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Effects of Curcumin (Diferuloylmethane) on Nuclear Factor κB Signaling in Interleukin-1β-Stimulated Chondrocytes

Authors

  • GUNDULA SCHULZE-TANZIL,

    1. Charité University Medical School Berlin, Campus Benjamin Franklin, Institute of Anatomy, Department of Cell and Neurobiology, D-14195 Berlin, Germany
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  • ALI MOBASHERI,

    1. Connective Tissue Research Group, Faculty of Veterinary Science, University of Liverpool, Liverpool L69 7ZJ, United Kingdom
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  • JUDITH SENDZIK,

    1. Charité University Medical School Berlin, Campus Benjamin Franklin, Institute of Anatomy, Department of Cell and Neurobiology, D-14195 Berlin, Germany
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  • THILO JOHN,

    1. Charité Medicine University Berlin, Campus Benjamin Franklin, Department for Trauma Surgery, D-12200 Berlin, Germany
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  • MEHDI SHAKIBAEI

    Corresponding author
    1. Charité University Medical School Berlin, Campus Benjamin Franklin, Institute of Anatomy, Department of Cell and Neurobiology, D-14195 Berlin, Germany
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Address for correspondence: Mehdi Shakibaei, Charité University Medical School Berlin, Institute of Anatomy, Department of Cell and Neurobiology, Campus Benjamin Franklin, Königin-Luise-Strasse 15, D-14195 Berlin, Germany. Voice: +49-30-8445-1916; fax: +49-30-8445-1916. e-mail: mehdi.shakibaei@charite.de

Abstract

Abstract: Curcumin (diferuloylmethane) is a nontoxic dietary pigment in tumeric and curry and a potent inhibitor of the common transcription factor Nuclear Factor κB (NF-κB) in several cell types. It is well established that some of the catabolic effects of the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α in osteoarthritis are regulated by the activation of NF-κB. Therefore, the aim of this study was to determine whether curcumin modifies the catabolic response of chondrocytes to IL-1β. Human articular chondrocytes were prestimulated with 10 ng/mL IL-1β for 0, 4, 8, 12, or 24 h and then cotreated with 50 μM curcumin for 0, 12, 24, 36, or 48 h. Synthesis of the cartilage-specific collagen type II and matrix-degrading enzyme matrix metalloproteinase-3 (MMP-3) was investigated in chondrocytes by Western blot analysis. Activation and nuclear translocation of NF-κB were observed by immunofluorescence microscopy. IL-1β induced a decrease in collagen type II and upregulation of MMP-3 in a time-dependent manner. Upregulation of MMP-3 was inhibited by curcumin in a time-dependent manner. In addition, IL-1β-induced a decrease in type II collagen, which was relieved by curcumin treatment. In response to IL-1β, NF-κB translocated to the nucleus, but translocation was inhibited by curcumin, as revealed by immunofluorescence microscopy. Taken together, these results confirmed an IL-1β-mediated upregulation of proinflammatory MMP-3 in chondrocytes via an NF-κB activation mechanism. Curcumin protected chondrocytes from the catabolic effects of IL-1β, such as MMP-3 upregulation, and interestingly also relieved cytokine-induced suppression of matrix protein synthesis. Therefore, curcumin antagonizes crucial catabolic effects of IL-1β signaling that are known to contribute to the pathogenesis of osteoarthritis.

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