Aims: This study aimed to investigate the effects of resveratrol (3, 4', 5-trihydroxystilbene, RES) on osteoporosis and the role of SIRT1/FoxO1 pathway in the process.
Main methods: In vivo, mice were divided into 3 groups, Sham, ovariectomized (OVX) and OVX-RES group. Micro-CT, histology and histomorphometry were conducted to detect details of bone mass and microstructure. The expression of osteoblast markers was tested by Real-time qPCR and serum markers which reflected bone formation and resorption were analyzed by enzyme-linked immunosorbent assay (ELISA). Besides, we assayed sirtuin 1 (SIRT1) expression and the concentration of serum superoxide dismutase (SOD). In vitro, osteoblasts were seperated into 3 groups: control, H2O2 (hydrogen peroxide, H2O2) and H2O2-RES group. Cell proliferation, differentiation and apoptosis were detected. In addition, we tested intracellular reactive oxygen species (ROS) formation and SOD activity detection of osteoblasts. The SIRT1, acetylated FoxO1 (Ac-FoxO1) and nuclear FoxO1 (Nu-FoxO1) expression were detected by western blot.
Key findings: Results revealed that RES could ameliorate bone loss and promote osteogenesis by reinforcing resistance of oxidative stress in OVX mice. RES enhanced proliferation, differentiation and suppressed apoptosis of H2O2-treated osteoblasts. In this process, SIRT1 was upregulated and the level of Nu-FoxO1, which had high transcriptional activity to regulate redox balance, significantly increased.
Significance: Oxidative stress plays a crucial role in osteoporosis. RES can reinforce resistance to oxidative damage and hence promote osteogenesis via the activation of SIRT1/FoxO1 signaling pathway, which provides a new idea for the prevention and treatment of osteoporosis.
Keywords: Forkhead transcription factor 1; Osteogenesis; Osteoporosis; Oxidative stress; Resveratrol; Sirtuin 1.
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