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Effects of the mycotoxin nivalenol on bovine articular chondrocyte metabolism in vitro.
PLoS One. 2014; 9(10):e109536.Plos

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 µg/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.

Authors+Show Affiliations

Department of Anesthesiology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Division of Pathophysiology and Repair, School of Biosciences, Cardiff University, Cardiff, United Kingdom.Arthritis Research UK Biomechanics and Bioengineering Centre, Cardiff University, Cardiff, United Kingdom; Division of Pathophysiology and Repair, School of Biosciences, Cardiff University, Cardiff, United Kingdom.Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, China.Division of Pathophysiology and Repair, School of Biosciences, Cardiff University, Cardiff, United Kingdom.Arthritis Research UK Biomechanics and Bioengineering Centre, Cardiff University, Cardiff, United Kingdom; Division of Pathophysiology and Repair, School of Biosciences, Cardiff University, Cardiff, United Kingdom.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25329658

Citation

Li, Siyuan, et al. "Effects of the Mycotoxin Nivalenol On Bovine Articular Chondrocyte Metabolism in Vitro." PloS One, vol. 9, no. 10, 2014, pp. e109536.
Li S, Blain EJ, Cao J, et al. Effects of the mycotoxin nivalenol on bovine articular chondrocyte metabolism in vitro. PLoS ONE. 2014;9(10):e109536.
Li, S., Blain, E. J., Cao, J., Caterson, B., & Duance, V. C. (2014). Effects of the mycotoxin nivalenol on bovine articular chondrocyte metabolism in vitro. PloS One, 9(10), e109536. https://doi.org/10.1371/journal.pone.0109536
Li S, et al. Effects of the Mycotoxin Nivalenol On Bovine Articular Chondrocyte Metabolism in Vitro. PLoS ONE. 2014;9(10):e109536. PubMed PMID: 25329658.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of the mycotoxin nivalenol on bovine articular chondrocyte metabolism in vitro. AU - Li,Siyuan, AU - Blain,Emma J, AU - Cao,Junling, AU - Caterson,Bruce, AU - Duance,Victor C, Y1 - 2014/10/15/ PY - 2014/05/19/received PY - 2014/09/10/accepted PY - 2014/10/21/entrez PY - 2014/10/21/pubmed PY - 2015/6/30/medline SP - e109536 EP - e109536 JF - PloS one JO - PLoS ONE VL - 9 IS - 10 N2 - 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 µg/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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25329658/Effects_of_the_mycotoxin_nivalenol_on_bovine_articular_chondrocyte_metabolism_in_vitro_ L2 - http://dx.plos.org/10.1371/journal.pone.0109536 DB - PRIME DP - Unbound Medicine ER -