Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells
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.
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Posted 22 Sep, 2020
On 04 Nov, 2020
On 01 Oct, 2020
On 28 Sep, 2020
Received 28 Sep, 2020
Invitations sent on 25 Sep, 2020
On 25 Sep, 2020
Received 25 Sep, 2020
On 21 Sep, 2020
On 20 Sep, 2020
On 20 Sep, 2020
On 04 Sep, 2020
Received 03 Sep, 2020
On 24 Aug, 2020
Received 24 Aug, 2020
On 22 Aug, 2020
Invitations sent on 20 Aug, 2020
On 14 Aug, 2020
On 13 Aug, 2020
On 13 Aug, 2020
On 12 Aug, 2020
Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells
Posted 22 Sep, 2020
On 04 Nov, 2020
On 01 Oct, 2020
On 28 Sep, 2020
Received 28 Sep, 2020
Invitations sent on 25 Sep, 2020
On 25 Sep, 2020
Received 25 Sep, 2020
On 21 Sep, 2020
On 20 Sep, 2020
On 20 Sep, 2020
On 04 Sep, 2020
Received 03 Sep, 2020
On 24 Aug, 2020
Received 24 Aug, 2020
On 22 Aug, 2020
Invitations sent on 20 Aug, 2020
On 14 Aug, 2020
On 13 Aug, 2020
On 13 Aug, 2020
On 12 Aug, 2020
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.
Figure 1
Figure 2
Figure 3