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

• DOI: 10.1016/j.lfs.2021.119520
• Publication Date: 2021-04-19T22:48:31Z
• Authors: Ji Che; Cuidi Xu; Yuanyuan Wu; Peiyu Jia; Qi Han; Yantao Ma; Xiaolei Wang; Yijie Du; Yongjun Zheng
• Keywords: Cell Nucleus; 0301 basic medicine; TOR Serine-Threonine Kinases; Forkhead Box Protein O3; Active Transport, Cell Nucleus; Bone Marrow Cells; Cell Differentiation; Mesenchymal Stem Cells; Muscle Development; Cell Line; Myoblasts; Mice; 03 medical and health sciences; Animals; Myogenin; Muscle, Skeletal; Proto-Oncogene Proteins c-akt; Cellular Senescence; Cell Proliferation; Signal Transduction

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.Senescence-associated β-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.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.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.