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.

中文翻译：

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Ca ²⁺激活的线粒体生物发生和功能改善了Rg3处理的人间充质干细胞中的干细胞命运

尽管线粒体功能对于细胞存活至关重要，但它们在干细胞命运中的关键作用（包括增殖，分化和衰老）仍然难以捉摸。人参皂苷Rg3具有多种生物学活性，据报道可增加线粒体的生物发生和呼吸作用。在这里，我们观察到Rg3增加人骨髓来源的间充质干细胞的增殖并抑制衰老。Rg3处理可促进成骨而非成脂分化。Rg3抑制了活性氧的产生，并上调了线粒体的生物发生和抗氧化酶，包括超氧化物歧化酶。一致地，Rg3强烈增强了基础呼吸和ATP合成相关的呼吸，并具有较高的备用呼吸能力。Rg3处理提高了细胞质中Ca2 +的浓度，从而促进了线粒体的活化。细胞内或细胞外Ca2 +水平的降低会强烈抑制Rg3诱导的线粒体呼吸激活和生物发生。总之，Rg3主要通过Ca2 +依赖性途径增强线粒体的功能和抗氧化功能，从而改善了增殖和分化潜能，并防止了人间充质干细胞的衰老。