期刊
JOURNAL OF PROTEOME RESEARCH
卷 15, 期 3, 页码 1033-1050出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.5b01115
关键词
cartilage; osteoarthritis; quantitative proteomics; chondrocyte; oxidative stress
资金
- National Health and Medical Research Council of Australia [1063133, 1002797, 491237]
- Australian Research Council [LE0775570]
- Australian Research Council [LE0775570] Funding Source: Australian Research Council
- National Health and Medical Research Council of Australia [1063133] Funding Source: NHMRC
The destruction of articular cartilage in osteoarthritis involves chondrocyte dysfunction and imbalanced extracellular matrix (ECM) homeostasis. Pro-inflammatory cytokines such as interleukin-1 alpha (IL-1 alpha) contribute to osteoarthritis pathophysiology, but the effects of IL-1 alpha 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-1 alpha within a native cartilage ECM. Mouse femoral heads were cultured with and without IL-1 alpha, and both the tissue proteome and proteins released into the media were analyzed. New elements of the chondrocyte response to IL-1 alpha 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-1 alpha 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-1 alpha-induced cartilage degradation. This first proteome-level view of the cartilage IL-1 alpha response identified candidate biomarkers of cartilage destruction and novel targets for therapeutic intervention in osteoarthritis.
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