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Natural chondroitin sulphates increase aggregation of proteoglycan complexes and decrease adamts-5 expression in IL-1β-treated chondrocytes
  1. Khadija Tahiri (khadija.tahiri{at}univ-paris5.fr)
  1. Inserm, UMR-S-747, Université Paris Descartes, Paris, F-75270, France
    1. Carla Korwin-Zmijowska (carla.korwin-zmijowska{at}univ-paris5.fr)
    1. Inserm, UMR-S-747, Université Paris Descartes, Paris, F-75270, France
      1. Pascal Richette (pascal.richette{at}lrb.ap-hop-paris.fr)
      1. Inserm, UMR-S-747, Université Paris Descartes, Paris, F-75270, France
        1. Florence Héraud (fheraud{at}laboratoires-genevrier.com)
        1. Laboratoires Genévrier, BP 47, F-06901 Sophia Antipolis, France
          1. Xavier Chevalier (xavier.chevalier{at}hmn.ap-hop-paris.fr)
          1. AP-HP, Groupe Hospitalier Henri Mondor, F-94000 Creteil, France
            1. Jean-François Savouret (jean-francois.savouret{at}univ-paris5.fr)
            1. Inserm, UMR-S-747, Université Paris Descartes, Paris, F-75270, France
              1. Marie-Thérèse Corvol (maite.corvol{at}univ-paris5.fr)
              1. Inserm, UMR-S-747, Université Paris Descartes, Paris, F-75270, France

                Abstract

                Objective: To assess the effect of natural chondroitin sulfate (CS) on the ability of neosynthesized sulfated proteoglycans (PGs) to aggregate in cultured chondrocytes treated with IL-1ß.

                Design: Primary cultured rabbit articular chondrocytes were treated or not with IL-1 alone or with concentrations of CS for 20 h. Neosynthesized PGs were labeled by incorporation of [35SO4]-sulfate and analyzed by chromatography on Sepharose 2B columns. Gelatinolytic activity was measured by zymography, and MMP1 mRNA level in chondrocytes underwent real-time PCR. ADAMTS-4 and -5 expression was analyzed by real-time PCR and western blotting.

                Results: The production of [35SO4]-labeled PGs was significantly increased with 10 μg/ml CS in the cellular pool rather than in the incubation medium. The addition of CS to IL-1ß-treated cells inhibited in part the disaggregation of sulfated PGs induced by IL-1ß. This inhibitory effect of CS is associated with a significant decrease in ADAMTS 5 expression, at both the mRNA and protein levels. No effect of CS was observed on IL-1ß-induced gelatinolytic activity, MMP1 mRNA expression or ADAMTS4 expression.

                Conclusion: CS increases the production of functional sulfated PGs in the direct environment of chondrocytes in vitro. This beneficial effect of CS in IL-1ß-treated cells is associated with decreased expression of ADAMTS 5.

                • ADAMTS
                • chondrocyte
                • chondroitin sulfate
                • proteoglycan aggregation

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