Dexamethasone induces osteoblast apoptosis through ROS-PI3K/AKT/GSK3β signaling pathway - 06/01/19
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Graphical abstract |
Highlights |
• | Dex inhibits proliferation and induces apoptosis of osteoblasts. |
• | Dex enhances the ROS levels in osteoblasts. |
• | Dex suppresses the activation of PI3K/AKT signaling pathway in osteoblasts. |
• | Dex promotes the activation of GSK-3β in osteoblasts. |
• | Knockdown of GSK3β reverses the Dex-induced osteoblast apoptosis. |
Abstract |
Background |
Osteoblasts play important roles in the process of osteogenesis and prevention of osteonecrosis. Dexamethasone (Dex), a type of glucocorticoids (GCs), induces apoptosis of osteoblasts and leads to the occurrence of non-traumatic osteonecrosis. This study aimed to explore the effects of phosphatidylinositol 3-kinase/Protein kinase 3 (PI3K/AKT) and glycogen synthase kinase 3β (GSK3β) on Dex-induced osteoblasts apoptosis.
Methods |
Viabilities, proliferation, and apoptosis of primary osteoblasts and pre-osteoblast MC3T3-E1 cells after Dex treatment were detected using cell counting kit-8 (CCK-8) assay, 5-bromo-2′-deoxyuridine (BrdU) incorporation assay, FITC-Annexin V/PI staining and western blotting, respectively. 2′,7′-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining was performed to measure the intracellular reactive oxygen species (ROS) levels after Dex treatment. N-acetyl-l-cysteine (NAC) was used as ROS scavenger in this research. The expressions of PI3K/AKT and GSK3β in osteoblasts and MC3T3-E1 cells after Dex treatment were analyzed using western blotting and qRT-PCR, respectively. Then the effects of GSK3β knockdown on Dex-induced apoptosis of osteoblasts were explored. Alkaline phosphatase (ALP) activity assay was used to detect the role of Dex in regulating ALP activity.
Results |
Dex remarkably inhibited proliferation and induced apoptosis of osteoblasts and MC3T3-E1 cells. Dex potentially attenuated the osteoblast differentiation. The intracellular ROS levels were significantly increased after Dex treatment. Dex suppressed the activation of PI3K/AKT pathway in osteoblasts and MC3T3-E1 cells by down-regulating the expressions of p-PI3K and p-AKT. The expressions of GSK3β in osteoblasts and MC3T3-E1 cells were obviously up-regulated after Dex treatment. Knockdown of GSK3β alleviated Dex-induced osteoblast and MC3T3-E1 cell apoptosis by decreasing the expressions of Bax, cleaved-caspase 3, cleaved-caspase 9 and increasing the expression of Bcl-2.
Conclusion |
Our research verified that Dex induced osteoblasts apoptosis by ROS-PI3K/AKT/GSK3β signaling pathway.
Le texte complet de cet article est disponible en PDF.Keywords : Osteonecrosis, Osteoblasts apoptosis, Dexamethasone, Reactive oxygen species, Phosphatidylinositol 3-kinase/protein kinase 3, Glycogen synthase kinase 3β
Plan
Vol 110
P. 602-608 - février 2019 Retour au numéro
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