Novel Elements of the Chondrocyte Stress Response Identified Using an in Vitro Model of Mouse Cartilage Degradation
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 the...
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Published in | Journal of proteome research Vol. 15; no. 3; pp. 1033 - 1050 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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United States
American Chemical Society
04.03.2016
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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. |
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AbstractList | 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. |
Author | Bateman, John F Wilson, Richard Angelucci, Constanza Golub, Suzanne B Karpievitch, Yuliya V Fosang, Amanda J Rowley, Lynn |
AuthorAffiliation | Department of Pediatrics Department of Biochemistry and Molecular Biology Centre of Excellence in Plant Energy Biology Royal Children’s Hospital University of Melbourne University of Western Australia and Harry Perkins Institute of Medical Research Murdoch Childrens Research Institute University of Tasmania School of Physical Sciences Central Science Laboratory |
AuthorAffiliation_xml | – name: Royal Children’s Hospital – name: Murdoch Childrens Research Institute – name: School of Physical Sciences – name: University of Melbourne – name: University of Western Australia and Harry Perkins Institute of Medical Research – name: Centre of Excellence in Plant Energy Biology – name: University of Tasmania – name: Central Science Laboratory – name: Department of Pediatrics – name: Department of Biochemistry and Molecular Biology |
Author_xml | – sequence: 1 givenname: Richard surname: Wilson fullname: Wilson, Richard email: richard.wilson@utas.edu.au – sequence: 2 givenname: Suzanne B surname: Golub fullname: Golub, Suzanne B – sequence: 3 givenname: Lynn surname: Rowley fullname: Rowley, Lynn – sequence: 4 givenname: Constanza surname: Angelucci fullname: Angelucci, Constanza – sequence: 5 givenname: Yuliya V surname: Karpievitch fullname: Karpievitch, Yuliya V – sequence: 6 givenname: John F surname: Bateman fullname: Bateman, John F – sequence: 7 givenname: Amanda J surname: Fosang fullname: Fosang, Amanda J |
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SubjectTerms | Animals Cartilage, Articular - metabolism Cartilage, Articular - pathology Cells, Cultured Chondrocytes - metabolism Interleukin-1alpha - physiology Mice, Inbred C57BL Proteome - metabolism Stress, Physiological |
Title | Novel Elements of the Chondrocyte Stress Response Identified Using an in Vitro Model of Mouse Cartilage Degradation |
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