Objective: 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.

Methods: Cell senescence, viability, and osteogenic differentiation of BMSCs influenced by resveratrol were investigated and ROS production and AMPK expression were detected.

Results: 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.

Conclusion: 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.

目的：白藜芦醇已被证实具有改善骨质量、延缓骨质疏松的作用，但其机制尚未彻底阐明。在本报告中，我们研究了白藜芦醇对衰老骨间充质干细胞（BMSC）的成骨分化作用以及AMP激活蛋白激酶（AMPK）/活性氧（ROS）信号通路的参与。

方法：研究白藜芦醇对BMSCs细胞衰老、活力和成骨分化的影响，并检测ROS产生和AMPK表达。

结果：白藜芦醇可减弱细胞衰老，其特征是衰老 β-半乳糖苷酶染色和衰老相关基因（p16、p21 和 p53）表达。白藜芦醇治疗后，细胞活力、细胞外基质钙化和成骨相关基因表达显着增强。白藜芦醇抑制 BMSC 中 ROS 的产生，同时上调 AMPK 的表达。化合物 C 抑制 AMPK 表达可减少白藜芦醇促进的成骨和 ROS 产生下调。

结论：这些结果提供了白藜芦醇增强BMSCs成骨分化中涉及AMPK激活/ROS抑制信号通路的潜在机制。这表明针对ROS的治疗的发展是治疗骨质疏松症的有效途径。