Our previous analysis of the genes regulated in cartilage at the onset of spontaneous osteoarthritis in the guinea pig knee revealed up-regulation of the gene for protein kinase R (PKR)-activating protein (PACT), which encodes the cellular activator of the protein kinase, PKR. PACT and PKR are upstream components of a number of signal transduction and gene transcription pathways used by pro-inflammatory cytokines. We have investigated the role of PACT and PKR in articular cartilage degradation using cytokine treatment of bovine primary chondrocytes and cartilage explants. Tumour necrosis factor α increased expression of PACT protein after 3 h of treatment. Furthermore, increased phosphorylation of PKR and eukaryotic initiation factor 2-α was observed. The known role of PKR in cytokine-induced signalling pathways, together with our data showing cytokine regulation of PACT and PKR in chondrocytes, reveals a novel mechanism of cartilage degradation that may be important in the pathogenesis of arthritic diseases.

Keywords:
cartilage degradation, elF2-α, osteoarthritis, TNF-α, PKR, protein kinase R, PACT, protein kinase R-activating protein, OA, osteoarthritis, elF2-α, eukaryotic initiation factor 2-α, TNF-α, tumour necrosis factor α, IL-1, interleukin-1
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© 2002 Biochemical Society
2002
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