Ameliorating Effect of Osteopontin on H2O2-Induced Apoptosis of Human Oligodendrocyte Progenitor Cells
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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.
KeywordsOPC OPN H2O2 Apoptosis
One-way analysis of variance
Basic fibroblast growth factor
Central nervous system
Epidermal growth factor
Human embryonic stem cell
Myelin basic protein
Oligodendrocyte progenitor cells
Platelet-derived growth factor
Reactive oxygen species
Real-time quantitative PCR
Standard error of mean
Tetramethyl rhodamine isothiocyanate
We thank our colleagues for their association and helpful discussions in this study.
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.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
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