Institute of Biology and Medicine, College of Life Sciences and Health, Wuhan University of Science and Technology , Wuhan , People's Republic of China.
Redox Rep. 2019 Dec;24(1):62-69. doi: 10.1080/13510002.2019.1658376.
Resveratrol has been confirmed to improve bone quality and delay osteoporosis, but the mechanisms have not been thoroughly elucidated. In this report, we investigated the osteogenic differentiation effect of resveratrol on senescent bone mesenchymal stem cells (BMSCs) and the involvement of AMP-activated protein kinase (AMPK)/ reactive oxygen species (ROS) signaling pathway. Cell senescence, viability, and osteogenic differentiation of BMSCs influenced by resveratrol were investigated and ROS production and AMPK expression were detected. Cell senescence, characterized by senescence β-galactosidase staining and senescence-related genes (p16, p21, and p53) expression, was attenuated by resveratrol. Cell viability, extracellular matrix calcification, and osteogenic-related genes expression were significantly enhanced after resveratrol treatment. ROS production in BMSCs was inhibited while AMPK expression was up-regulated by resveratrol. Inhibition of AMPK expression by compound C reduced resveratrol-prompted osteogenesis and ROS production down-regulation. These results provide a potential mechanism involving AMPK activation/ROS inhibition signaling pathway in osteogenic differentiation of BMSCs enhanced by resveratrol. It suggests that development of therapy towards ROS is an effective way for osteoporosis treatment.
白藜芦醇已被证实可改善骨质量并延缓骨质疏松症,但作用机制尚未完全阐明。在本报告中,我们研究了白藜芦醇对衰老骨髓间充质干细胞(BMSCs)的成骨分化作用及其涉及的 AMP 激活蛋白激酶(AMPK)/活性氧(ROS)信号通路。研究了白藜芦醇对 BMSCs 细胞衰老、活力和成骨分化的影响,并检测了 ROS 产生和 AMPK 表达。白藜芦醇减弱了衰老 BMSCs 的衰老β-半乳糖苷酶染色和衰老相关基因(p16、p21 和 p53)表达的细胞衰老。细胞活力、细胞外基质钙化和成骨相关基因表达在白藜芦醇处理后显著增强。白藜芦醇抑制 BMSCs 中的 ROS 产生并上调 AMPK 表达。用化合物 C 抑制 AMPK 表达可减少白藜芦醇诱导的成骨作用并下调 ROS 产生下调。这些结果提供了一个潜在的机制,涉及 AMPK 激活/ROS 抑制信号通路在白藜芦醇增强的 BMSCs 成骨分化中的作用。这表明针对 ROS 的治疗开发是骨质疏松症治疗的有效方法。