title: Influence of corticosteroids on interleukin-1β-stimulated equine chondrocyte gene expression.
abstract: OBJECTIVE
  To compare the effects of triamcinolone acetonide (TA) and methylprednisolone acetate (MPA) on expression of selected chondrocyte genes in recombinant equine interleukin-1β (reIL-1β) stimulated articular cartilage explants.
  
  
  METHODS
  In vitro experiment.
  
  
  METHODS
  Horses (n = 6).
  
  
  METHODS
  Articular cartilage explants from 2- to 3- year-old horses were exposed to reIL-1β in the presence and absence of TA and MPA at 10(-7) and 10(-6) M. Resting levels of mRNA of anabolic and catabolic genes of chondrocyte origin were quantified using qPCR after 6- and 12-hour incubations. Genes of interest included aggrecan interglobular domain, aggrecan, and collagen II, matrix metalloproteinases 3 and 13 (MMP3, MMP 13), aggrecanase 1, tissue inhibitor of matrix metalloproteinases 1 and 2 (TIMP 1, TIMP 2), BCL 2, vascular endothelial growth factor, and cyclooxygenase 2 (COX 2).
  
  
  RESULTS
  IL-1β significantly influenced the expression of most transcripts. MPA and TA inhibited the induction of MMP 13 at 6 and 12 hours; an effect that was significant at 6 hours with MPA at 10(-7) M and TA at 10(-6) M. Similarly, COX 2 was induced by reIL-1β and MPA and TA significantly inhibited its upregulation. TIMP 2 expression was reduced by reIL-1β, an effect that was significantly abrogated by MPA and TA. There were no significant differences observed between glucocorticoids for any gene studied.
  
  
  CONCLUSIONS
  No differential effects of MPA or TA on chondrocytic gene expression were identified suggesting that any divergent influences of these glucocorticoids on chondrocyte metabolism are posttranslational.
authors.affiliation: Department of Large Animal, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA. caron@cvm.msu.edu
authors.forename: John P
authors.initials: JP
authors.lastname: Caron
authors.forename: Jeff C
authors.initials: JC
authors.lastname: Gandy
authors.forename: Michelle
authors.initials: M
authors.lastname: Schmidt
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Hauptman
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: Sordillo
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D053674:Aggrecans / Q000096:biosynthesis; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D024043:Collagen Type II / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects*; D006736:Horses; D053583:Interleukin-1beta / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077555:Methylprednisolone Acetate; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D014222:Triamcinolone Acetonide / Q000494:pharmacology*; D001613:beta 2-Microglobulin
chemical_list: D000305:Adrenal Cortex Hormones; D053674:Aggrecans; D024043:Collagen Type II; D053583:Interleukin-1beta; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D001613:beta 2-Microglobulin; D000077555:Methylprednisolone Acetate; D051546:Cyclooxygenase 2; D051722:ADAM Proteins; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D014222:Triamcinolone Acetonide; D008775:Methylprednisolone