Effects of the mycotoxin nivalenol on bovine articular chondrocyte metabolism in vitro

Li, Siyuan, Blain, Emma Jane ORCID: https://orcid.org/0000-0001-8944-4254, Cao, Junling, Caterson, Bruce ORCID: https://orcid.org/0000-0001-6016-0661 and Duance, Victor Colin ORCID: https://orcid.org/0000-0002-7555-2016 2014. Effects of the mycotoxin nivalenol on bovine articular chondrocyte metabolism in vitro. PLoS ONE 9 (10) , e109536. 10.1371/journal.pone.0109536

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Abstract

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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Biosciences
Publisher:	Public Library of Science
ISSN:	1932-6203
Funders:	EPSRC, Arthritis Research UK, National Natural Science Foundation of China
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	10 September 2014
Last Modified:	15 May 2023 12:59
URI:	https://orca.cardiff.ac.uk/id/eprint/68291

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