Abstract
Degradation of collagen type II caused by pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) is one of the major pathological characteristics of osteoarthritis (OA). Dimethyl fumarate (DMF) is a medication approved by the US Food and Drug Administration (FDA) as an oral multiple sclerosis (MS) therapy. In this study, we found that DMF ameliorated collagen type II degradation by inhibiting the expression of MMP-1, MMP-3, and MMP-13 caused by TNF-α. Mechanistically, DMF attenuated MMPs expression by suppressing JAK/STAT3 pathway. These findings imply that DMF treatment might be a potential therapeutic strategy for chondroprotective therapy.
MeSH terms
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Cells, Cultured
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Chondrocytes / drug effects*
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Chondrocytes / immunology
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Chondrocytes / metabolism
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Collagen Type II / immunology*
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Collagen Type II / metabolism
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Dimethyl Fumarate
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Fumarates / pharmacology*
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Gene Expression Regulation / drug effects
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Humans
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Immunosuppressive Agents / pharmacology*
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Janus Kinase 2 / immunology
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Matrix Metalloproteinase 1 / genetics
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Matrix Metalloproteinase 1 / immunology
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Matrix Metalloproteinase 13 / genetics
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Matrix Metalloproteinase 13 / immunology
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Matrix Metalloproteinase 3 / genetics
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Matrix Metalloproteinase 3 / immunology
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Proteolysis
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STAT3 Transcription Factor / immunology
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Signal Transduction / drug effects
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Tumor Necrosis Factor-alpha / immunology*
Substances
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Collagen Type II
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Fumarates
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Immunosuppressive Agents
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STAT3 Transcription Factor
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Tumor Necrosis Factor-alpha
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Janus Kinase 2
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Matrix Metalloproteinase 13
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Matrix Metalloproteinase 3
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Matrix Metalloproteinase 1
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Dimethyl Fumarate