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.