面对照在另一个 KUBIK 有效载荷和培养皿中在地球上进行。一半的培养物用成骨诱导培养基刺激。提取的总 RNA 差异表明,飞行样本中的细胞增殖受到抑制。Affymetrix 技术显示,1599 个基因在暴露于太空后改变了表达。细胞周期基因的表达降低证实了细胞在太空中增殖受到抑制。出乎意料的是,大多数调节表达的基因与各种神经发育、神经元形态发生、神经冲动和突触传递过程有关,这引发了关于 BMSC 谱系限制的问题。

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