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.
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Additional information
Received 11 July 2007; returned for revision 27 September 2007; received from final revision 15 January 2008; accepted by J. Di Battista 15 January 2008
Rights and permissions
About this article
Cite this article
Chowdhury, T.T., Salter, D.M., Bader, D.L. et al. 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. Inflamm. res. 57, 306–313 (2008). https://doi.org/10.1007/s00011-007-7126-y
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00011-007-7126-y