Differential Responses of Myogenic C2C12 Cells to Hypoxia between Growth and Muscle-Induction Phases: Growth, Differentiation and Motility

Abstract

[Introduction] Local hypoxia plays a favorable role in muscle regeneration. [Subjects and Methods] The effect of hypoxia on cell growth, differentiation, and motility was examined in differentiating and growing C2C12 mouse myoblasts cells, respectively. [Results] Hypoxia induced growth suppression in the growth phase, but the suppression diminished in the differentiation phase. Hypoxia inhibited the expression of differentiation marker proteins, accompanying MyoD mRNA suppression. Expression of HIF-1α protein was induced only in the induction phase, regardless of oxygen concentration. Hypoxia did not alter motile activity in the growing phase, but augmented the motile property in the differentiation phase. Expression of autocrine motility factor mRNA was augmented under hypoxic conditions. [Conclusion] In differentiating cells, HIF-1α induced by myogenic differentiation may compensate for the cell growth suppression due to hypoxia, and support the motility augmentation. Hypoxia may shift differentiating cells into the growth phase which provides the ability to translocate to an appropriate area.