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

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-1? and dynamic compression.

Methods: dose-response studies were conducted under IL-1? conditions with either SB203580, SP600125, PDTC or curcumin. In separate experiments, constructs were treated with IL-1? 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-1? induced nitrite and PGE2 release in a dose-dependent manner. The inhibition of [3H]-thymidine incorporation by IL-1? was partially reversed with SB203580, SP600125 or curcumin, but not PDTC. In most cases, the inhibitors reduced 35SO4 incorporation with IL-1?. 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-?B signalling pathways are involved in the upregulation of NO and PGE2 release by IL-1?. Dynamic compression stimulates cell proliferation and proteoglycan synthesis in the presence of IL-1? and/or inhibitors of the MAPKs and NF?B and AP-1 signalling pathways. This experimental approach could provide valuable information for the biophysical/pharmacological treatment of OA

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ORCID for D.L. Bader: orcid.org/0000-0002-1208-3507

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