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Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation.

Mansukhani A, Ambrosetti D, Holmes G, Cornivelli L, Basilico C - J. Cell Biol. (2005)

Bottom Line: Wnt signals promote osteoblast function and regulate bone mass.Sox2 associates with beta-catenin in osteoblasts and can inhibit the activity of a Wnt responsive reporter plasmid through its COOH-terminal domain.Our results indicate that FGF signaling could control many aspects of osteoblast differentiation through induction of Sox2 and regulation of the Wnt-beta-catenin pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA. mansua01@med.nyu.edu

ABSTRACT
Activating mutations in fibroblast growth factor receptor 2 (FGFR2) cause several craniosynostosis syndromes by affecting the proliferation and differentiation of osteoblasts, which form the calvarial bones. Osteoblasts respond to FGF with increased proliferation and inhibition of differentiation. We analyzed the gene expression profiles of osteoblasts expressing FGFR2 activating mutations (C342Y or S252W) and found a striking down-regulation of the expression of many Wnt target genes and a concomitant induction of the transcription factor Sox2. Most of these changes could be reproduced by treatment of osteoblasts with exogenous FGF. Wnt signals promote osteoblast function and regulate bone mass. Sox2 is expressed in calvarial osteoblasts in vivo and we show that constitutive expression of Sox2 inhibits osteoblast differentiation and causes down-regulation of the expression of numerous Wnt target genes. Sox2 associates with beta-catenin in osteoblasts and can inhibit the activity of a Wnt responsive reporter plasmid through its COOH-terminal domain. Our results indicate that FGF signaling could control many aspects of osteoblast differentiation through induction of Sox2 and regulation of the Wnt-beta-catenin pathway.

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Related in: MedlinePlus

Real-time RT-PCR on time course of FGF. OB1 cells were treated with 10 ng/ml FGF1 for 1, 3, 6, 10, or 24 h. Each indicated cDNA was amplified by real-time PCR using specific primers and SYBR green for PCR product detection. The value of 100% was given to each OB1 untreated (0 h) sample (black bars). The experiment was performed in quadruplicate and the average ± SD is shown.
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fig2: Real-time RT-PCR on time course of FGF. OB1 cells were treated with 10 ng/ml FGF1 for 1, 3, 6, 10, or 24 h. Each indicated cDNA was amplified by real-time PCR using specific primers and SYBR green for PCR product detection. The value of 100% was given to each OB1 untreated (0 h) sample (black bars). The experiment was performed in quadruplicate and the average ± SD is shown.

Mentions: The down-regulation of the expression of Wnt target genes dlx2, engrailed-1, cadherin-11, wisp1, and wisp2 was confirmed by real-time RT-PCR analysis (Fig. 2). Fig. 2 also shows that Sox2 expression is strongly induced by 1 h of FGF treatment, before significant down-regulation of Wnt target genes.


Sox2 induction by FGF and FGFR2 activating mutations inhibits Wnt signaling and osteoblast differentiation.

Mansukhani A, Ambrosetti D, Holmes G, Cornivelli L, Basilico C - J. Cell Biol. (2005)

Real-time RT-PCR on time course of FGF. OB1 cells were treated with 10 ng/ml FGF1 for 1, 3, 6, 10, or 24 h. Each indicated cDNA was amplified by real-time PCR using specific primers and SYBR green for PCR product detection. The value of 100% was given to each OB1 untreated (0 h) sample (black bars). The experiment was performed in quadruplicate and the average ± SD is shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171836&req=5

fig2: Real-time RT-PCR on time course of FGF. OB1 cells were treated with 10 ng/ml FGF1 for 1, 3, 6, 10, or 24 h. Each indicated cDNA was amplified by real-time PCR using specific primers and SYBR green for PCR product detection. The value of 100% was given to each OB1 untreated (0 h) sample (black bars). The experiment was performed in quadruplicate and the average ± SD is shown.
Mentions: The down-regulation of the expression of Wnt target genes dlx2, engrailed-1, cadherin-11, wisp1, and wisp2 was confirmed by real-time RT-PCR analysis (Fig. 2). Fig. 2 also shows that Sox2 expression is strongly induced by 1 h of FGF treatment, before significant down-regulation of Wnt target genes.

Bottom Line: Wnt signals promote osteoblast function and regulate bone mass.Sox2 associates with beta-catenin in osteoblasts and can inhibit the activity of a Wnt responsive reporter plasmid through its COOH-terminal domain.Our results indicate that FGF signaling could control many aspects of osteoblast differentiation through induction of Sox2 and regulation of the Wnt-beta-catenin pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA. mansua01@med.nyu.edu

ABSTRACT
Activating mutations in fibroblast growth factor receptor 2 (FGFR2) cause several craniosynostosis syndromes by affecting the proliferation and differentiation of osteoblasts, which form the calvarial bones. Osteoblasts respond to FGF with increased proliferation and inhibition of differentiation. We analyzed the gene expression profiles of osteoblasts expressing FGFR2 activating mutations (C342Y or S252W) and found a striking down-regulation of the expression of many Wnt target genes and a concomitant induction of the transcription factor Sox2. Most of these changes could be reproduced by treatment of osteoblasts with exogenous FGF. Wnt signals promote osteoblast function and regulate bone mass. Sox2 is expressed in calvarial osteoblasts in vivo and we show that constitutive expression of Sox2 inhibits osteoblast differentiation and causes down-regulation of the expression of numerous Wnt target genes. Sox2 associates with beta-catenin in osteoblasts and can inhibit the activity of a Wnt responsive reporter plasmid through its COOH-terminal domain. Our results indicate that FGF signaling could control many aspects of osteoblast differentiation through induction of Sox2 and regulation of the Wnt-beta-catenin pathway.

Show MeSH
Related in: MedlinePlus