Concomitant inhibition of prolyl hydroxylases and ROCK initiates differentiation of mesenchymal stem cells and PC12 towards the neuronal lineage.
Biochemical and Biophysical Research Communications. 2008-12-01; 377(2): 400-406
DOI: 10.1016/j.bbrc.2008.09.145
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1. Biochem Biophys Res Commun. 2008 Dec 12;377(2):400-406. doi:
10.1016/j.bbrc.2008.09.145. Epub 2008 Oct 9.
Concomitant inhibition of prolyl hydroxylases and ROCK initiates differentiation
of mesenchymal stem cells and PC12 towards the neuronal lineage.
Pacary E(1), Petit E(2), Bernaudin M(2).
Author information:
(1)CERVOxy team “Hypoxia and cerebrovascular pathophysiology”, UMR CI-NAPS 6232
Université de Caen Basse-Normandie, Université Paris-Descartes, CEA, CNRS, Centre
CYCERON, Bd Henri Becquerel, BP5229, 14074 CAEN cedex, France. Electronic
address: .
(2)CERVOxy team “Hypoxia and cerebrovascular pathophysiology”, UMR CI-NAPS 6232
Université de Caen Basse-Normandie, Université Paris-Descartes, CEA, CNRS, Centre
CYCERON, Bd Henri Becquerel, BP5229, 14074 CAEN cedex, France.
This study demonstrates that a prolyl hydroxylase inhibitor, FG-0041, is able, in
combination with the ROCK inhibitor, Y-27632, to initiate differentiation of
mesenchymal stem cells (MSCs) into neuron-like cells. FG-0041/Y-27632
co-treatment provokes morphological changes into neuron-like cells, increases
neuronal marker expression and provokes modifications of cell cycle-related gene
expression consistent with a cell cycle arrest of MSC, three events showing the
engagement of MSC towards the neuronal lineage. Moreover, as we observed in our
previous studies with cobalt chloride and desferroxamine, the activation of HIF-1
by this prolyl hydroxylase inhibitor is potentiated by Y-27632 which could
explain at least in part the effect of this co-treatment on MSC neuronal
differentiation. In addition, we show that this co-treatment enhances neurite
outgrowth and tyrosine hydroxylase expression in PC12 cells. Altogether, these
results evidence that concomitant inhibition of prolyl hydroxylases and ROCK
represents a relevant protocol to initiate neuronal differentiation.
DOI: 10.1016/j.bbrc.2008.09.145
PMID: 18848521 [Indexed for MEDLINE]