Although mitochondrial functions are essential for cell survival, their critical roles in stem cell fate, including proliferation, differentiation, and senescence, remain elusive. Ginsenoside Rg3 exhibits various biological activities and reportedly increases mitochondrial biogenesis and respiration. Herein, we observed that Rg3 increased proliferation and suppressed senescence of human bone marrow-derived mesenchymal stem cells. Osteogenic, but not adipogenic, differentiation was facilitated by Rg3 treatment. Rg3 suppressed reactive oxygen species production and upregulated mitochondrial biogenesis and antioxidant enzymes, including superoxide dismutase. Consistently, Rg3 strongly augmented basal and ATP synthesis-linked respiration with high spare respiratory capacity. Rg3 treatment elevated cytosolic Ca2+ concentration contributing to mitochondrial activation. Reduction of intracellular or extracellular Ca2+ levels strongly inhibited Rg3-induced activation of mitochondrial respiration and biogenesis. Taken together, Rg3 enhances capabilities of mitochondrial and antioxidant functions mainly through a Ca2+-dependent pathway, which improves the proliferation and differentiation potentials and prevents the senescence of human mesenchymal stem cells.
Bibliographical noteFunding Information:
The research grants of Medical Research Center Program (2017R1A5A2015369) and Bio & Medical Technology Development Program (NRF-2020M3A9D8039920) from the Ministry of Science, ICT, Republic of Korea and the Yonsei University Wonju Campus Future-Leading Research Initiative of 2018 (2018-62-0055) were used in performing experiments, data analysis, and writing the manuscript. Acknowledgements
This work was supported by the Medical Research Center Program (2017R1A5A2015369) and Bio & Medical Technology Development Program (NRF-2020M3A9D8039920) from the Ministry of Science, ICT, and the Yonsei University Wonju Campus Future-Leading Research Initiative of 2018 (2018-62-0055).
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Molecular Medicine
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Cell Biology