Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

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*

Volume 22, Issue 4, 2022

Published on: 09 August, 2021

Page: [354 - 364] Pages: 11

DOI: 10.2174/1566524021666210614144337

Price: $65

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.

« Previous Next »
[1]
Schwartz AV. Efficacy of Osteoporosis Therapies in Diabetic Patients. Calcif Tissue Int 2017; 100(2): 165-73.
[http://dx.doi.org/10.1007/s00223-016-0177-8] [PMID: 27461216]
[2]
Kurra S, Fink DA, Siris ES. Osteoporosis-associated fracture and diabetes. Endocrinol Metab Clin North Am 2014; 43(1): 233-43.
[http://dx.doi.org/10.1016/j.ecl.2013.09.004] [PMID: 24582100]
[3]
Hofbauer LC, Brueck CC, Singh SK, Dobnig H. Osteoporosis in patients with diabetes mellitus.Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 2007; 22(9): 1317-28.
[http://dx.doi.org/10.1359/jbmr.070510]
[4]
Coughlan T, Dockery F. Osteoporosis and fracture risk in older people. Clin Med (Lond) 2014; 14(2): 187-91.
[http://dx.doi.org/10.7861/clinmedicine.14-2-187] [PMID: 24715132]
[5]
Caetano-Lopes J, Canhão H, Fonseca JE. Osteoblasts and bone formation. Acta Reumatol Port 2007; 32(2): 103-10.
[PMID: 17572649]
[6]
Wang X, Feng Z, Li J, Chen L, Tang W. High glucose induces autophagy of MC3T3-E1 cells via ROS-AKT-mTOR axis. Mol Cell Endocrinol 2016; 429: 62-72.
[http://dx.doi.org/10.1016/j.mce.2016.03.036] [PMID: 27068641]
[7]
Dong K, Hao P, Xu S, Liu S, Zhou W, Yue X, et al. Alpha- Lipoic Acid Alleviates High-Glucose Suppressed Osteogenic Differentiation of MC3T3-E1 Cells via Antioxidant Effect and PI3K/Akt Signaling Pathway. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology 2017; 42(5): 1897-906.a
[8]
Andreyev AY, Kushnareva YE, Starkov AA. Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc) 2005; 70(2): 200-14.
[http://dx.doi.org/10.1007/s10541-005-0102-7] [PMID: 15807660]
[9]
Dong C, Wu G, Li H, Qiao Y, Gao S. Ampelopsin inhibits high glucose-induced extracellular matrix accumulation and oxidative stress in mesangial cells through activating the Nrf2/HO-1 pathway. Phytother Res 2020; 34(8): 2044-52.
[http://dx.doi.org/10.1002/ptr.6668] [PMID: 32155298]
[10]
Kogame M, Matsuo S, Nakatani M, et al. ALK7 is a novel marker for adipocyte differentiation. J Med Invest 2006; 53(3-4): 238-45.
[http://dx.doi.org/10.2152/jmi.53.238] [PMID: 16953060]
[11]
Murakami M, Shirai M, Ooishi R, et al. Expression of activin receptor-like kinase 7 in adipose tissues. Biochem Genet 2013; 51(3-4): 202-10.
[http://dx.doi.org/10.1007/s10528-012-9555-8] [PMID: 23264230]
[12]
Bertolino P, Holmberg R, Reissmann E, Andersson O, Berggren PO, Ibáñez CF. Activin B receptor ALK7 is a negative regulator of pancreatic beta-cell function. Proc Natl Acad Sci USA 2008; 105(20): 7246-51.
[http://dx.doi.org/10.1073/pnas.0801285105] [PMID: 18480258]
[13]
Jörnvall H, Reissmann E, Andersson O, Mehrkash M, Ibáñez CF. ALK7, a receptor for nodal, is dispensable for embryogenesis and left-right patterning in the mouse. Mol Cell Biol 2004; 24(21): 9383-9.
[http://dx.doi.org/10.1128/MCB.24.21.9383-9389.2004] [PMID: 15485907]
[14]
Bu Y, Okunishi K, Yogosawa S, et al. Insulin regulates lipolysis and fat mass by upregulating growth/differentiation factor 3 in adipose tissue macrophages. Diabetes 2018; 67(9): 1761-72.
[http://dx.doi.org/10.2337/db17-1201] [PMID: 29945891]
[15]
Yogosawa S, Mizutani S, Ogawa Y, Izumi T. Activin receptor-like kinase 7 suppresses lipolysis to accumulate fat in obesity through downregulation of peroxisome proliferator-activated receptor γ and C/EBPα. Diabetes 2013; 62(1): 115-23.
[http://dx.doi.org/10.2337/db12-0295] [PMID: 22933117]
[16]
Liu L, Ding WY, Zhao J, et al. Activin receptor-like kinase 7 mediates high glucose-induced H9c2 cardiomyoblast apoptosis through activation of Smad2/3. Int J Biochem Cell Biol 2013; 45(9): 2027-35.
[http://dx.doi.org/10.1016/j.biocel.2013.06.018] [PMID: 23830891]
[17]
Michael IP, Saghafinia S, Tichet M, et al. ALK7 Signaling Manifests a Homeostatic Tissue Barrier That Is Abrogated during Tumorigenesis and Metastasis. Dev Cell 2019; 49(3): 409-424.e6.
[http://dx.doi.org/10.1016/j.devcel.2019.04.015] [PMID: 31063757]
[18]
Li WB, Zhao J, Liu L, et al. Silencing of activin receptor-like kinase 7 alleviates aortic stiffness in type 2 diabetic rats. Acta Diabetol 2015; 52(4): 717-26.
[http://dx.doi.org/10.1007/s00592-014-0706-8] [PMID: 25577243]
[19]
Shi Q, Dong X, Zhang M, Cheng Y, Pei C. Knockdown of ALK7 inhibits high glucose-induced oxidative stress and apoptosis in retinal pigment epithelial cells. Clin Exp Pharmacol Physiol 2020; 47(2): 313-21.
[http://dx.doi.org/10.1111/1440-1681.13189] [PMID: 31608496]
[20]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Method Methods 2001; 25(4): 402-8.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[21]
Du X, Li Q, Cao Q, Wang S, Liu H, Li Q. Integrated Analysis of miRNA-mRNA Interaction Network in Porcine Granulosa Cells Undergoing Oxidative Stress. Oxid Med Cell Longev 2019; 2019: 1041583.
[http://dx.doi.org/10.1155/2019/1041583] [PMID: 31781320]
[22]
Fan YS, Li Q, Hamdan N, et al. Tetrahydroxystilbene Glucoside Regulates Proliferation, Differentiation, and OPG/RANKL/M-CSF Expression in MC3T3-E1 Cells via the PI3K/Akt Pathway. Molecules 2018; 23(9): E2306.
[http://dx.doi.org/10.3390/molecules23092306] [PMID: 30201908]
[23]
Liu B, Li J, Cairns MJ. Identifying miRNAs, targets and functions. Brief Bioinform 2014; 15(1): 1-19.
[http://dx.doi.org/10.1093/bib/bbs075] [PMID: 23175680]
[24]
Jiang F, Shan H, Pan C, et al. ATP6V1H facilitates osteogenic differentiation in MC3T3-E1 cells via Akt/GSK3β signaling pathway. Organogenesis 2019; 15(2): 43-54.
[http://dx.doi.org/10.1080/15476278.2019.1633869] [PMID: 31272281]
[25]
Tan J, Zhou L, Zhou Y, et al. The Influence of Diabetes Mellitus on Proliferation and Osteoblastic Differentiation of MSCs. Curr Stem Cell Res Ther 2017; 12(5): 388-400.
[http://dx.doi.org/10.2174/1574888X10666151001114527] [PMID: 26423300]
[26]
Silva JC, Sampaio P, Fernandes MH, Gomes PS. The osteogenic priming of mesenchymal stem cells is impaired in experimental diabetes. J Cell Biochem 2015; 116(8): 1658-67.
[http://dx.doi.org/10.1002/jcb.25126] [PMID: 25704854]
[27]
Wang Y, Chen H, Zhang H. Kaempferol promotes proliferation, migration and differentiation of MC3T3-E1 cells via up-regulation of microRNA-101. Artif Cells Nanomed Biotechnol 2019; 47(1): 1050-6.
[http://dx.doi.org/10.1080/21691401.2019.1591428] [PMID: 30942633]
[28]
Li G, Jiang X, Liu L, Liu X, Liu H, Zhang Z. Effect of estradiol on high glucose induced osteoblast injury. Mol Med Rep 2019; 20(4): 3019-26.
[http://dx.doi.org/10.3892/mmr.2019.10552] [PMID: 31432111]
[29]
Salazar VS, Gamer LW, Rosen V. BMP signalling in skeletal development, disease and repair. Nat Rev Endocrinol 2016; 12(4): 203-21.
[http://dx.doi.org/10.1038/nrendo.2016.12] [PMID: 26893264]
[30]
Doustimotlagh AH, Dehpour AR, Etemad-Moghadam S, Alaeddini M, Ostadhadi S, Golestani A. A study on OPG/RANK/RANKL axis in osteoporotic bile duct-ligated rats and the involvement of nitrergic and opioidergic systems. Res Pharm Sci 2018; 13(3): 239-49.
[http://dx.doi.org/10.4103/1735-5362.228954] [PMID: 29853933]
[31]
Yu X, Liu W, Fan Z, et al. c-Myb knockdown increases the neomycin-induced damage to hair-cell-like HEI-OC1 cells in vitro. Sci Rep 2017; 7: 41094.
[http://dx.doi.org/10.1038/srep41094] [PMID: 28112219]
[32]
Martins CM, de Azevedo Queiroz IO, Ervolino E, Cintra LTA, Gomes-Filho JE. RUNX-2, OPN and OCN expression induced by grey and white mineral trioxide aggregate in normal and hypertensive rats. Int Endod J 2018; 51(6): 641-8.
[http://dx.doi.org/10.1111/iej.12876] [PMID: 29143348]
[33]
Ashrafizadeh M, Ahmadi Z, Mohammadinejad R, Farkhondeh T, Samarghandian S. Curcumin Activates the Nrf2 Pathway and Induces Cellular Protection Against Oxidative Injury. Curr Mol Med 2020; 20(2): 116-33.
[http://dx.doi.org/10.2174/1566524019666191016150757] [PMID: 31622191]
[34]
Xing Y, Ji Q, Li X, Ming J, Zhang N, Zha D, et al. Asiaticoside protects cochlear hair cells from high glucose-induced oxidative stress via suppressing AGEs/RAGE/NF-κB pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2017; 86: 531-6.
[35]
Jia Q, Wang Y, Liu X, Ma S, Yang R. [Effects of genistein on Nrf2/HO-1 pathway in myocardial tissues of diabetic rats]. Zhong nan da xue xue bao Yi xue ban = Journal of Central South University Medical sciences 2019; 44(8): 850-6.
[36]
Sun W, Yu J, Kang Q. Upregulation of heme oxygenase-1 by Brahma-related gene 1 through Nrf2 signaling confers protective effect against high glucose-induced oxidative damage of retinal ganglion cells. Eur J Pharmacol 2020; 875: 173038.
[http://dx.doi.org/10.1016/j.ejphar.2020.173038] [PMID: 32105681]
[37]
Principe M, Chanal M, Karam V, et al. ALK7 expression in prolactinoma is associated with reduced prolactin and increased proliferation. Endocr Relat Cancer 2018; 25(9): 795-806.
[http://dx.doi.org/10.1530/ERC-18-0082] [PMID: 30012586]
[38]
Wang X, Martindale JL, Liu Y, Holbrook NJ. The cellular response to oxidative stress: influences of mitogen-activated protein kinase signalling pathways on cell survival. The Biochemical journal 1998; 333(2): 291-300.
[http://dx.doi.org/10.1042/bj3330291]
[39]
Nguyen DT, Lee E, Alimperti S, et al. A biomimetic pancreatic cancer on-chip reveals endothelial ablation via ALK7 signaling. Sci Adv 2019; 5(8): eaav6789.
[http://dx.doi.org/10.1126/sciadv.aav6789] [PMID: 31489365]

Rights & Permissions Print Cite
Article Metrics
50
1
World Malaria Day
© 2024 Bentham Science Publishers | Privacy Policy