Negative pressure wound therapy promotes muscle-derived stem cell osteogenic differentiation through MAPK pathway.

Negative pressure wound therapy promotes muscle-derived stem cell osteogenic differentiation through MAPK pathway.
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负压伤口治疗通过MAPK途径促进肌源性干细胞成骨分化。

DOI:
10.1111/jcmm.13339
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发表时间:
2018-01
影响因子:
5.3
通讯作者:
Yu A
Yu A
中科院分区:
医学2区
文献类型:
--
作者:
Liu H;Zheng X;Chen L;Jian C;Hu X;Zhao Y;Li Z;Yu A

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负压伤口治疗(NPWT)已被证实可有效治疗开放性骨折,但其潜在机制尚不清楚。本文旨在研究负压伤口治疗(NPWT)对肌源性干细胞(MDSC)成骨细胞分化的影响及其相关潜在机制。与3天静态组相比,NPWT处理MDSC的细胞增殖率大幅增加。与对照组相比,NPWT处理3天对MDSC的细胞凋亡无明显影响。NPWT组中HIF-1α、BMP-2、COL-I、OST和OPN的表达水平在第3、7和14天增加,但Runx 2的表达水平在第3和7天增加。处理前,将特异性抑制剂加入到NPWT处理的MDSC和对照组中。通过抑制ERK 1/2、p38和JNK通路,ALP活性和矿化降低。在第3、7和14天,使用特异性MAPK通路抑制剂也降低了Runx 2、COL-1、OST和OPN基因和蛋白的表达水平。除第3天外,对BMP-2的表达无显著影响。然而,当JNK通路被抑制时,HIF-1α基因和蛋白的表达略有增加。因此,NPWT通过MAPK通路促进MDSC的增殖和成骨分化。
Negative pressure wound therapy (NPWT) has been revealed to be effective in the treatment of open fractures, although the underlying mechanism is not clear. This article aimed to investigate the effects of NPWT on muscle‐derived stem cell (MDSC) osteoblastic differentiation and the related potential mechanism. The cell proliferation rate was substantially increased in NPWT‐treated MDSCs in comparison with a static group for 3 days. There was no observable effect on the apoptosis of MDSC treated with NPWT compared with the control group for 3 days. The expression levels of HIF‐1α, BMP‐2, COL‐I, OST and OPN were increased on days 3, 7 and 14, but the expression level of Runx2 was increased on days 3 and 7 in the NPWT group. Pre‐treatment, the specific inhibitors were added into the MDSCs treated with NPWT and the control group. ALP activity and mineralization were reduced by inhibiting the ERK1/2, p38 and JNK pathways. The expression levels of Runx2, COL‐I, OST and OPN genes and proteins were also decreased using the specific MAPK pathway inhibitors on days 3, 7 and 14. There were no significant effects on the expression of BMP‐2 except on day 3. However, the expressions of the HIF‐1α gene and protein slightly increased when the JNK pathway was inhibited. Therefore, NPWT promotes the proliferation and osteogenic differentiation of MDSCs through the MAPK pathway.
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