MGF E peptide pretreatment improves the proliferation and osteogenic differentiation of BMSCs via MEK-ERK1/2 and PI3K-Akt pathway under severe hypoxia.
Sha. Yongqiang Y; Lv. Yonggang Y; Xu. Zhiling Z; Yang. Li L; Hao. Xiaoying X; Afandi. Ruli R
Key Findings
- MGF‑E peptide reduces HIF‑1α buildup and its movement into the cell nucleus under severe hypoxia
- Cell proliferation and bone‑forming (osteogenic) differentiation of BMSCs are restored after MGF‑E pretreatment
- The beneficial effects involve activation of MEK‑ERK1/2 and PI3K‑Akt signaling pathways
- Even a brief exposure to MGF‑E alone can boost osteogenic differentiation
Practical Outcomes
- For biohackers interested in bone health, MGF‑E could be explored as a supplement to support bone repair, especially when tissue oxygen is low. However, the research is limited to lab cells, so safe dosing, delivery method, and real‑world efficacy remain untested. Any trial should start with very low doses and consider combining with other bone‑supporting practices like proper nutrition, mechanical loading, and possibly animal‑model data before human use.
Summary
The study shows that a short pre‑treatment with the MGF‑E peptide can help bone‑marrow stem cells keep growing and turn into bone‑forming cells even when oxygen levels are very low. It works by lowering a stress protein (HIF‑1α) and activating two cell‑signaling pathways (MEK‑ERK1/2 and PI3K‑Akt). While this is only cell‑culture work, it hints that MGF‑E might aid bone healing in tough conditions like injuries or surgeries where blood flow is limited.
Abstract
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. CoCl<sub>2</sub> 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. 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 14days. 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.
Study Information
pubmed
2017
2017-09-18T00:00:00.000Z
10.1016/j.lfs.2017.09.017
27
44