Related Experiment Video

Updated: Aug 22, 2026

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
08:43

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Published on: May 31, 2016

P253R fibroblast growth factor receptor-2 mutation induces RUNX2 transcript variants and calvarial osteoblast

Tiziano Baroni1, Paolo Carinci, Cinzia Lilli

  • 1Institute of Histology and General Embryology, University of Perugia, Perugia, Italy.

Journal of Cellular Physiology
|September 25, 2004
PubMed

Insights

Fibroblast growth factor receptor 2 (FGFR2) mutations in Apert syndrome lead to altered osteoblast function. FGF2 signaling is dysregulated, impacting extracellular matrix turnover and cell behavior.

Area of Science:

  • Molecular biology
  • Cell biology
  • Genetics

Background:

  • Fibroblast growth factor 2 (FGF2) signaling is crucial for skeletal development.
  • Mutations in fibroblast growth factor receptor 2 (FGFR2) cause craniosynostosis, including Apert syndrome.
  • Understanding FGFR2 mutations' cellular effects is vital for craniosynostosis research.

Purpose of the Study:

  • To investigate cellular phenotype changes in Apert patient osteoblasts.
  • To evaluate the impact of FGF2 on these cells.
  • To elucidate the FGF2 signaling pathway in Apert syndrome.

Main Methods:

  • In vitro study using calvarial osteoblasts from Apert patients (FGFR2 P253R mutation) and wild-type controls.
  • Analysis of gene expression (osteocalcin, RUNX2, MMP-13) and protein secretion (fibronectin, collagen).
  • Assessment of enzyme activities, receptor expression, and signal transduction pathways (Grb2 phosphorylation).

Main Results:

  • Apert osteoblasts showed down-regulated osteocalcin mRNA, altered RUNX2 splicing, and increased FGF2 secretion.
  • Increased total protein synthesis and fibronectin/collagen secretion, with decreased protease/glycosidase activity and MMP-13 transcription.
  • FGF2 addition modulated these changes; elevated FGF2 receptor activity and Grb2 signaling were observed, reduced by FGF2 stimulation.

Conclusions:

  • Apert osteoblasts exhibit increased constitutive FGFR2 activity.
  • An autocrine FGF2 loop likely modulates Apert osteoblast behavior.
  • Findings provide insights into craniosynostosis pathogenesis and potential therapeutic targets.

More Related Videos

Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis07:26

Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis

Published on: April 1, 2022

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells09:16

Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells

Published on: September 1, 2019

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...