Tyrosine kinase-type receptor ErbB4 in chondrocytes: interaction with connective tissue growth factor and

Kumiko Nawachi1, Miho Inoue, Satoshi Kubota

  • 1Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine and Dentistry, Japan.

FEBS Letters
|September 26, 2002
PubMed

Insights

Researchers identified ErbB4 as a receptor molecule involved in chondrocyte growth and differentiation. Its expression is regulated by connective tissue growth factor/hypertrophic chondrocyte-specific gene product (CTGF/Hcs24), suggesting a role in endochondral ossification.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Chondrocytes are crucial for endochondral ossification.
  • Identifying receptor molecules involved in chondrocyte growth and differentiation is essential for understanding skeletal development.
  • Connective tissue growth factor/hypertrophic chondrocyte-specific gene product (CTGF/Hcs24) is known to promote endochondral ossification.

Purpose of the Study:

  • To identify novel receptor molecules involved in chondrocyte growth and differentiation.
  • To investigate the role of ErbB4 in chondrogenesis.
  • To explore the relationship between ErbB4 and CTGF/Hcs24 in chondrocytes.

Main Methods:

  • Cloning of cDNA fragments from HCS-2/8 chondrocytic cells using tyrosine kinase-specific primers.
  • Analysis of ErbB4 mRNA expression in vitro and in vivo.
  • Investigating the effect of CTGF/Hcs24 on ErbB4 expression.

Main Results:

  • ErbB4 was identified as a receptor molecule expressed in chondrocytes.
  • Connective tissue growth factor/hypertrophic chondrocyte-specific gene product (CTGF/Hcs24) increased ErbB4 mRNA expression.
  • ErbB4 expression was detected throughout all stages of chondrocytic differentiation in vitro and in growth and articular cartilage in vivo.

Conclusions:

  • ErbB4 is expressed in chondrocytes and plays a role in chondrocytic growth and differentiation.
  • ErbB4 may function in conjunction with CTGF/Hcs24 to regulate endochondral ossification.
  • This study provides novel insights into the molecular mechanisms of chondrogenesis.

Related Concept Videos

Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Enzyme-linked Receptors01:13

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
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...
Growth of Cartilage and Bone Tissue01:27

Growth of Cartilage and Bone Tissue

Chondrocytes form a temporary cartilaginous model by dividing and secreting a thick gel-like extracellular matrix. Once the chondrocytes undergo programmed cell death, osteoblasts enter the site of the cartilaginous model. The process of replacing the temporary cartilaginous model with bone in an ordered manner is called endochondral ossification. In endochondral ossification, not all of the cartilage is replaced by bone tissue. Some cartilage that performs a protective and supportive function...
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...