This title appears in the Scientific Report :
2015
Please use the identifier:
http://hdl.handle.net/2128/8973 in citations.
Please use the identifier: http://dx.doi.org/10.1186/s13287-015-0098-x in citations.
Osteopontin mediates survival, proliferation and migration of neural stem cells through the chemokine receptor CXCR4
Osteopontin mediates survival, proliferation and migration of neural stem cells through the chemokine receptor CXCR4
IntroductionOsteopontin (OPN) is a phosphoglycoprotein with important roles in tissue homeostasis, wound healing, immune regulation, and stress responses. It is expressed constitutively in the brain and upregulated during neuroinflammatory responses; for example, after focal cerebral ischemia. To da...
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Personal Name(s): | Rabenstein, M. |
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Hucklenbroich, J. / Willuweit, Antje / Ladwig, A. / Fink, Gereon Rudolf / Schroeter, M. / Langen, Karl-Josef / Rueger, M. A. (Corresponding author) | |
Contributing Institute: |
Physik der Medizinischen Bildgebung; INM-4 Kognitive Neurowissenschaften; INM-3 |
Published in: | Stem cell research & therapy, 6 (2015) 1, S. article 99 |
Imprint: |
London
BioMed Central
2015
|
PubMed ID: |
25998490 |
DOI: |
10.1186/s13287-015-0098-x |
Document Type: |
Journal Article |
Research Program: |
(Dys-)function and Plasticity |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.1186/s13287-015-0098-x in citations.
IntroductionOsteopontin (OPN) is a phosphoglycoprotein with important roles in tissue homeostasis, wound healing, immune regulation, and stress responses. It is expressed constitutively in the brain and upregulated during neuroinflammatory responses; for example, after focal cerebral ischemia. To date, its effects on neural stem cells (NSC) remain to be elucidated and are, accordingly, the subject of this study.MethodPrimary fetal rat NSC were cultured as homogenous monolayers and treated with different concentrations of OPN. Fundamental properties of NSC were assessed following OPN exposure, including proliferative activity, survival under oxidative stress, migration, and differentiation potential. To elucidate a putative action of OPN via the CXC chemokine receptor type 4 (CXCR4), the latter was blocked with AMD3100. To investigate effects of OPN on endogenous NSC in vivo, recombinant OPN was injected into the brain of healthy adult rats as well as rats subjected to focal cerebral ischemia. Effects of OPN on NSC proliferation and neurogenesis in the subventricular zone were studied immunohistochemically.ResultsOPN dose-dependently increased the number of NSC in vitro. As hypothesized, this effect was mediated through CXCR4. The increase in NSC number was due to both enhanced cell proliferation and increased survival, and was confirmed in vivo. Additionally, OPN dose-dependently stimulated the migration of NSC via CXCR4. Moreover, in the presence of OPN, differentiation of NSC led to a significant increase in neurogenesis both in vitro as well as in vivo after cerebral ischemia.ConclusionData show positive effects of OPN on survival, proliferation, migration, and neuronal differentiation of NSC. At least in part these effects were mediated via CXCR4. Results suggest that OPN is a promising substance for the targeted activation of NSC in future experimental therapies for neurological disorders such as stroke. |