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Molecular silencing of Twist1 enhances osteogenic differentiation of murine mesenchymal stem cells: implication of FGFR2 signaling.
J Cell Biochem. 2010 Aug 01; 110(5):1147-54.JC

Abstract

The capacity of mesenchymal stem cells (MSCs) to differentiate into functional osteoblasts is tightly controlled by transcription factors that trigger osteoblast commitment and differentiation. The role of Twist1, a basic helix-loop-helix (bHLH) transcription factor, in osteogenic differentiation of MSCs remains unclear. Here we investigated the role of Twist1 in the osteogenic differentiation program of murine C3H10T1/2 mesenchymal cells. We showed that molecular silencing of Twist1 using short hairpin RNA (shRNA) expression moderately increased C3H10T1/2 cell proliferation and had no effect on cell survival. In contrast, Twist1 silencing enhanced osteoblast gene expression and matrix mineralization in vitro. Biochemical analyses revealed that Twist1 silencing increased the expression of FGFR2 protein level, which was reduced by a mutant Runx2. Consistent with this finding, Twist1 silencing increased ERK1/2 and PI3K signaling. Moreover, molecular or pharmacological inhibition of FGFR2 or of ERK1/2 and PI3K signaling partly abolished the increased osteoblast gene expression induced by Twist1 silencing in C3H10T1/2 cells. These results reveal that Twist1 silencing upregulates osteoblast differentiation of murine mesenchymal cells in part via activation of FGFR2 expression and downstream signaling pathways, which provides novel insights into the molecular signals by which this transcription factor regulates the osteogenic differentiation program in MSCs.

Authors+Show Affiliations

Laboratory of Osteoblast Biology and Pathology, Inserm U606, University Paris Diderot, Hôpital Lariboisiere, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20564211

Citation

Miraoui, Hichem, et al. "Molecular Silencing of Twist1 Enhances Osteogenic Differentiation of Murine Mesenchymal Stem Cells: Implication of FGFR2 Signaling." Journal of Cellular Biochemistry, vol. 110, no. 5, 2010, pp. 1147-54.
Miraoui H, Severe N, Vaudin P, et al. Molecular silencing of Twist1 enhances osteogenic differentiation of murine mesenchymal stem cells: implication of FGFR2 signaling. J Cell Biochem. 2010;110(5):1147-54.
Miraoui, H., Severe, N., Vaudin, P., Pagès, J. C., & Marie, P. J. (2010). Molecular silencing of Twist1 enhances osteogenic differentiation of murine mesenchymal stem cells: implication of FGFR2 signaling. Journal of Cellular Biochemistry, 110(5), 1147-54. https://doi.org/10.1002/jcb.22628
Miraoui H, et al. Molecular Silencing of Twist1 Enhances Osteogenic Differentiation of Murine Mesenchymal Stem Cells: Implication of FGFR2 Signaling. J Cell Biochem. 2010 Aug 1;110(5):1147-54. PubMed PMID: 20564211.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular silencing of Twist1 enhances osteogenic differentiation of murine mesenchymal stem cells: implication of FGFR2 signaling. AU - Miraoui,Hichem, AU - Severe,Nicolas, AU - Vaudin,Pascal, AU - Pagès,Jean-Christophe, AU - Marie,Pierre J, PY - 2010/6/22/entrez PY - 2010/6/22/pubmed PY - 2010/11/16/medline SP - 1147 EP - 54 JF - Journal of cellular biochemistry JO - J. Cell. Biochem. VL - 110 IS - 5 N2 - The capacity of mesenchymal stem cells (MSCs) to differentiate into functional osteoblasts is tightly controlled by transcription factors that trigger osteoblast commitment and differentiation. The role of Twist1, a basic helix-loop-helix (bHLH) transcription factor, in osteogenic differentiation of MSCs remains unclear. Here we investigated the role of Twist1 in the osteogenic differentiation program of murine C3H10T1/2 mesenchymal cells. We showed that molecular silencing of Twist1 using short hairpin RNA (shRNA) expression moderately increased C3H10T1/2 cell proliferation and had no effect on cell survival. In contrast, Twist1 silencing enhanced osteoblast gene expression and matrix mineralization in vitro. Biochemical analyses revealed that Twist1 silencing increased the expression of FGFR2 protein level, which was reduced by a mutant Runx2. Consistent with this finding, Twist1 silencing increased ERK1/2 and PI3K signaling. Moreover, molecular or pharmacological inhibition of FGFR2 or of ERK1/2 and PI3K signaling partly abolished the increased osteoblast gene expression induced by Twist1 silencing in C3H10T1/2 cells. These results reveal that Twist1 silencing upregulates osteoblast differentiation of murine mesenchymal cells in part via activation of FGFR2 expression and downstream signaling pathways, which provides novel insights into the molecular signals by which this transcription factor regulates the osteogenic differentiation program in MSCs. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/20564211/Molecular_silencing_of_Twist1_enhances_osteogenic_differentiation_of_murine_mesenchymal_stem_cells:_implication_of_FGFR2_signaling_ L2 - https://doi.org/10.1002/jcb.22628 DB - PRIME DP - Unbound Medicine ER -