p38MAPK mediates IL-1-induced down-regulation of aggrecan gene expression in human chondrocytes

  • Authors:
    • Jürgen Radons
    • Anja Katrin Bosserhoff
    • Susanne Grässel
    • Werner Falk
    • Thomas E.O. Schubert
  • View Affiliations

  • Published online on: April 1, 2006     https://doi.org/10.3892/ijmm.17.4.661
  • Pages: 661-668
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Abstract

The pleiotropic cytokine interleukin 1 (IL-1) is considered to be the principal inducer of mediators of cartilage degradation in both, osteoarthritis (OA) and rheumatoid arthritis (RA). IL-1 activates numerous signaling pathways involved in cartilage destruction and dedifferentiation of chondrocytes. In this study, we analyzed expression and functional effects of IL-1 in human chondrocytes. We found an IL-1-induced reduction in the expression of the cartilage specific proteoglycan aggrecan as an indicator for the IL-1-mediated dedifferentiation of chondrocytes. To block the IL-1-induced signaling pathways specifically, we incubated human chondrocytes and cartilage explants with IL-1 in the presence of different signal transduction inhibitors and analyzed their effect on aggrecan mRNA expression and IL-6 secretion. IL-6 has been found to act synergistically in the IL-1-induced suppression of the proteoglycan synthesis in chondrocytes. Our results led to the identification of p38MAPK and/or PI3K/JNK as being crucial for IL-1-induced IL-6 secretion by chondrocytes. IL-1-induced down-regulation of aggrecan expression was found to be mediated by p38MAPK and/or ERK1/2. The identification and characterization of these signaling pathways will enable us to develop new modulation strategies for therapeutic use in inflammatory joint diseases.

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April 2006
Volume 17 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Radons J, Bosserhoff AK, Grässel S, Falk W and Schubert TE: p38MAPK mediates IL-1-induced down-regulation of aggrecan gene expression in human chondrocytes. Int J Mol Med 17: 661-668, 2006
APA
Radons, J., Bosserhoff, A.K., Grässel, S., Falk, W., & Schubert, T.E. (2006). p38MAPK mediates IL-1-induced down-regulation of aggrecan gene expression in human chondrocytes. International Journal of Molecular Medicine, 17, 661-668. https://doi.org/10.3892/ijmm.17.4.661
MLA
Radons, J., Bosserhoff, A. K., Grässel, S., Falk, W., Schubert, T. E."p38MAPK mediates IL-1-induced down-regulation of aggrecan gene expression in human chondrocytes". International Journal of Molecular Medicine 17.4 (2006): 661-668.
Chicago
Radons, J., Bosserhoff, A. K., Grässel, S., Falk, W., Schubert, T. E."p38MAPK mediates IL-1-induced down-regulation of aggrecan gene expression in human chondrocytes". International Journal of Molecular Medicine 17, no. 4 (2006): 661-668. https://doi.org/10.3892/ijmm.17.4.661