Related Experiment Video

Updated: May 17, 2026

A Rat Tibial Growth Plate Injury Model to Characterize Repair Mechanisms and Evaluate Growth Plate Regeneration Strategies
06:53

A Rat Tibial Growth Plate Injury Model to Characterize Repair Mechanisms and Evaluate Growth Plate Regeneration Strategies

Published on: July 4, 2017

Src and fibroblast growth factor 2 independently regulate signaling and gene expression induced by experimental

Fiona E Watt1, Heba M Ismail, Athanasios Didangelos

  • 1Kennedy Institute of Rheumatology, University of Oxford, 65 Aspenlea Road, London W6 8LH, UK. fiona.watt@kennedy.ox.ac.uk

Arthritis and Rheumatism
|November 6, 2012
PubMed
Abstract

Insights

Cartilage injury activates Src-like kinases, distinct from FGF signaling, which regulate inflammatory gene responses. This identifies a parallel pathway crucial for understanding cartilage damage and inflammation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Signaling

Background:

  • Articular cartilage injury can trigger complex cellular responses.
  • Fibroblast growth factor (FGF)-related signaling pathways are known mediators in cellular processes.
  • The role of other protein tyrosine kinases in cartilage injury response remains to be fully elucidated.

Purpose of the Study:

  • To determine if protein tyrosine kinases distinct from FGF signaling are activated by cartilage injury.
  • To investigate the contribution of these kinases to injury-induced gene expression changes.
  • To elucidate the signaling pathways involved in the immediate response to articular cartilage surface injury.

Main Methods:

  • Western blotting was used to assay phosphokinases and protein tyrosine phosphorylation in cartilage lysates.
  • Immunoprecipitation and mass spectrometry identified tyrosine-phosphorylated proteins and their associated kinases.
  • Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assessed messenger RNA induction in response to injury and inhibitor treatments.

Main Results:

  • Protein tyrosine phosphorylation and activation of MAPKs and IKK occurred within seconds of cartilage injury.
  • Focal adhesion kinase, paxillin, and cortactin were identified as substrates of Src family kinases.
  • Src family kinase inhibition blocked injury-induced tyrosine phosphorylation and differentially inhibited inflammatory gene induction, while FGF signaling blockade affected MAPK/IKK activation and a different gene subset.

Conclusions:

  • Articular cartilage surface injury activates Src-like kinases, MAPKs, and IKK, suggesting NF-κB activation.
  • FGF-2 contributes to MAPK/IKK activation but not Src-like signaling.
  • Src-like kinase signaling represents a parallel pathway to FGF signaling in regulating the inflammatory gene response to cartilage injury.

More Related Videos

Creation of a Knee Joint-on-a-Chip for Modeling Joint Diseases and Testing Drugs12:44

Creation of a Knee Joint-on-a-Chip for Modeling Joint Diseases and Testing Drugs

Published on: January 27, 2023

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Introduction to Fibroblasts01:09

Introduction to Fibroblasts

Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
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...
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...