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ALK7 Inhibition Protects Osteoblast Cells Against High Glucoseinduced ROS Production via Nrf2/HO-1 Signaling Pathway

Author(s):

Zhen Zhao, Yu Lu, Huan Wang, Xiang Gu, Luting Zhu, Hong Guo and Nan Li*   Pages 1 - 11 ( 11 )

Abstract:


Background: Some studies demonstrated that under high-glucose (HG) condition, osteoblasts develop oxidative stress, which will impair their normal functions. The effects of activin receptor-like kinase 7 (ALK7) silencing on HG-induced osteoblasts remained unclear.

Objective: The aim of this study was to explore the effect of ALK7 on HG-induced osteoblasts.

Methods: MC3T3-E1 cells were treated with different concentrations of HG (0, 50, 100, 200 and 300mg/dL), and the cell viability was detected using cell counting kit-8 (CCK-8). HG-treated MC3T3-E1 cells were transfected with siALK7 or ALK7 overexpression plasmid or siNrf2, and then the viability and apoptosis were detected by CCK-8 and flow cytometry. The levels of Reactive Oxygen Species (ROS), collagen I and calcification nodule were determined by oxidative stress kits, Enzyme-linked immunosorbent assay and Alizarin red staining. The expressions of NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and osteoblast-associated genes were determined by quantitative real-time PCR (qRT-PCR) and Western blot.

Results: Cell viability was reduced with HG treatment. Silencing ALK7 inhibited the effect of HG on increasing cell apoptosis and ROS production, reduced cell viability, mineralized nodules, and downregulated collagen I and osteoblast-associated genes expression in MC3T3-E1 cells. ALK7 silencing activated the Nrf2/HO-1 signaling pathway by affecting expressions of HO-1 and Nrf2. ALK7 overexpression had the opposite effects. In addition, siNrf2 partially reversed the effects of ALK7 silencing on HG-induced MC3T3-E1 cells.

Conclusion: ALK7 silencing protected osteoblasts under HG condition possibly through activating the Nrf2/HO-1 pathway.

Keywords:

ALK7, osteoblasts, high glucose, reactive oxygen species, Nrf2/HO-1 signaling pathway, diabetic osteoporosis.

Affiliation:

Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Xicheng District, Beijing, 100050, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Xicheng District, Beijing, 100050, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Xicheng District, Beijing, 100050, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Xicheng District, Beijing, 100050, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Xicheng District, Beijing, 100050, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Xicheng District, Beijing, 100050, Department of Endocrinology, The Second Medical Center & National Clinical Research Center, Chinese PLA General Hospital, Haidian District, Beijing, 100853



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