Related Experiment Video

Updated: Jun 14, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

FGFR3 down-regulates PTH/PTHrP receptor gene expression by mediating JAK/STAT signaling in chondrocytic cell line

Minqi Li1, Yukie Seki, Paulo H L Freitas

  • 1Center for Transdisciplinary Research, Niigata University, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Journal of Electron Microscopy
|April 2, 2010
PubMed

Insights

Fibroblast growth factor receptor 3 (FGFR3) reduces parathyroid hormone (PTH)/PTHrP receptor gene expression in chondrocytes. This occurs through the JAK/STAT signaling pathway, impacting chondrocyte proliferation and differentiation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Endocrinology

Background:

  • The parathyroid hormone (PTH)-related peptide (PTHrP) signaling axis, including the PTH/PTHrP receptor and fibroblast growth factor receptor 3 (FGFR3), is crucial for chondrocyte proliferation.
  • Indian hedgehog (IHH) gene expression in hypertrophic chondrocytes normally regulates PTH/PTHrP receptor signaling via a negative feedback loop.

Purpose of the Study:

  • To investigate how FGFR3 influences PTH/PTHrP receptor gene expression in chondrocytic cells.
  • To elucidate the signaling pathways involved in FGFR3-mediated regulation of PTH/PTHrP receptor expression.

Main Methods:

  • Utilized a FGFR3-transfected chondrocytic cell line (CFK2) to examine gene expression.
  • Assessed cell growth, apoptosis, and the activation of signaling pathways (JAK/STAT, MAPK).
  • Employed specific inhibitors (WHI-P131, SB203580, AG490) to probe signaling pathway involvement.

Main Results:

  • FGFR3 transfection in CFK2 cells led to reduced expression of PTH/PTHrP receptor (75% mRNA reduction) and PTHrP (50% reduction) genes.
  • Transfected cells exhibited decreased cell growth and increased apoptosis.
  • STAT1 nuclear localization indicated JAK/STAT pathway activation, and JAK3 inhibition partially reversed the FGFR3-induced reduction in PTH/PTHrP receptor gene expression.

Conclusions:

  • FGFR3 negatively regulates PTH/PTHrP receptor gene expression in chondrocytic cells.
  • The JAK/STAT signaling pathway, particularly involving JAK3, mediates this down-regulation.
  • These findings highlight a novel mechanism by which FGFR3 controls chondrocyte function and skeletal development.

More Related Videos

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...