Inflammation Research

, Volume 57, Issue 7, pp 306–313

Signal transduction pathways involving p38 MAPK, JNK, NFκB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1β and dynamic compression

  • T. T. Chowdhury
  • D. M. Salter
  • D. L. Bader
  • D. A. Lee
Article

DOI: 10.1007/s00011-007-7126-y

Cite this article as:
Chowdhury, T.T., Salter, D.M., Bader, D.L. et al. Inflamm. res. (2008) 57: 306. doi:10.1007/s00011-007-7126-y

Abstract.

Objective and Design:

To examine whether inhibitors of the MAPK pathways will influence the response of bovine chondrocytes cultured in agarose constructs to IL-1β and dynamic compression.

Methods:

Dose-response studies were conducted under IL-1β conditions with either SB203580, SP600125, PDTC or curcumin. In separate experiments, constructs were treated with IL-1β and an appropriate concentration of inhibitor and subjected to 15% dynamic compression. Nitrite and PGE2 release, 35SO4 and [3H]-thymidine incorporation were subsequently measured using biochemical assays.

Results:

All inhibitors reduced the IL-1β induced nitrite and PGE2 release in a dose-dependent manner. The inhibition of [3H]-thymidine incorporation by IL-1β was partially reversed with SB203580, SP600125 or curcumin, but not PDTC. In most cases, the inhibitors reduced 35SO4 incorporation with IL-1β. For the mechanical loading studies, the inhibitors reduced the compression-induced inhibition of nitrite and PGE2 release and restored [3H]-thymidine and 35SO4 incorporation.

Conclusions:

The MAPK, AP-1 and NF-κB signalling pathways are involved in the upregulation of NO and PGE2 release by IL-1β. Dynamic compression stimulates cell proliferation and proteoglycan synthesis in the presence of IL-1β and/or inhibitors of the MAPKs and NFκB and AP-1 signalling pathways. This experimental approach could provide valuable information for the biophysical/pharmacological treatment of OA.

Keywords:

MAPKNitric oxidePGE2MechanotransductionCartilage

Copyright information

© Birkhaueser 2008

Authors and Affiliations

  • T. T. Chowdhury
    • 1
  • D. M. Salter
    • 2
  • D. L. Bader
    • 1
  • D. A. Lee
    • 1
  1. 1.School of Engineering and Materials ScienceQueen Mary University of LondonLondonUK
  2. 2.Queens Medical Research InstituteEdinburgh UniversityEdinburghUK