C Jacques1, A D Recklies, A Levy, F Berenbaum. 1. UMR 7079 CNRS, Physiology and Physiopathology Laboratory, University Paris 6, 7 quai St-Bernard, Paris, 75252 Cedex 5, France.
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.
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, humancartilage 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.
Authors: Daniel J Hoover; Viola Zhu; Ru Chen; Kenneth Briley; Ken Briley; Pranela Rameshwar; Stanley Cohen; Frederick D Coffman Journal: PLoS One Date: 2013-05-09 Impact factor: 3.240
Authors: Mark J Dixon; Amit Nathubhai; Ole A Andersen; Daan M F van Aalten; Ian M Eggleston Journal: Org Biomol Chem Date: 2008-11-13 Impact factor: 3.876