HC-gp39 contributes to chondrocyte differentiation by inducing SOX9 and type II collagen expressions

Osteoarthritis Cartilage. 2007 Feb;15(2):138-46. doi: 10.1016/j.joca.2006.07.003. Epub 2006 Sep 1.

Abstract

Objective: The transcription factor SOX9 has been shown to be linked to chondrocyte differentiation and induction of type II collagen synthesis. Since the chitinase-like protein, human cartilage glycoprotein 39 (HC-gp39), can be expressed by articular chondrocytes and has been shown to enhance chondrocyte mitogenesis through MAP kinase and PI3 kinase-mediated signalling, we hypothesized that it may also promote synthesis of cartilage matrix components through induction of SOX9, utilizing similar signalling pathways.

Methods: Primary chondrocytes from neonatal mouse rib cartilage were exposed to purified HC-gp39. The response of the cells was evaluated in terms of SOX9 induction and synthesis of type II collagen. Signalling pathways activated following HC-gp9 exposure were analyzed by Western blotting of cell lysates with phosphorylation-specific antibodies as well as by using selective inhibitors.

Results: HC-gp39 induced both SOX9 and type II collagen synthesis. Similar results were observed for IGF-1. This process required signalling through both MAP kinase and PI3 kinase pathways resulting in rapid phosphorylation of ERK1/2 and AKT, respectively. Neither HC-gp39 nor IGF-1 induced activation of SAPK/JNK.

Conclusions: The effects of HC-gp39 on chondrocyte function suggest that this molecule may promote the maintenance or expression of a chondrocytic phenotype. Its expression in injured or degenerate cartilage could be related to the initial repair-response and increased matrix synthesis observed in osteoarthritic cartilage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines
  • Animals
  • Cell Culture Techniques / methods
  • Chitinase-3-Like Protein 1
  • Chondrocytes / metabolism*
  • Collagen Type II / genetics*
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Glycoproteins / physiology
  • High Mobility Group Proteins / physiology*
  • Humans
  • Lectins
  • Mice
  • SOX9 Transcription Factor
  • Signal Transduction / genetics*
  • Transcription Factors / physiology*

Substances

  • Adipokines
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Collagen Type II
  • Glycoproteins
  • High Mobility Group Proteins
  • Lectins
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Sox9 protein, mouse
  • Transcription Factors