Abstract
Studies showed that energy metabolism plays a pivotal role in the differentiation of stem cells. Previous studies revealed that simulated microgravity (SMG) inhibits osteogenic differentiation of mesenchymal stem cells (MSCs). However, the underlying relationship between osteogenesis and energy metabolism under SMG conditions is not fully understood. In the present study, we investigated mitochondrial oxidative phosphorylation (OXPHOS) by assessing the level of peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α), mitochondrial DNA (mtDNA) copy number, mitochondrial mass and oxygen consumption rate (OCR) during osteogenesis of MSCs under SMG conditions. We found that SMG inhibited osteogenic differentiation and OXPHOS of MSCs. Moreover, the expression of sirtuin 1 (Sirt1), an important energy sensor, significantly decreased. After upregulating the expression of Sirt1 using resveratrol, an activator of Sirt1, SMG-inhibited OXPHOS and osteogenic differentiation of MSCs were recovered. Taken together, our results suggest that SMG suppresses osteogenic differentiation of MSCs by inhibiting OXPHOS, indicating that OXPHOS might serve as a potential therapeutic target for repairing bone loss under microgravity conditions.
Highlights
One of the health problems that astronauts face after a long spaceflight is bone loss
The data in these study indicate that activating oxidative phosphorylation (OXPHOS) via sirtuin 1 (Sirt1) could reverse the inhibition of simulated gravity (SMG) on osteogenic differentiation of Mesenchymal stem cells (MSCs)
It was reported that MSCs prefer glycolysis for energy supply [17], but when MSCs commit to differentiation, much more energy is required for differentiation, which is consistent with the activation of OXPHOS [18]
Summary
One of the health problems that astronauts face after a long spaceflight is bone loss. A growing body of evidence indicates that osteogenic differentiation of MSCs is inhibited by weightlessness [2], which means that gravity is necessary and crucial for the regulation of bone remodeling and homeostasis [3]. Studies confirmed that OXPHOS is important and necessary for osteogenic differentiation of MSCs in vitro [6,7], which indicates that OXPHOS plays a crucial role in the process of osteogenesis. We explored the role of energy metabolism in osteogenic differentiation of MSCs under SMG conditions, by investigating the changes in OXPHOS and Sirt levels in this study. Our data indicate that the inhibition of osteogenesis of MSCs induced by SMG is due to decreased Sirt expression, followed by the repression of OXPHOS
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