Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing, China.
Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing, China.
Cell Biochem Funct. 2018 Apr;36(3):155-165. doi: 10.1002/cbf.3327. Epub 2018 Feb 13.
Severe hypoxia inhibits the adhesion and mobility of bone marrow-derived mesenchymal stem cells (BMSCs) and limits their application in bone tissue engineering. In this study, CoCl was used to simulate severe hypoxia and the effects of mechano-growth factor (MGF) E peptide on the morphology, adhesion, migration, and proangiogenic capacity of BMSCs under hypoxia were measured. It was demonstrated that severe hypoxia (500-μM CoCl ) significantly caused cell contraction and reduced cell area, roundness, adhesion, and migration of BMSCs. RhoA and ROCK1 expression levels were upregulated by severe hypoxia, but p-RhoA and mobility-relevant protein (integrin β1, p-FAK and fibronectin) expression levels in BMSCs were inhibited. Fortunately, MGF E peptide could restore all abovementioned indexes except RhoA expression. MEK-ERK1/2 pathway was involved in MGF E peptide regulating cell morphological changes, mobility, and relevant proteins (except p-FAK). PI3K-Akt pathway was involved in MGF E peptide regulating cell area, mobility, and relevant proteins. Besides, severe hypoxia upregulated vascular endothelial growth factor α expression but was harmful for proangiogenic capacity of BMSCs. Our study suggested that MGF E peptide might be helpful for the clinical application of tissue engineering strategy in bone defect repair.
Sever hypoxia impairs bone defect repair with bone marrow-derived mesenchymal stem cells (BMSCs). This study proved that mechano-growth factor E (MGF E) peptide could improve the severe hypoxia-induced cell contraction and decline of cell adhesion and migration of BMSCs. Besides, MGF E peptide weakened the effects of severe hypoxia on the cytoskeleton arrangement- and mobility-relevant protein expression levels in BMSCs. The underlying molecular mechanism was also verified. Finally, it was confirmed that MGF E peptide showed an adverse effect on the expression level of vascular endothelial growth factor α in BMSCs under severe hypoxia but could make up for this deficiency through accelerating cell proliferation.
严重缺氧会抑制骨髓间充质干细胞（BMSCs）的黏附和迁移，限制其在骨组织工程中的应用。在本研究中，使用 CoCl2 模拟严重缺氧，并测量机械生长因子（MGF）E 肽对缺氧下 BMSCs 形态、黏附、迁移和促血管生成能力的影响。结果表明，严重缺氧（500μM CoCl2）显著导致细胞收缩，减少细胞面积、圆度、黏附性和迁移能力。RhoA 和 ROCK1 的表达水平上调，但严重缺氧抑制了 BMSCs 中迁移相关蛋白（整合素β1、p-FAK 和纤维连接蛋白）的表达。幸运的是，MGF E 肽可以恢复除 RhoA 表达之外的所有上述指标。MEK-ERK1/2 通路参与了 MGF E 肽调节细胞形态变化、迁移和相关蛋白（除了 p-FAK）的表达。PI3K-Akt 通路参与了 MGF E 肽调节细胞面积、迁移和相关蛋白的表达。此外，严重缺氧上调血管内皮生长因子α的表达，但对 BMSCs 的促血管生成能力有害。本研究表明，MGF E 肽可能有助于组织工程策略在骨缺损修复中的临床应用。
严重缺氧会损害骨髓间充质干细胞（BMSCs）修复骨缺损的能力。本研究证明，机械生长因子 E（MGF E）肽可改善严重缺氧引起的细胞收缩以及 BMSCs 黏附和迁移能力下降。此外，MGF E 肽减弱了严重缺氧对 BMSCs 细胞骨架排列和迁移相关蛋白表达水平的影响。其潜在的分子机制也得到了验证。最后，证实 MGF E 肽在严重缺氧下对 BMSCs 中血管内皮生长因子α的表达水平有不良影响，但通过加速细胞增殖可以弥补这一不足。
