Attenuation of Oxidative Stress-Induced Osteoblast Apoptosis by Curcumin is Associated with Preservation of Mitochondrial Functions and Increased Akt-GSK3β Signaling

Abstract

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 stressinduced osteoblast apoptosis remain unclear. This study aimed to explore the effect of curcumin on hydrogen peroxide (H 2 O 2 ) induced osteoblast apoptosis and the underlying mechanisms. Methods: An osteoblastic cell line (Saos-2) was exposed to various concentrations of H 2 O 2 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 H 2 O 2 and attenuated H 2 O 2 -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-3β (GSK3β). Conclusion: Curcumin administration ameliorates oxidative stress-induced apoptosis in osteoblasts by preserving mitochondrial functions and activation of Akt-GSK3β signaling. These data provide experimental evidence supporting the clinical use of curcumin for prevention or treatment of osteoporosis.P. Dai and Y. Mao contributed equally to this work.

Antioxidant Effect of Fructus Ligustri Lucidi Aqueous Extract in Ovariectomized Rats Is Mediated through Nox4-ROS-NF-κB Pathway

“…It has been revealed that antioxidant-based dietary approach is beneficial to osteoporosis prevention and treatment in Brazilian women (De Franca et al, 2013). In addition, attenuation of H 2 O 2 stimulation increases osteoblasts viabilities and differentiation (Yan et al, 2017) through improving the mitochondrial redox homeostasis and functions (Dai et al, 2017). Elimination of ROS generation inhibits bone resorption through receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) mediated NF-κB activation (Thummuri et al, 2015).…”

The Key Roles of GSK-3β in Regulating Mitochondrial Activity

“…Curcumin, a natural versatile compound from Curcuma longa , has been shown to improve the mitochondrial functions, decrease mitochondrial oxidative stress, and prevent cell apoptosis through activation of Akt/GSK-3β signaling in Saos-2 cells [80]. Resveratrol, the most famous polyphenol, significantly alleviates MPP+-induced mitochondrial dysfunctions through activation of Akt-GSK-3β signaling in SN4741 cells [81].…”

Exercise Training Attenuates Proinflammatory Cytokines, Oxidative Stress and Modulates Neurotransmitters in the Rostral Ventrolateral Medulla of Salt-Induced Hypertensive Rats

“…Measurement of RVLM protein was performed as previously described [28,30]. Briefly, protein extracted from the RVLM was used for measurements of TNF-α, the 67-kDa isoform of glutamate decarboxylase (GAD67), atrial natriuretic peptide (ANP), beta-myosin heavy chain (β-MHC), NAD(P)H oxidase subunit NOX 2 (gp91 phox ) and NOX 4 (Santa Cruz Biotechnology Inc, Santa Cruz, California) expressions by western blot.…”