PMID- 25329658
OWN - NLM
STAT- MEDLINE
DCOM- 20150629
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 10
DP  - 2014
TI  - Effects of the mycotoxin nivalenol on bovine articular chondrocyte metabolism in 
      vitro.
PG  - e109536
LID - 10.1371/journal.pone.0109536 [doi]
LID - e109536
AB  - 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 microg/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.
FAU - Li, Siyuan
AU  - Li S
AD  - 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.
FAU - Blain, Emma J
AU  - Blain EJ
AD  - 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.
FAU - Cao, Junling
AU  - Cao J
AD  - Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong 
      University), Ministry of Education, Xi'an, China.
FAU - Caterson, Bruce
AU  - Caterson B
AD  - Division of Pathophysiology and Repair, School of Biosciences, Cardiff 
      University, Cardiff, United Kingdom.
FAU - Duance, Victor C
AU  - Duance VC
AD  - 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.
LA  - eng
GR  - Arthritis Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141015
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Culture Media)
RN  - 0 (Mycotoxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Trichothecenes)
RN  - 0 (Vimentin)
RN  - 5WOP02RM1U (nivalenol)
SB  - IM
MH  - Animals
MH  - Cartilage, Articular/*drug effects/metabolism
MH  - Cattle
MH  - Chondrocytes/*drug effects/metabolism
MH  - Culture Media
MH  - Cytoskeleton/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - In Vitro Techniques
MH  - Kashin-Beck Disease/genetics/*pathology
MH  - Male
MH  - Mycotoxins/*administration & dosage
MH  - Protein Biosynthesis
MH  - RNA, Messenger/biosynthesis
MH  - Trichothecenes/*administration & dosage
MH  - Vimentin/administration & dosage
PMC - PMC4198117
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/10/21 06:00
MHDA- 2015/06/30 06:00
PMCR- 2014/10/15
CRDT- 2014/10/21 06:00
PHST- 2014/05/19 00:00 [received]
PHST- 2014/09/10 00:00 [accepted]
PHST- 2014/10/21 06:00 [entrez]
PHST- 2014/10/21 06:00 [pubmed]
PHST- 2015/06/30 06:00 [medline]
PHST- 2014/10/15 00:00 [pmc-release]
AID - PONE-D-14-21549 [pii]
AID - 10.1371/journal.pone.0109536 [doi]
PST - epublish
SO  - PLoS One. 2014 Oct 15;9(10):e109536. doi: 10.1371/journal.pone.0109536. 
      eCollection 2014.