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P253R fibroblast growth factor receptor-2 mutation induces RUNX2 transcript variants and calvarial osteoblast differentiation.
J Cell Physiol. 2005 Feb; 202(2):524-35.JC

Abstract

Unregulated fibroblast growth factor 2 (FGF2) signaling caused by mutations in the fibroblast growth factor receptor (FGFR2) leads to human craniosynostosis such as the Apert syndrome. In an in vitro control model of calvarial osteoblasts from Apert patients carrying the FGFR2 P253R mutation, we studied the changes in cellular phenotype and evaluated the effects of FGF2. Compared with wild-type controls, osteocalcin mRNA was down-regulated in Apert osteoblasts, Runt-related transcription factor-2 (RUNX2) mRNA was differentially spliced, and FGF2 secretion was greater. Total protein synthesis, fibronectin and type I collagen secretion were up-regulated, while protease and glycosidase activities and matrix metalloproteinase-13 (MMP-13) transcription were decreased, suggesting an altered ECM turnover. Adding FGF2 increased protease and glycosidase activities and down-regulated fibronectin and type I collagen secretion in Apert osteoblasts. High affinity FGF2 receptors were up-regulated in Apert osteoblasts and analysis of signal transduction showed elevated levels of Grb2 tyrosine phosphorylation and the Grb2-p85 beta association, which FGF2 stimulation strongly reduced. All together these findings suggest increased constitutive receptor activity in Apert mutant osteoblasts and an autocrine loop involving the FGF2 pathway in modulation of Apert osteoblast behavior.

Authors+Show Affiliations

Institute of Histology and General Embryology, University of Perugia, Perugia, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

15389579

Citation

Baroni, Tiziano, et al. "P253R Fibroblast Growth Factor Receptor-2 Mutation Induces RUNX2 Transcript Variants and Calvarial Osteoblast Differentiation." Journal of Cellular Physiology, vol. 202, no. 2, 2005, pp. 524-35.
Baroni T, Carinci P, Lilli C, et al. P253R fibroblast growth factor receptor-2 mutation induces RUNX2 transcript variants and calvarial osteoblast differentiation. J Cell Physiol. 2005;202(2):524-35.
Baroni, T., Carinci, P., Lilli, C., Bellucci, C., Aisa, M. C., Scapoli, L., Volinia, S., Carinci, F., Pezzetti, F., Calvitti, M., Farina, A., Conte, C., & Bodo, M. (2005). P253R fibroblast growth factor receptor-2 mutation induces RUNX2 transcript variants and calvarial osteoblast differentiation. Journal of Cellular Physiology, 202(2), 524-35.
Baroni T, et al. P253R Fibroblast Growth Factor Receptor-2 Mutation Induces RUNX2 Transcript Variants and Calvarial Osteoblast Differentiation. J Cell Physiol. 2005;202(2):524-35. PubMed PMID: 15389579.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - P253R fibroblast growth factor receptor-2 mutation induces RUNX2 transcript variants and calvarial osteoblast differentiation. AU - Baroni,Tiziano, AU - Carinci,Paolo, AU - Lilli,Cinzia, AU - Bellucci,Catia, AU - Aisa,Maria Cristina, AU - Scapoli,Luca, AU - Volinia,Stefano, AU - Carinci,Francesco, AU - Pezzetti,Furio, AU - Calvitti,Mario, AU - Farina,Antonio, AU - Conte,Carmela, AU - Bodo,Maria, PY - 2004/9/25/pubmed PY - 2005/2/19/medline PY - 2004/9/25/entrez SP - 524 EP - 35 JF - Journal of cellular physiology JO - J. Cell. Physiol. VL - 202 IS - 2 N2 - Unregulated fibroblast growth factor 2 (FGF2) signaling caused by mutations in the fibroblast growth factor receptor (FGFR2) leads to human craniosynostosis such as the Apert syndrome. In an in vitro control model of calvarial osteoblasts from Apert patients carrying the FGFR2 P253R mutation, we studied the changes in cellular phenotype and evaluated the effects of FGF2. Compared with wild-type controls, osteocalcin mRNA was down-regulated in Apert osteoblasts, Runt-related transcription factor-2 (RUNX2) mRNA was differentially spliced, and FGF2 secretion was greater. Total protein synthesis, fibronectin and type I collagen secretion were up-regulated, while protease and glycosidase activities and matrix metalloproteinase-13 (MMP-13) transcription were decreased, suggesting an altered ECM turnover. Adding FGF2 increased protease and glycosidase activities and down-regulated fibronectin and type I collagen secretion in Apert osteoblasts. High affinity FGF2 receptors were up-regulated in Apert osteoblasts and analysis of signal transduction showed elevated levels of Grb2 tyrosine phosphorylation and the Grb2-p85 beta association, which FGF2 stimulation strongly reduced. All together these findings suggest increased constitutive receptor activity in Apert mutant osteoblasts and an autocrine loop involving the FGF2 pathway in modulation of Apert osteoblast behavior. SN - 0021-9541 UR - https://www.unboundmedicine.com/medline/citation/15389579/P253R_fibroblast_growth_factor_receptor_2_mutation_induces_RUNX2_transcript_variants_and_calvarial_osteoblast_differentiation_ L2 - https://doi.org/10.1002/jcp.20148 DB - PRIME DP - Unbound Medicine ER -