title: Novel Elements of the Chondrocyte Stress Response Identified Using an in Vitro Model of Mouse Cartilage Degradation.
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 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.
authors.affiliation: Central Science Laboratory, University of Tasmania , Hobart, Tasmania 7001, Australia.|Murdoch Childrens Research Institute, Royal Children's Hospital , Parkville, Melbourne, Victoria 3052, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: Wilson
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital , Parkville, Melbourne, Victoria 3052, Australia.|Department of Pediatrics, University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: Suzanne B
authors.initials: SB
authors.lastname: Golub
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital , Parkville, Melbourne, Victoria 3052, Australia.
authors.forename: Lynn
authors.initials: L
authors.lastname: Rowley
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital , Parkville, Melbourne, Victoria 3052, Australia.
authors.forename: Constanza
authors.initials: C
authors.lastname: Angelucci
authors.affiliation: School of Physical Sciences, University of Tasmania , Hobart, Tasmania 7001, Australia.|Centre of Excellence in Plant Energy Biology, University of Western Australia and Harry Perkins Institute of Medical Research , Perth, Western Australia 6009, Australia.
authors.forename: Yuliya V
authors.initials: YV
authors.lastname: Karpievitch
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital , Parkville, Melbourne, Victoria 3052, Australia.|Department of Biochemistry and Molecular Biology, University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Bateman
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital , Parkville, Melbourne, Victoria 3052, Australia.|Department of Pediatrics, University of Melbourne , Parkville, Victoria 3052, Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Fosang
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000502:physiology; D008810:Mice, Inbred C57BL; D020543:Proteome / Q000378:metabolism; D013312:Stress, Physiological
chemical_list: D053582:Interleukin-1alpha; D020543:Proteome
keywords: cartilage; chondrocyte; osteoarthritis; oxidative stress; quantitative proteomics