Novel Elements of the Chondrocyte Stress Response Identified Using an in Vitro Model of Mouse Cartilage Degradation

Journal of Proteome Research
Richard WilsonAmanda J Fosang

Abstract

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 degrada...Continue Reading

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Citations

Jul 6, 2018·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Troy WanandyMichael D Wiese
May 8, 2020·Human Reproduction Update·Avinash S GaikwadMoira K O'Bryan
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Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Alexander R OckenSarah Calve
May 21, 2021·Molecular and Cellular Neurosciences·Rachel A K AtkinsonAnna E King
Oct 1, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christopher J PanebiancoJames C Iatridis

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