title: The effects of mycotoxins and selenium deficiency on tissue-engineered cartilage.
abstract: OBJECTIVE
  To investigate the effects of 3 mycotoxins, deoxynivalenol (DON), nivalenol (NIV) and T-2 toxin, in the presence and absence of selenium (Se) on the metabolism of tissue-engineered cartilage to mimic conditions found in Kashin-Beck disease (KBD) environments.
  
  
  METHODS
  Chondrocytes were seeded onto bone matrix gelatin (BMG) to construct engineered cartilage. The 3 toxins were added to the culture media for 3 weeks followed by immunhistochemical analyses of collagens type II and X, aggrecan, matrix metalloproteinases 1 and 3 (MMP-1 and MMP-3), MMP inhibitors 1 and 3 (TIMP-1 and TIMP-3) and α(2) macroglobulin (α2M).
  
  
  RESULTS
  Type II collagen was decreased while type X collagen was increased in response to DON, NIV and T-2 toxin. Aggrecan was reduced by all 3 mycotoxins. Compared with the control, the 3 toxins decreased the expression of α2M, TIMP-1 and TIMP-3, and increased the expression of MMP-1 and MMP-3. Se could partially inhibit the effects of DON, NIV and T-2 toxins.
  
  
  CONCLUSIONS
  Under the low Se condition, the 3 mycotoxins produced procatabolic changes in cartilage resulting in the loss of aggrecan and type II collagen and promoted a hypertrophic phenotype of chondrocytes characterized by increasing type-X-collagen expression, enhancing the expression of MMPs, while weakening the TIMPs. Se could partially block the effects mentioned above. These results support the hypothesis that the combination of mycotoxin stress and Se deficiency would be the causative factors for KBD.
authors.affiliation: Institute of Endemic Diseases, Medical School, Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Minling
authors.initials: M
authors.lastname: Lu
authors.forename: Junling
authors.initials: J
authors.lastname: Cao
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Liu
authors.forename: Siyuan
authors.initials: S
authors.lastname: Li
authors.forename: Jinghong
authors.initials: J
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Zengtie
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jiayuan
authors.initials: J
authors.lastname: Liu
authors.forename: Mingxiu
authors.initials: M
authors.lastname: Luo
authors.forename: Jiali
authors.initials: J
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Bruce
authors.initials: B
authors.lastname: Caterson
mesh_terms: D053674:Aggrecans / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D057767:Kashin-Beck Disease / Q000209:etiology / Q000378:metabolism; D009183:Mycotoxins / Q000494:pharmacology*; D012643:Selenium / Q000172:deficiency / Q000494:pharmacology*; D013605:T-2 Toxin / Q000494:pharmacology*; D023822:Tissue Engineering; D014255:Trichothecenes / Q000494:pharmacology*
chemical_list: D053674:Aggrecans; D015415:Biomarkers; D024043:Collagen Type II; D009183:Mycotoxins; D014255:Trichothecenes; C038405:nivalenol; D012643:Selenium; D013605:T-2 Toxin; C007262:deoxynivalenol