MGF E peptide pretreatment improves the proliferation and osteogenic differentiation of BMSCsviaMEK-ERK1/2 and PI3K-Akt pathway under severe hypoxia

    loading  Checking for direct PDF access through Ovid



Severe hypoxia always inhibits the cell proliferation, osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), and hinders bone defect repair. Herein we explored the effects of mechano-growth factor (MGF) E peptide on the proliferation and osteogenic differentiation of BMSCs under severe hypoxia.

Materials and methods:

CoCl2 was utilized to simulate severe hypoxia. MTS was used to detect cell viability. Cell proliferation was verified through flow cytometry and EdU assay. Osteogenic differentiation of BMSCs and osteoblast-specific genes were detected through alkaline phosphatase (ALP) and Alizarin Red S staining, and quantitative real-time PCR, respectively. Hypoxia-inducible factor 1α (HIF-1α), p-ERK1/2 and p-Akt expression levels were detected through western blotting and immunofluorescence.

Key findings:

Severe hypoxia induced HIF-1α accumulation and transferring into the nucleus, and reduced cell proliferation and osteogenic differentiation of BMSCs. The expression levels of osteoblast-specific genes were markedly decreased after differentiation culture for 0, 7 or 14 days. Fortunately, MGF E peptide inhibited HIF-1α expression and transferring into the nucleus. Cell proliferation and osteogenic differentiation of BMSCs could be recovered by MGF E peptide pretreatment. MEK-ERK1/2 and PI3K-Akt signaling pathway were confirmed to be involved in MGF E peptide regulating the abovementioned indexes of BMSCs. What's more, short-time treatment with MGF E peptide alone promoted the osteogenic differentiation of BMSCs as well.


Our study provides new evidence for the role of MGF E peptide in regulating proliferation and osteogenic differentiation of BMSCs under severe hypoxia, which may potentially have therapeutic implication for bone defect repair.

Related Topics

    loading  Loading Related Articles