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Autocrine Fibroblast Growth Factor 18 Mediates Dexamethasone-Induced Osteogenic Differentiation of Murine Mesenchymal Stem Cells

Hamidouche, Zahia; Fromigue, Olivia; Nuber, Ulrike LU ; Vaudin, Pascal; Pages, Jean-Christophe; Ebert, Regina; Jakob, Franz; Miraoui, Hichem and Marie, Pierre J. (2010) In Journal of Cellular Physiology 224(2). p.509-515
Abstract
The potential of mesenchymal stem cells (MSC) to differentiate into functional bone forming cells provides an important tool for bone regeneration. The identification of factors capable of promoting osteoblast differentiation in MSCs is therefore critical to enhance the osteogenic potential of MSCs. Using microarray analysis combined with biochemical and molecular approach, we found that FGF18, a member of the FGF family, is upregulated during osteoblast differentiation induced by dexamethasone in murine MSCs. We showed that overexpression of FGF18 by lentiviral (LV) infection, or treatment of MSCs with recombinant human (rh)FGF18 increased the expression of the osteoblast specific transcription factor Runx2, and enhanced osteoblast... (More)
The potential of mesenchymal stem cells (MSC) to differentiate into functional bone forming cells provides an important tool for bone regeneration. The identification of factors capable of promoting osteoblast differentiation in MSCs is therefore critical to enhance the osteogenic potential of MSCs. Using microarray analysis combined with biochemical and molecular approach, we found that FGF18, a member of the FGF family, is upregulated during osteoblast differentiation induced by dexamethasone in murine MSCs. We showed that overexpression of FGF18 by lentiviral (LV) infection, or treatment of MSCs with recombinant human (rh)FGF18 increased the expression of the osteoblast specific transcription factor Runx2, and enhanced osteoblast phenotypic marker gene expression and in vitro osteogenesis. Molecular silencing using lentiviral shRNA demonstrated that downregulation of FGFR1 or FGFR2 abrogated osteoblast gene expression induced by either LV-FGF18 or rhFGF18, indicating that FGF18 enhances osteoblast differentiation in MSCs via activation of FGFR1 or FGFR2 signaling. Biochemical and pharmacological analyses showed that the induction of phenotypic osteoblast markers by LV-FGF18 is mediated by activation of ERK1/2-MAPKs and PI3K signaling in MSCs. These results reveal that FGF18 is an essential autocrine positive regulator of the osteogenic differentiation program in murine MSCs and indicate that osteogenic differentiation induced by FGF18 in MSCs is triggered by FGFR1/FGFR2-mediated ERK1/2-MAPKs and PI3K signaling. J. Cell. Physiol. 224: 509-515, 2010. (C) 2010 Wiley-Liss, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cellular Physiology
volume
224
issue
2
pages
509 - 515
publisher
John Wiley & Sons
external identifiers
  • wos:000279418600027
  • scopus:77953632883
ISSN
1097-4652
DOI
10.1002/jcp.22152
language
English
LU publication?
yes
id
10758a48-550f-4fc5-b318-7f1762f849f6 (old id 1629063)
date added to LUP
2010-07-22 11:29:12
date last changed
2018-05-29 11:47:58
@article{10758a48-550f-4fc5-b318-7f1762f849f6,
  abstract     = {The potential of mesenchymal stem cells (MSC) to differentiate into functional bone forming cells provides an important tool for bone regeneration. The identification of factors capable of promoting osteoblast differentiation in MSCs is therefore critical to enhance the osteogenic potential of MSCs. Using microarray analysis combined with biochemical and molecular approach, we found that FGF18, a member of the FGF family, is upregulated during osteoblast differentiation induced by dexamethasone in murine MSCs. We showed that overexpression of FGF18 by lentiviral (LV) infection, or treatment of MSCs with recombinant human (rh)FGF18 increased the expression of the osteoblast specific transcription factor Runx2, and enhanced osteoblast phenotypic marker gene expression and in vitro osteogenesis. Molecular silencing using lentiviral shRNA demonstrated that downregulation of FGFR1 or FGFR2 abrogated osteoblast gene expression induced by either LV-FGF18 or rhFGF18, indicating that FGF18 enhances osteoblast differentiation in MSCs via activation of FGFR1 or FGFR2 signaling. Biochemical and pharmacological analyses showed that the induction of phenotypic osteoblast markers by LV-FGF18 is mediated by activation of ERK1/2-MAPKs and PI3K signaling in MSCs. These results reveal that FGF18 is an essential autocrine positive regulator of the osteogenic differentiation program in murine MSCs and indicate that osteogenic differentiation induced by FGF18 in MSCs is triggered by FGFR1/FGFR2-mediated ERK1/2-MAPKs and PI3K signaling. J. Cell. Physiol. 224: 509-515, 2010. (C) 2010 Wiley-Liss, Inc.},
  author       = {Hamidouche, Zahia and Fromigue, Olivia and Nuber, Ulrike and Vaudin, Pascal and Pages, Jean-Christophe and Ebert, Regina and Jakob, Franz and Miraoui, Hichem and Marie, Pierre J.},
  issn         = {1097-4652},
  language     = {eng},
  number       = {2},
  pages        = {509--515},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Cellular Physiology},
  title        = {Autocrine Fibroblast Growth Factor 18 Mediates Dexamethasone-Induced Osteogenic Differentiation of Murine Mesenchymal Stem Cells},
  url          = {http://dx.doi.org/10.1002/jcp.22152},
  volume       = {224},
  year         = {2010},
}