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Ameliorating Effect of Osteopontin on H2O2-Induced Apoptosis of Human Oligodendrocyte Progenitor Cells

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Abstract

Recently our group used oligodendrocyte progenitor cells (OPCs) as appropriate model cells to pinpoint the mechanism of the progress of neurodegenerative disorders. In the present study, we focused on the therapeutic role of osteopontin (OPN), a secreted glycosylated phosphoprotein, involved in a number of physiological events including bone formation and remodeling, immune responses, and tumor progression. Protective role of OPN, as a negative regulator of tumorigenesis, has already been clarified. Human embryonic stem cell-derived OPCs were pretreated with OPN before induction of apoptosis by H2O2. Data indicated that OPN prohibited cell death and enhanced OPC viability. This effect is achieved through reduction of apoptosis and induction of anti-apoptosis markers. In addition OPN induces expression of several integrin subunits, responsible for OPN interaction. Notably, our findings showed that expression of αV β1/β3/β5 and β8 integrins increased in response to OPN, while treatment with H2O2 down-regulated αV β1/β5 and β8 integrins expression significantly. In conclusion, OPN may act via αV integrin signaling and trigger suppression of P53-dependent apoptotic cascades. Therefore OPN therapy may be considered as a feasible process to prevent progress of neurodegenerative diseases in human.

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Abbreviations

ANOVA:

One-way analysis of variance

bFGF:

Basic fibroblast growth factor

CNS:

Central nervous system

EBs:

Embryoid bodies

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

FITC:

Fluorescein isothiocyanate

hESC:

Human embryonic stem cell

Lam:

Laminin

MBP:

Myelin basic protein

MS:

Multiple sclerosis

OLs:

Oligodendrocytes

OPCs:

Oligodendrocyte progenitor cells

OPN:

Osteopontin

PBS:

Phosphate-buffered saline

PDGF:

Platelet-derived growth factor

PLL:

Poly-l-laminin

RA:

Retinoic acid

RGD:

Arg–Gly–Asp

ROS:

Reactive oxygen species

RT-qPCR:

Real-time quantitative PCR

SEM:

Standard error of mean

TRITC:

Tetramethyl rhodamine isothiocyanate

References

  • Albertsson AM, Zhang X, Leavenworth J, Bi D, Nair S, Qiao L, Hagberg H, Mallard C, Cantor H, Wang X (2014) The effect of osteopontin and osteopontin-derived peptides on preterm brain injury. J Neuroinflamm 11:197

    Article  Google Scholar 

  • Baud O, Greene AE, Li J, Wang H, Volpe JJ, Rosenberg PA (2004) Glutathione peroxidase-catalase cooperativity is required for resistance to hydrogen peroxide by mature rat oligodendrocytes. J Neurosci 24:1531–1540

    Article  CAS  PubMed  Google Scholar 

  • Behera R, Kumar V, Lohite K, Karnik S, Kundu GC (2009) Activation of JAK2/STAT3 signaling by osteopontin promotes tumor growth in human breast cancer cells. Carcinogenesis 31:192–200

    Article  PubMed  Google Scholar 

  • Buchet D, Baron-Van Evercooren A (2009) In search of human oligodendroglia for myelin repair. Neurosci Lett 456:112–119

    Article  CAS  PubMed  Google Scholar 

  • Burdo TH, Wood MR, Fox HS (2007) Osteopontin prevents monocyte recirculation and apoptosis. J Leukoc Biol 81:1504–1511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dash P (1994) Apoptosis; basic medical sciences. St.George’s University of London, London

    Google Scholar 

  • Denhardt DT, Noda M, O’Regan AW, Pavlin D, Berman JS (2001) Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival. J Clin Invest 107:1055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dhib-Jalbut S (2007) Pathogenesis of myelin/oligodendrocyte damage in multiple sclerosis. Neurology 68:S13–S21

    Article  CAS  PubMed  Google Scholar 

  • Geissinger E, Weisser C, Fischer P, Schartl M, Wellbrock C (2002) Autocrine stimulation by osteopontin contributes to antiapoptotic signalling of melanocytes in dermal collagen. Cancer Res 62:4820–4828

    CAS  PubMed  Google Scholar 

  • Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140:918–934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirrlinger J, Resch A, Gutterer JM, Dringen R (2002) Oligodendroglial cells in culture effectively dispose of exogenous hydrogen peroxide: comparison with cultured neurones, astroglial and microglial cells. J Neuroche 82:635–644

    Article  CAS  Google Scholar 

  • Hsu KH, Tsai HW, Lin PW, Hsu YS, Lu PJ, Shan YS (2014) Anti-apoptotic effects of osteopontin through the up-regulation of Mcl-1 in gastrointestinal stromal tumors. World J Surg Oncol 12:189

    Article  PubMed  PubMed Central  Google Scholar 

  • Hur EM, Youssef S, Haws ME, Zhang SY, Sobel RA, Steinman L (2007) Osteopontin-induced relapse and progression of autoimmune brain disease through enhanced survival of activated T cells. Nat Immunol 8:74–83

    Article  CAS  PubMed  Google Scholar 

  • Kajabadi NS, Ghoochani A, Peymani M, Ghaedi K, Kiani-Esfahani A, Hashemi MS, Nasr-Esfahani MH, Baharvand H (2015) The synergistic enhancement of cloning efficiency in individualized human pluripotent stem cells by peroxisome proliferative-activated receptor-γ (PPARγ) activation and rho-associated kinase (ROCK) inhibition. J Biol Chem 290(43):26303–26313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanduc D, Mittelman A, Serpico R, Sinigaglia E, Sinha AA, Natale C, Santacroce R, Di Corcia MG, Lucchese A, Dini L, Pani P, Santacroce S, Simone S, Bucci R, Farber E (2002) Cell death: apoptosis versus necrosis. Int J Oncol 21:165–170

    CAS  PubMed  Google Scholar 

  • Kim HJ, Lee HJ, Jun JI, Oh Y, Choi SG, Kim H, Chung CW, Kim IK, Park IS, Chae HJ, Kim HR, Jung YK (2009) Intracellular cleavage of osteopontin by caspase-8 modulates hypoxia/reoxygenation cell death through p53. Proc Natl Acad Sci U S A 106(36):15326–15331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Merrill J, Pu S.-F, Khorkova O, Ji Z, Camacho F, Busch S, Wang M, Chen T, Dinerstein, R, Yao Z (2003) Osteopontin, oligodendrocytes and myelination. Google Patents

  • Milner R, Ffrench-Constant C (1994) A developmental analysis of oligodendroglial integrins in primary cells: changes in alpha v-associated beta subunits during differentiation. Development 120:3497–3506

    CAS  PubMed  Google Scholar 

  • Miron VE, Kuhlmann T, Antel JP (2011) Cells of the oligodendroglial lineage, myelination, and remyelination. Biochim Biophys Acta 1812:184–193

    Article  CAS  PubMed  Google Scholar 

  • Mouzannar R, Miric SJ, Wiggins RC, Konat GW (2001) Hydrogen peroxide induces rapid digestion of oligodendrocyte chromatin into high molecular weight fragments. Neurochem Int 38:9–15

    Article  CAS  PubMed  Google Scholar 

  • O’Meara RW, Michalski JP, Kothary R (2010) Integrin signaling in oligodendrocytes and its importance in CNS myelination. J Signal Transduct 2011:354091

    PubMed  PubMed Central  Google Scholar 

  • Peymani M, Ghaedi K, Hashemi MS, Ghoochani A, Kiani-Esfahani A, Nasr-Esfahani MH, Baharvand H (2017) Ameliorating the effect of pioglitazone on LPS-induced inflammation of human oligodendrocyte progenitor cells. Cell Mol Neurobiol. https://doi.org/10.1007/s10571-017-0500-6

    Google Scholar 

  • Polager S, Ginsberg D (2009) p53 and E2f: partners in life and death. Nat Rev Cancer 9:738–748

    Article  CAS  PubMed  Google Scholar 

  • Pouya A, Satarian L, Kiani S, Javan M, Baharvand H (2011) Human induced pluripotent stem cells differentiation into oligodendrocyte progenitors and transplantation in a rat model of optic chiasm demyelination. PLoS ONE 6:e27925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rabenstein M, Hucklenbroich J, Willuweit A, Ladwig A, Fink GR, Schroeter M, Langen KJ, Rueger MA (2015) Osteopontin mediates survival, proliferation and migration of neural stem cells through the chemokine receptor CXCR4. Stem Cell Res Ther 6:99

    Article  PubMed  PubMed Central  Google Scholar 

  • Scatena M, Almeida M, Chaisson ML, Fausto N, Nicosia RF, Giachelli CM (1998) NF-κB mediates αvβ3 integrin-induced endothelial cell survival. J Cell Biol 141:1083–1093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schordan S, Schordan E, Endlich K, Endlich N (2011) α V-Integrins mediate the mechanoprotective action of osteopontin in podocytes. Am J Physiol Renal Physiol 300:F119–F132

    Article  CAS  PubMed  Google Scholar 

  • Selvaraju R, Bernasconi L, Losberger C, Graber P, Kadi L, Avellana-Adalid V, Picard-Riera N, Baron Van Evercooren A, Cirillo R, Kosco-Vilbois M, Feger G, Papoian R, Boschert U (2004) Osteopontin is upregulated during in vivo demyelination and remyelination and enhances myelin formation in vitro. Mol Cell Neurosci 25:707–721

    Article  CAS  PubMed  Google Scholar 

  • Sodek J, Ganss B, McKee MD (2000) Osteopontin. Crit Rev Oral Biol Med 11:279–303

    Article  CAS  PubMed  Google Scholar 

  • Song G, Ming Y, Mao Y, Bao S, Ouyang G (2008) Osteopontin prevents curcumin-induced apoptosis and promotes survival through Akt activation via αvβ3 integrins in human gastric cancer cells. Exp Biol Med 233:1537–1545

    Article  CAS  Google Scholar 

  • Sorokin L (2010) The impact of the extracellular matrix on inflammation. Nat Rev Immunol 10:712–723

    Article  CAS  PubMed  Google Scholar 

  • Stangel M, Hartung HP (2002) Remyelinating strategies for the treatment of multiple sclerosis. Prog Neurobio 68:361–376

    Article  CAS  Google Scholar 

  • Watzlawik J, Warrington AE, Rodriguez M (2010) Importance of oligodendrocyte protection, BBB breakdown and inflammation for remyelination. Expert Rev Neurother 10:441–457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wittmann C, Chockley P, Singh SK, Pase L, Lieschke GJ, Grabher C (2012) Hydrogen peroxide in inflammation: messenger, guide, and assassin. Adv Hematol 2012:541471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zahed Panah M, Nikbakht M, Sajjadi SM, Rostami S, Norooznezhad AH, Kamranzadeh Fumani H, Ghavamzadeh A, Mohammadi S (2017) Anti-apoptotic effects of osteopontin via the up-regulation of AKT/mTOR/β-catenin loop in acute myeloid leukemia cells. Int J Hematol Oncol Stem Cell Res 11(2):148–157

    PubMed  PubMed Central  Google Scholar 

  • Zhao C, Fancy SP, French-Constant C, Franklin RJ (2008) Osteopontin is extensively expressed by macrophages following CNS demyelination but has a redundant role in remyelination. Neurobiol Dis 31:209–217

    Article  PubMed  Google Scholar 

  • Zhao C, Fancy SP, Franklin RJ, French-Constant C (2009) Up-regulation of oligodendrocyte precursor cell αV integrin and its extracellular ligands during central nervous system remyelination. J Neurosci Res 87:3447–3455

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank our colleagues for their association and helpful discussions in this study.

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Authors and Affiliations

  1. Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran

    Neda Mazaheri & Hamid Galehdari

  2. Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

    Maryam Peymani

  3. Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

    Kamran Ghaedi & Mohammad Hossein Nasr-Esfahani

  4. Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, 816513-1378, Iran

    Maryam Peymani, Kamran Ghaedi, Ali Ghoochani, Abbas Kiani-Esfahani & Mohammad Hossein Nasr-Esfahani

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  1. Neda Mazaheri
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  2. Maryam Peymani
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  3. Hamid Galehdari
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  4. Kamran Ghaedi
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Contributions

NM was involved in concept and design, acquisition, analysis and interpretation of data, and drafting of the manuscript. MP was involved in supervision, and contributed to the design of work, analysis, and interpretation of data, and drafted sections of manuscript. HG was involved in supervision and contributed to design of work. KG was involved in supervision, and contributed to the design of work, analysis, and interpretation of data, critical revision of the manuscript for important intellectual content, and finalized the manuscript. AG contributed to design the work. AKE was involved in acquisition of data and drafted sections of manuscript. MHNE was involved in supervision, and contributed to the design of work, administrative, technical, or material support.

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Correspondence to Kamran Ghaedi or Mohammad Hossein Nasr-Esfahani.

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Mazaheri, N., Peymani, M., Galehdari, H. et al. Ameliorating Effect of Osteopontin on H2O2-Induced Apoptosis of Human Oligodendrocyte Progenitor Cells. Cell Mol Neurobiol 38, 891–899 (2018). https://doi.org/10.1007/s10571-017-0563-4

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