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Novel elements of the chondrocyte stress response identified using an in vitro model of mouse cartilage degradation


Wilson, R and Golub, SB and Rowley, L and Angelucci, C and Karpievitch, YV and Bateman, JF and Fosang, AJ, Novel elements of the chondrocyte stress response identified using an in vitro model of mouse cartilage degradation, Journal of Proteome Research, 15, (3) pp. 1033-1050. ISSN 1535-3907 (2016) [Refereed Article]

Copyright Statement

2016 American Chemical Society

DOI: doi:10.1021/acs.jproteome.5b01115


The destruction of articular cartilage in osteoarthritis involves chondrocyte dysfunction and imbalanced extracellular matrix (ECM) homeostasis. Pro-inflammatory cytokines such as interleukin-1α (IL-1α) contribute to osteoarthritis pathophysiology, but the effects of IL-1α on chondrocytes within their tissue microenvironment have not been fully evaluated. To redress this we used label-free quantitative proteomics to analyze the chondrocyte response to IL-1α within a native cartilage ECM. Mouse femoral heads were cultured with and without IL-1α, and both the tissue proteome and proteins released into the media were analyzed. New elements of the chondrocyte response to IL-1α related to cellular stress included markers for protein misfolding (Armet, Creld2, and Hyou1), enzymes involved in glutathione biosynthesis and regeneration (Gstp1, Gsto1, and Gsr), and oxidative stress proteins (Prdx2, Txn, Atox1, Hmox1, and Vnn1). Other proteins previously not associated with the IL-1α response in cartilage included ECM components (Smoc2, Kera, and Crispld1) and cysteine proteases (cathepsin Z and legumain), while chondroadherin and cartilage-derived C-type lectin (Clec3a) were identified as novel products of IL-1α-induced cartilage degradation. This first proteome-level view of the cartilage IL-1α response identified candidate biomarkers of cartilage destruction and novel targets for therapeutic intervention in osteoarthritis.

Item Details

Item Type:Refereed Article
Keywords:cartilage, proteomics, osteoarthritis, chondrocyte, oxidative stress
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Proteomics and intermolecular interactions (excl. medical proteomics)
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Wilson, R (Dr Richard Wilson)
UTAS Author:Karpievitch, YV (Dr Yuliya Karpievitch)
ID Code:106452
Year Published:2016
Web of Science® Times Cited:23
Deposited By:Central Science Laboratory
Deposited On:2016-02-10
Last Modified:2019-06-11

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