New elements of the chondrocyte stress response identified in a mouse model of cartilage degradation

By Richard Wilson

University of Tasmania

 

This work is significant for several reasons. It is the first application of proteomics to investigate how chondrocytes respond to interleukin-1, a key inflammatory mediator in joint disease such as osteoarthritis, at the tissue level. This is important, as previous studies have used cells grown in monolayer cultures, which is associated with loss of the chondrocyte phenotype caused by dissociation from their native extracellular matrix environment.
We have expanded our understanding of how oxidative stress and protein misfolding are linked, by showing the production of proteins specifically induced by formation of non-native disulphide bonds (Manf and Creld2). In addition to other markers of oxidative stress, such as Sod2, Sod3, Atox1, Gstp and GsrA, a particularly novel finding was the identification of vanin-1 as a major product of IL-1 stimulated chondrocytes. This protein is emerging as a major potential drug target in a number of important human diseases ranging from malaria through to diabetes.
The study is also notable from the substantial level of validation, including proteomic analysis of cartilage from two mouse genotypes, parallel transcriptomic studies by microarray analysis and localization of protein expression by immunohistochemistry.

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