Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells
Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells
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DOI：
10.1096/fasebj.22.1_supplement.1197.3
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发表时间：
2008-03
期刊：
影响因子：
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通讯作者：
Yau-Huei Wei;Chien‐Tsun Chen;Yu-Ru V. Shih;T. K. Kuo;O. Lee
中科院分区：
文献类型：
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作者：
Yau-Huei Wei;Chien‐Tsun Chen;Yu-Ru V. Shih;T. K. Kuo;O. Lee
本研究观察了人骨髓间充质干细胞（hMSCs）分化过程中线粒体生物发生和生物能量功能的变化。成骨诱导后，线粒体DNA的拷贝数、呼吸酶的蛋白亚基、耗氧率和细胞内ATP含量增加，表明有氧代谢上调。另一方面，未分化的hMSC显示出更高水平的糖酵解酶和乳酸产生率，这表明与hMSC分化的成骨细胞相比，hMSC更依赖于糖酵解来提供能量。此外，我们观察到细胞内活性氧（ROS）的急剧减少，这是两种抗氧化酶Mn-SOD和过氧化氢酶上调的结果。最后，我们发现H2 O2和线粒体抑制剂延缓了成骨分化。这些发现表明，在成骨诱导后，hMSCs中的能量产生从糖酵解转变为氧化磷酸化。同时，抗氧化酶同时上调，以防止细胞内ROS的积累。总之，我们的研究结果表明，协调调节线粒体生物合成和抗氧化酶发生协同作用，在hMSCs的成骨分化。
We investigated the changes of mitochondrial biogenesis and bioenergetic function of human mesenchymal stem cells (hMSCs) during differentiation. Upon osteogenic induction, the copy number of mitochondrial DNA, protein subunits of the respiratory enzymes, oxygen consumption rate, and intracellular ATP content were increased, indicating the upregulation of aerobic metabolism. On the other hand, undifferentiated hMSCs showed higher levels of glycolytic enzymes and lactate production rate, suggesting that hMSCs rely more on glycolysis for energy supply compared with hMSC‐differentiated osteoblasts. In addition, we observed a dramatic decrease of intracellular reactive oxygen species (ROS) as a consequence of upregulation of two antioxidant enzymes, Mn‐SOD and catalase. Finally, we found that H2O2 and mitochondrial inhibitors retarded the osteogenic differentiation. These findings suggest an energy production transition from glycolysis to oxidative phosphorylation in hMSCs upon osteogenic induction. Meanwhile, antioxidant enzymes were concurrently upregulated to prevent the accumulation of intracellular ROS. Together, our findings suggest that coordinated regulation of mitochondrial biogenesis and antioxidant enzymes occurs synergistically during osteogenic differentiation of hMSCs.