Protein kinase R: A novel mediator of articular cartilage degradation in arthritis

Gilbert, Sophie Jane, Duance, Victor Colin ORCID: https://orcid.org/0000-0002-7555-2016 and Mason, Deborah Jane ORCID: https://orcid.org/0000-0002-8666-6094 2006. Protein kinase R: A novel mediator of articular cartilage degradation in arthritis. Current Rheumatology Reviews 2 (1) , pp. 9-21. 10.2174/157339706775697026

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Abstract

The protein kinase PKR is a key regulator of stress signalling pathways. We found that the PKR activating protein (PACT) is up-regulated in cartilage at the onset of osteoarthritis. PACT activates PKR in response to various cellular stresses such as TNF-α and IL-1. TNF-α also activates PKR via the sphingolipid second messenger, ceramide. Recent studies have shown that ceramide-induced activation of PKR inhibits protein synthesis as a prelude to cell death. TNF-α and ceramide stimulate cartilage degradation and we have demonstrated a role for PKR in TNF-α and ceramideinduced increases in the expression and activation of degradative enzymes in articular cartilage. The known role of PKR in cytokine-induced signalling pathways, together with our data showing cytokine regulation of PKR in chondrocytes, reveals a novel mechanism of cartilage degradation that may be important in the pathogenesis of arthritis. Elucidation of this pathway may enable more subtle control of cytokine-mediated degradation of cartilage and improve upon the efficacy of anti-TNF treatments in arthritis. This review will summarise the known activities of PKR and provide evidence for the involvement of this signalling pathway in cartilage breakdown.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Uncontrolled Keywords:	articular cartilage; arthritis; PKR; TNF-α; ceramide; matrix metalloproteinase
Publisher:	Ingentaconnect
ISSN:	1573-3971
Last Modified:	19 Oct 2022 10:50
URI:	https://orca.cardiff.ac.uk/id/eprint/25662

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