ERK1/2 and Akt phosphorylation were essential for MGF E peptide regulating cell morphology and mobility but not proangiogenic capacity of BMSCs under severe hypoxia.
Sha. Yongqiang Y; Yang. Li L; Lv. Yonggang Y
Key Findings
- Severe hypoxia (simulated with CoCl2) makes BMSCs shrink, become less round, and reduces their adhesion and migration.
- Adding MGF‑E peptide restores cell size, shape, adhesion, and movement without changing the upstream RhoA protein level.
- The restorative effects depend on the MEK‑ERK1/2 pathway for morphology and the PI3K‑Akt pathway for cell area and mobility.
- MGF‑E does not improve the hypoxia‑induced rise in VEGF‑α, but may compensate by boosting cell proliferation.
Practical Outcomes
- For biohackers interested in bone or tissue repair, MGF‑E peptide appears to help stem cells survive and move under low‑oxygen conditions, suggesting a possible role in supporting bone healing. Because the data are limited to cell culture, any real‑world protocol would need to start with very low, cautious dosing and monitor for side effects. Until animal or human studies are available, the peptide should be considered experimental rather than a proven supplement.
Summary
The study shows that a short piece of the IGF‑1 protein called MGF‑E can reverse the harmful effects of very low oxygen on bone‑marrow stem cells in a dish, helping them keep their shape, stick to surfaces, and move around. It works through two well‑known cell‑signalling pathways (ERK1/2 and Akt). However, the work is done in cell culture, not in people, and no dosing or safety information is provided.
Abstract
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<sub>2</sub> 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<sub>2</sub> ) 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.
Study Information
pubmed
2018
2018-02-13T00:00:00.000Z
10.1002/cbf.3327
6
36