title: Effects of the mycotoxin nivalenol on bovine articular chondrocyte metabolism in vitro.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Blain
authors.affiliation: Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Cao
authors.affiliation: Division of Pathophysiology and Repair, School of Biosciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Bruce
authors.initials: B
authors.lastname: Caterson
authors.affiliation: 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.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Duance
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D003470:Culture Media; D003599:Cytoskeleton / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D057767:Kashin-Beck Disease / Q000235:genetics / Q000473:pathology*; D008297:Male; D009183:Mycotoxins / Q000008:administration & dosage*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D014255:Trichothecenes / Q000008:administration & dosage*; D014746:Vimentin / Q000008:administration & dosage
chemical_list: D003470:Culture Media; D009183:Mycotoxins; D012333:RNA, Messenger; D014255:Trichothecenes; D014746:Vimentin; C038405:nivalenol