4.7 Article

Early-senescent bone marrow mesenchymal stem cells promote C2C12 cell myogenic differentiation by preventing the nuclear translocation of FOXO3

Journal

LIFE SCIENCES
Volume 277, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119520

Keywords

Senescence; Bone mesenchymal stem cells; Myogenic differentiation; FOXO3

Funding

  1. Shanghai Key disciplines program of Health and Family Planning [2017ZZ02010]
  2. National Key Research and Development Program of Strategic Advanced Electronic Materials [2017YFB0403803]

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This study demonstrated that early-senescent BMSCs accelerate the myogenic differentiation of C2C12 cells, with the transcription factor FOXO3 being the target of the senescent cells. The AKT/P70 signaling pathway mediates the effect of BMSCs on neighboring cells, as seen through the promotion of muscle differentiation by BMSC-derived exosomes.
Aims: Mouse bone marrow mesenchymal stem cells (BMSCs) are pluripotent cells with self-renewal and differentiation abilities. Since the effects of senescent BMSCs on C2C12 cells are not fully clear, the present study aimed to elucidate these effects. Main methods: Senescence-associated beta-galactosidase staining and western blotting were performed to confirm the senescence of BMSCs. Immunofluorescence and western blotting were used to assess myoblast differentiation in each group. The role of the AKT/P70 signaling pathway and forkhead box O3 (FOXO3) nuclear translocation was explored by western blotting. BMSC-derived exosomes were injected into the tibialis anterior of mice, and RT-qPCR was used to assess the role of exosomes in promoting muscle differentiation. Key findings: Conditioned medium (CM) from early-senescent BMSCs promoted myogenic differentiation in vitro, which was detected as enhanced expression of myosin heavy chain (MHC), myogenin (MYOG), and myogenic differentiation 1 (MyoD). The AKT signaling pathway was found to be regulated by CM, which inhibited FOXO3 nuclear translocation. RT-qPCR analysis results showed that MHC, MyoD, and MYOG mRNA expression increased in the tibialis anterior of mice after exosome injection. Significance: The present study demonstrated that early-senescent BMSCs accelerated C2C12 cell myogenic differentiation, and the transcription factor, FOXO3, was the target of senescent cells. Collectively, our results suggest that the AKT/P70 signaling pathway mediates the effect of BMSCs on neighboring cells.

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