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Mechanical Injury Potentiates Proteoglycan Catabolism Induced by Interleukin-6 With Soluble Interleukin-6 Receptor and Tumor Necrosis Factor α in Immature Bovine and Adult Human Articular Cartilage

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ARTHRITIS AND RHEUMATISM
卷 60, 期 10, 页码 2985-2996

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WILEY
DOI: 10.1002/art.24857

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  1. NIH [AR-45779]
  2. Arthritis Foundation

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Objective. Traumatic joint injury can damage cartilage and release inflammatory cytokines from adjacent joint tissue. The present study was undertaken to study the combined effects of compression injury, tumor necrosis factor a (TNF alpha), and interleukin-6 (IL-6) and its soluble receptor (sIL-6R) on immature bovine and adult human knee and ankle cartilage, using an in vitro model, and to test the hypothesis that endogenous IL-6 plays a role in proteoglycan loss caused by a combination of injury and TNFa. Methods. Injured or uninjured cartilage disks were incubated with or without TNFa and/or IL-6/sIL6R. Additional samples were preincubated with an IL-6-blocking antibody Fab fragment and subjected to injury and TNFa treatment. Treatment effects were assessed by histologic analysis, measurement of glycos-aminoglycan (GAG) loss, Western blot to determine proteoglycan degradation, zymography, radiolabeling to determine chondrocyte biosynthesis, and Western blot and enzyme-linked immunosorbent assay to determine chondrocyte production of IL-6. Results. In bovine cartilage samples, injury combined with TNF alpha and IL-6/sIL-6R exposure caused the most severe GAG loss. Findings in human knee and ankle cartilage were strikingly similar to those in bovine samples, although in human ankle tissue, the GAG loss was less severe than that observed in human knee tissue. Without exogenous IL-6/sIL-6R, injury plus TNF alpha exposure up-regulated chondrocyte production of IL-6, but incubation with the IL-6-blocking Fab significantly reduced proteoglycan degradation. Conclusion. Our findings indicate that mechanical injury potentiates the catabolic effects of TNF alpha and IL-6/sIL-6R in causing proteoglycan degradation in human and bovine cartilage. The temporal and spatial evolution of degradation suggests the importance of transport of biomolecules, which may be altered by overload injury. The catabolic effects of injury plus TNF alpha appeared partly due to endogenous IL-6, since GAG loss was partially abrogated by an IL-6-blocking Fab.

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