Novel elements of the Chondrocyte Stress Response identified using an in Vitro model of mouse cartilage degradation

R. Wilson, S.B. Golub, L. Rowley, C. Angelucci, Yuliya Karpievitch, J.F. Bateman, A.J. Fosang

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

© 2016 American Chemical Society. 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.
Original languageEnglish
Pages (from-to)1033-1050
Number of pages18
JournalJournal of Proteome Research
Volume15
Issue number3
Early online date21 Jan 2016
DOIs
Publication statusPublished - 4 Mar 2016

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