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 inJournal of proteome research Vol. 15; no. 3; pp. 1033 - 1050
Main Authors Wilson, Richard, Golub, Suzanne B, Rowley, Lynn, Angelucci, Constanza, Karpievitch, Yuliya V, Bateman, John F, Fosang, Amanda J
Format Journal Article
LanguageEnglish
Published 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.
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
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– name: University of Melbourne
– name: University of Western Australia and Harry Perkins Institute of Medical Research
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  givenname: Richard
  surname: Wilson
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  givenname: Suzanne B
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/26794603$$D View this record in MEDLINE/PubMed
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Keywords chondrocyte
osteoarthritis
quantitative proteomics
oxidative stress
cartilage
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Snippet The destruction of articular cartilage in osteoarthritis involves chondrocyte dysfunction and imbalanced extracellular matrix (ECM) homeostasis....
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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
URI http://dx.doi.org/10.1021/acs.jproteome.5b01115
https://www.ncbi.nlm.nih.gov/pubmed/26794603
https://search.proquest.com/docview/1770883682
Volume 15
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