Attenuation of Oxidative Stress-Induced Osteoblast Apoptosis by Curcumin is Associated with Preservation of Mitochondrial Functions and Increased Akt-GSK3 beta Signaling

作者:Dai, Panpan; Mao, Yixin; Sun, Xiaoyu; Li, Xumin; Muhammad, Ibrahim; Gu, Weiyan; Zhang, Dafeng; Zhou, Yu; Ni, Zhenyu; Ma, Jianfeng*; Huang, Shengbin*
来源:Cellular Physiology and Biochemistry, 2017, 41(2): 661-677.
DOI:10.1159/000457945

摘要

Background: Osteoblast apoptosis induced by oxidative stress plays a crucial role in the development and progression of osteoporosis. Curcumin, a natural antioxidant isolated from Curcuma longa, has highly protective effects against osteoporosis. However, the effects of curcumin on oxidative stress-induced osteoblast apoptosis remain unclear. This study aimed to explore the effect of curcumin on hydrogen peroxide (H2O2) induced osteoblast apoptosis and the underlying mechanisms. Methods: An osteoblastic cell line (Saos-2) was exposed to various concentrations of H2O2 with or without curcumin treatment. Cell viability was evaluated by MTT assays. The apoptosis rate was analyzed by flow cytometry and TUNEL assays. Mitochondrial ROS and membrane potential were determined using a fluorescence microscope. Mitochondrial respiratory enzyme activity was measured using a spectrophotometer. Protein levels were detected by western blotting. Results: Curcumin was cytoprotective because it greatly improved the viability of Saos-2 cells exposed to H2O2 and attenuated H2O2-induced apoptosis. Curcumin treatment also preserved the mitochondrial redox potential, decreased the mitochondrial oxidative status, and improved the mitochondrial membrane potential and functions. Furthermore, curcumin treatment markedly increased levels of phosphorylated protein kinase B (Akt) and phosphorylated glycogen synthase kinase-3 beta (GSK3 beta). Conclusion: Curcumin administration ameliorates oxidative stress-induced apoptosis in osteoblasts by preserving mitochondrial functions and activation of Akt-GSK3 beta signaling. These data provide experimental evidence supporting the clinical use of curcumin for prevention or treatment of osteoporosis.