Roles of plasminogen in the alterations in bone marrow hematopoietic stem cells during bone repair.
Roles of plasminogen in the alterations in bone marrow hematopoietic stem cells during bone repair.
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DOI：
10.1016/j.bonr.2018.04.005
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发表时间：
2018-06
期刊：
影响因子：
2.5
通讯作者：
Kaji H
中科院分区：
文献类型：
--
作者：
Okada K;Kawao N;Tatsumi K;Ishida M;Takafuji Y;Kurashimo S;Okumoto K;Kojima K;Matsuo O;Kaji H
我们以前发现，基质细胞衍生因子-1（SDF-1）参与了小鼠骨修复过程中骨髓干细胞数量的变化。此外，我们报道了纤溶酶原（Plg）缺乏延迟骨修复和巨噬细胞在小鼠骨损伤部位的积累。我们研究了Plg在骨修复过程中骨髓干细胞变化中的作用。我们用流式细胞术分析了Plg缺陷和野生型小鼠股骨损伤后骨髓中造血干细胞（HSC）和间充质干细胞（MSC）的数量。Plg缺乏显著减弱了小鼠骨损伤后HSC数量的减少，尽管它不影响MSC数量的增加。Plg缺乏可显著降低骨损伤周围骨内膜中SDF-1和Osterix或SDF-1和碱性磷酸酶双阳性细胞的数量以及骨损伤引起的基质金属蛋白酶-9（MMP-9）活性和SDF-1和转化生长因子-β（TGF-β）mRNA水平。TGF-β信号传导抑制显著减弱了骨损伤后HSC数量的减少。目前的研究表明，Plg通过MMP-9、TGF-β和SDF-1在小鼠骨修复过程中损伤部位对骨髓HSC的变化至关重要。我们研究了纤溶酶原在小鼠骨损伤后骨髓干细胞变化中的作用。纤维蛋白溶酶原缺乏使骨损伤后HSC数量的减少变钝。纤溶酶原缺乏可抑制损伤部位SDF-1、TGF-β和MMP-9的表达。TGF-β信号传导抑制使骨损伤后HSC数量的减少变钝。纤溶酶原通过TGF-β和SDF-1参与骨修复过程中损伤部位的HSC变化。
We previously revealed that stromal cell-derived factor-1 (SDF-1) is involved in the changes in the number of bone marrow stem cells during the bone repair process in mice. Moreover, we reported that plasminogen (Plg) deficiency delays bone repair and the accumulation of macrophages at the site of bone damage in mice. We investigated the roles of Plg in the changes in bone marrow stem cells during bone repair. We analyzed the numbers of hematopoietic stem cells (HSC) and mesenchymal stem cells (MSCs) within bone marrow from Plg-deficient and wild-type mice after a femoral bone injury using flow cytometric analysis. Plg deficiency significantly blunted a decrease in the number of HSCs after bone injury in mice, although it did not affect an increase in the number of MSCs. Plg deficiency significantly blunted the number of SDF-1- and Osterix- or SDF-1- and alkaline phosphatase-double-positive cells in the endosteum around the lesion as well as matrix metalloprotainase-9 (MMP-9) activity and mRNA levels of SDF-1 and transforming growth factor–β (TGF-β) elevated by bone injury. TGF-β signaling inhibition significantly blunted a decrease in the number of HSCs after bone injury. The present study showed that Plg is critical for the changes in bone marrow HSCs through MMP-9, TGF-β, and SDF-1 at the damaged site during bone repair in mice. We investigated the roles of plasminogen in bone marrow stem cell changes after bone injury in mice. Plasminogen deficiency blunted a decrease in the number of HSCs after bone injury. Plasminogen deficiency blunted the expression of SDF-1, TGF-β and MMP-9 at the damaged site. TGF-β signaling inhibition blunted a decrease in the number of HSCs after bone injury. Plasminogen is involved in HSC change through TGF-β and SDF-1 at the damaged site during bone repair.