Volume 5 Supplement 3

3rd World Congress of the Global Arthritis Research Network (GARN): International Arthritis Summit

Open Access

Role of HC-gp39 in chondrogenesis: upregulation of SOX-9 expression by HC-gp39 in mouse chondrocytes

  • C Jacques1,
  • A Recklies2,
  • A Levy1,
  • A Labat1 and
  • F Berenbaum1
Arthritis Res Ther20035(Suppl 3):54

https://doi.org/10.1186/ar855

Published: 12 September 2003

Introduction

Increased levels of the chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) have been demonstrated in synovial fluids of patients with rheumatoid or osteoarthritis. Recently, this protein has emerged as a potential growth factor for synovial cells and chondrocytes, but little is known about its role in differentiation. The transcription factor SOX-9 has been demonstrated to be a master regulator of the differentiation of mesenchymal cells into chondrocytes.

Aim

We investigate the effects of two growth factors, insulin-like growth factor-I (IGF-I) and HC-gp39, on SOX-9 expression, and we sought to identify transduction signalling pathways involved in SOX-9 expression.

Methods

Expressions of SOX-9 and type II collagen were analysed in primary culture of mouse costochondral chondrocytes using Western blot analysis. Chondrocytes were stimulated by IGF-I and/or HC-gp39 during 24 hours. The kinetics with IGF-I and/or HC-gp39 (up to 60 min) was assessed with different antibodies against phosphorylated and nonphosphorylated forms of p38 MAPK, ERK1/2 MAPK, SAPK/JNK and AKT.

Results

IGF-I (25 ng/ml) and HC-gp39 (1 μg/ml) were found to markedly upregulate SOX-9 protein expression at 24 hours, which was in parallel with an increased expression of type II collagen protein. An IGF-I and HC-gp39 cotreatment showed an additive effect on SOX-9 protein expression. IGF-I and HC-gp39 were found to rapidly activate the phosphorylation of ERK1/2 MAPK and AKT (peak at 2 min), whereas p38 MAPK and SAPK/JNK pathways were not involved.

Conclusions

These results indicate that the expression of the gene for the master chondrogenic factor SOX-9 is stimulated by IGF-I and HC-gp39 in chondrocytes, and strongly suggest that this regulation is mediated by the ERK1/2 MAPK and AKT pathways. Because SOX-9 is essential for chondrocyte differentiation, we propose that HC-gp39 could be considered a novel actor involved in chondrogenesis.

Authors’ Affiliations

(1)
Department of Physiology and Physiopathology, UMR 7079 CNRS, University of Paris
(2)
Shriners Hospital for Children

Copyright

© The Author(s) 2003

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