Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells

Abstract

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.

Ginsenoside Rg3 Alleviates Aluminum Chloride-Induced Bone Impairment in Rats by Activating the TGF-β1/Smad Signaling Pathway

“…TβRI and TβRII combine with TGF-β1 to form a TβRII-TGF-β1-TβRI heterotetramer complex. Smad2 and Smad3 can be activated by the complex and form a complex with Smad4, transferring the signal into the nucleus and so regulating the downstream gene expression. , Some studies have shown that Rg3 exhibits different biological activities and improves the human mesenchymal stem cell proliferation and differentiation . In addition, Rg3 promotes human endothelial cell proliferation via PI3K/Akt and MAPK/ERK pathways .…”

Klotho prevents transforming growth factor-β2-induced senescent-like morphological changes in the retinal pigment epithelium

“…After culturing, the cells were changed to pre-warmed XF DMEM medium (for OCR measurement, containing 1 M glucose, 100 mM pyruvate and 200 mM L-glutamate and adjusted at pH 7.4; Agilent Technologies) 1 h prior to analyses and kept cells at 37 °C without CO 2 . OCR was measured in human bone marrow stem cells (hBMSCs) using the Seahorse XFe96 Analyzer (Agilent Technologies) to determine the oxygen consumption in response to the addition of various chemicals [ 40 ]. The cycles (3 times for 3 min) were run for every measurement and the Mitostress kit (Agilent Technologies), containing the following compounds: 2 μM oligomycin (ATP synthase inhibitor), 2 μM carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP) (mitochondrial uncoupler), 0.5 μM rotenone (respiratory chain complex I inhibitor), and antimycin A (complex III inhibitor), was used.…”

Ginsenosides on stem cells fate specification—a novel perspective

“…Ginsenoside Rg2 activates AMPK-mediated autophagy restores pig MSCs proliferation and inhibits oxidative stress-induced replicative senescence in pig MSCs ( Che et al, 2023 ). Ginsenoside Rg3 mainly enhances the biogenesis ability of mitochondria and antioxidant function by promoting Ca 2+ concentration properly, thus improving proliferation and differentiation potential and preventing human MSCs from aging ( Hong et al, 2020 ). These results suggest that administration of ginsenosides may be a promising approach to counteract MSC aging by intervening in oxidative stress-related pathways ( Figure 1 ).…”