Effects of the Mycotoxin Nivalenol on Bovine Articular Chondrocyte Metabolism In Vitro
2014
Objective: Kashin-Beck Disease (KBD) is an endemic, age-related degenerative osteoarthropathy and its cause is
hypothesised to involve Fusarium mycotoxins. This study investigated the Fusarium mycotoxin Nivalenol (NIV) on the
metabolism of bovine articular chondrocytes in vitro.
Design: The effect 0.0–0.5 mg/ml NIV on transcript levels of types I and II collagen, aggrecan, matrix metalloproteinases
(MMPs), a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS) and the tissue inhibitors of MMPs
(TIMPs) was investigated using quantitative PCR. Amounts of sulphated glycosaminoglycans, MMPs and TIMPs were
assessed using the Dimethylmethylene Blue assay, gelatin zymography and reverse gelatin zymography respectively.
Cytoskeletal organisation was analysed using confocal microscopy and cytoskeletal gene and protein levels were measured
by quantitative PCR and Western blot analysis, respectively.
Results: NIV caused a dose-dependent increase in aggrecan transcription with a concomitant retention of sGAG in the cell
lysate. Furthermore, NIV significantly increased MMPs-2, -3 & -9, ADAMTS-4 and -5, and TIMP-2 and -3 transcript levels but
inhibited type I collagen, MMP 1 and TIMP 1 mRNA levels. NIV promoted extensive cytoskeletal network remodelling,
particularly with vimentin where a dose-dependent peri-nuclear aggregation occurred.
Conclusion: NIV exposure to chondrocytes decreased matrix deposition, whilst enhancing selective catabolic enzyme
production, suggesting its potential for induction of cellular catabolism. This NIV-induced extracellular matrix remodelling
may be due to extensive remodelling/disassembly of the cytoskeletal elements. Collectively, these findings support the
hypothesis that trichothecene mycotoxins, and in particular NIV, have the potential to induce matrix catabolism and
propagate the pathogenesis of KBD.
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