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A pivotal role for protein kinase R in the oncostatin m and interleukin-1 induced catabolic phenotype in bovine articular cartilage chondrocytes

By Sophie Jane Gilbert, Victor Colin Duance and Deborah Jane Mason

Abstract

Introduction This study investigated whether treatment of articular cartilage chondrocytes with oncostatin m in combination with interleukin-1 could induce a degradative phenotype that was mediated through PKR. Materials and Methods High density monolayer cultures of full depth, bovine articular chondrocytes were treated with oncostatin-M (OSM; 10 ng/ml) and interleukin-1 (IL-1; 5 ng/ml) for 7-days. To inhibit the activation of PKR, a pharmacological inhibitor of PKR (Calbiochem, 1lM) was added to duplicate cultures. Media was analysed for MMPs (zymography) and cell extracts for type II collagen (Western blot) and gene expression (qPCR). Results Pro- and active MMP-9 and MMP-9 mRNA were significantly upregulated by OSM+IL-1. The expression of MMP-9 protein and mRNA was significantly reduced following PKR inhibition. The expression of ADAMTS-4 and ADAMTS-5 mRNA was upregulated significantly by OSM+IL-1. This upregulation was, in part, mediated through PKR. Treatment of chondrocytes with OSM+IL-1 resulted in a reduction in the amount of type II collagen detected, which could not be rescued by PKR inhibition. OSM+IL-1 treatment significantly reduced the expression of type II, XI, and IX, collagen, aggrecan, and sox9 mRNAs. Expression of these genes was reduced further when PKR was inhibited. OSM+IL-1 treatment resulted in an 11-fold increase in TNF-a mRNA which was, in part, mediated through the PKR pathway. Discussion This study suggests a novel role for the PKR signalling pathway in some of the well established degradative effects in articular cartilage that are induced by OSM, a member of the IL-6-family of cytokines when in combination with other pro-inflammatory cytokines such as IL-

Topics: QR Microbiology
Publisher: 'Wiley'
Year: 2009
DOI identifier: 10.1111/j.1365-2613.2008.00644.x
OAI identifier: oai:http://orca.cf.ac.uk:69049
Provided by: ORCA
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