Characterization of spontaneous bone marrow recovery after sublethal total body irradiation: importance of the osteoblastic/adipocytic balance.
Characterization of spontaneous bone marrow recovery after sublethal total body irradiation: importance of the osteoblastic/adipocytic balance.
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DOI：
10.1371/journal.pone.0030818
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Defresne MP
中科院分区：
文献类型：
--
作者：
Poncin G;Beaulieu A;Humblet C;Thiry A;Oda K;Boniver J;Defresne MP
许多研究已经研究了照射后的造血恢复，但对骨髓微环境的关注很少。尽管如此，先前在可逆性放射诱导的小鼠骨髓再生障碍性贫血模型中的研究表明，在造血再生之前，碱性磷酸酶(ALP)活性显着增加。碱性磷酸酶活性的增加不是由于细胞增殖，而是由于骨髓间充质干细胞(MSC)特性的改变。因此，我们开展了一项研究，以评估在接受亚致死剂量全身照射的小鼠中，与其造血支持能力相关的MSC进化的动力学。在我们的研究中，集落形成单位-成纤维细胞(CFU-Fs)实验显示，照射后的骨髓间充质干细胞比率显著增加。CFU-FS集落仍具有向间充质干细胞分化的能力，但照射后3d处死小鼠的集落显示出较高的碱性磷酸酶活性和成骨标志物表达的一过性增加，而PPAR、γ和NeuroPilin-1的表达则下降。CFU-Fs的造血支持能力也得到了改善：与对照组相比，照射后的CFU-Fs显著提高了造血祖细胞的增殖率，并加速了向粒系的分化。我们的数据首次证明了成骨细胞和脂肪细胞之间的平衡在自发骨髓再生中发挥的关键作用。首先，骨髓间充质干细胞向成骨细胞分化促进了造血祖细胞的增殖和粒细胞再生。然后，第二次(前)成骨细胞逐渐消失，取而代之的是脂肪细胞，脂肪细胞下调增殖和粒细胞分化，然后有助于恢复到照射前的条件。
Many studies have already examined the hematopoietic recovery after irradiation but paid with very little attention to the bone marrow microenvironment. Nonetheless previous studies in a murine model of reversible radio-induced bone marrow aplasia have shown a significant increase in alkaline phosphatase activity (ALP) prior to hematopoietic regeneration. This increase in ALP activity was not due to cell proliferation but could be attributed to modifications of the properties of mesenchymal stem cells (MSC). We thus undertook a study to assess the kinetics of the evolution of MSC correlated to their hematopoietic supportive capacities in mice treated with sub lethal total body irradiation. In our study, colony-forming units – fibroblasts (CFU-Fs) assay showed a significant MSC rate increase in irradiated bone marrows. CFU-Fs colonies still possessed differentiation capacities of MSC but colonies from mice sacrificed 3 days after irradiation displayed high rates of ALP activity and a transient increase in osteoblastic markers expression while pparγ and neuropilin-1 decreased. Hematopoietic supportive capacities of CFU-Fs were also modified: as compared to controls, irradiated CFU-Fs significantly increased the proliferation rate of hematopoietic precursors and accelerated the differentiation toward the granulocytic lineage. Our data provide the first evidence of the key role exerted by the balance between osteoblasts and adipocytes in spontaneous bone marrow regeneration. First, (pre)osteoblast differentiation from MSC stimulated hematopoietic precursor's proliferation and granulopoietic regeneration. Then, in a second time (pre)osteoblasts progressively disappeared in favour of adipocytic cells which down regulated the proliferation and granulocytic differentiation and then contributed to a return to pre-irradiation conditions.
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影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
6.5
作者：
Meirelles, LD;Nardi, NB
通讯作者：
Nardi, NB
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3.4
作者：
DILLY, SA;JAGGER, CJ;SLOANE, JP
通讯作者：
SLOANE, JP
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2.1
作者：
Bianco, Paolo;Sacchetti, Benedetto;Riminucci, Mara
通讯作者：
Riminucci, Mara
影响因子：
20.3
作者：
Dominici, Massimo;Rasini, Valeria;Horwitz, Edwin M.
通讯作者：
Horwitz, Edwin M.