HC-gp39 contributes to chondrocyte differentiation by inducing SOX9 and type II collagen expressions.
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.
Jacques
C
C
UMR 7079 CNRS, Physiology and Physiopathology Laboratory, University Paris 6, 7 quai St-Bernard, Paris, 75252 Cedex 5, France.
Recklies
A D
AD
Levy
A
A
Berenbaum
F
F
D054392:Adipokines; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D000071451:Chitinase-3-Like Protein 1; D019902:Chondrocytes / Q000378:metabolism*; D024043:Collagen Type II / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006609:High Mobility Group Proteins / Q000502:physiology*; D006801:Humans; D037102:Lectins; D051379:Mice; D055758:SOX9 Transcription Factor; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology*
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D024043:Collagen Type II; D006023:Glycoproteins; D006609:High Mobility Group Proteins; D037102:Lectins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C527933:Sox9 protein, mouse; D014157:Transcription Factors