title: Effects of dosage titration of methylprednisolone acetate and triamcinolone acetonide on interleukin-1-conditioned equine articular cartilage explants in vitro.
abstract: BACKGROUND
  Osteoarthritis is a frequent sequela of joint disease, especially with severe injuries or if attempts at therapy are unsuccessful. Negative and positive effects of corticosteroid treatment of articular cartilage have been demonstrated by in vitro and in vivo studies.
  
  
  OBJECTIVE
  To assess the metabolic effects of varying dosages of methylprednisolone acetate (MPA) and triamcinolone acetonide (TA) on interleukin-1alpha (IL-1) conditioned equine cartilage explants. Our hypothesis was that lower dosages of corticosteroids would be less detrimental to cartilage metabolism than higher dosages. TA would be less detrimental to cartilage metabolism than MPA.
  
  
  METHODS
  Treatment groups included articular cartilage explants with no IL-1 (control), IL-1 alone, and IL-1 plus 10, 5, 1 and 0.5 mg/ml MPA or 1.2, 0.6, 0.12 and 0.06 mg/ml TA. Explants were labelled with 35SO4 prior to the beginning and end of the experiment to assess glycosaminoglycan (GAG) degradation and synthesis, respectively. Total GAG content in media and explants and total cartilage DNA were also analysed.
  
  
  RESULTS
  MPA and TA reduced GAG synthesis compared to control and IL-1 alone. The highest dosage of MPA (10 mg/ml) reduced GAG synthesis less than lower dosages of MPA and all dosages of TA. Compared to IL-1 alone, all dosages of TA and lower dosages of MPA increased GAG degradation. MPA at 10 mg/ml reduced GAG degradation. Both MPA and TA increased media GAG content compared to control and IL-1 explants. Total cartilage GAGs were unchanged with MPA, but reduced with TA, compared with IL-1 alone. Total cartilage DNA was decreased with MPA and increased with TA compared to IL-1 and control explants.
  
  
  CONCLUSIONS
  MPA and TA did not counteract the negative effects of IL-1 and did not maintain cartilage metabolism at control levels. Lower dosages of MPA and TA were not less detrimental to cartilage metabolism than higher dosages. TA did not appear to be less harmful than MPA on cartilage metabolism. The results of this study differ from the findings of comparable in vivo studies.
  
  
  CONCLUSIONS
  The low numbers of horses used in this study limits extrapolation of these findings to the equine population; however, this study also questions the clinical relevance of this in vitro model.
authors.affiliation: Equine Orthopaedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Dechant
authors.forename: G M
authors.initials: GM
authors.lastname: Baxter
authors.forename: D D
authors.initials: DD
authors.lastname: Frisbie
authors.forename: G W
authors.initials: GW
authors.lastname: Trotter
authors.forename: C W
authors.initials: CW
authors.lastname: McIlwraith
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D046508:Culture Techniques; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006025:Glycosaminoglycans / Q000032:analysis / Q000378:metabolism*; D006734:Horse Diseases / Q000188:drug therapy; D006736:Horses; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077555:Methylprednisolone Acetate; D010003:Osteoarthritis / Q000188:drug therapy / Q000662:veterinary; D014222:Triamcinolone Acetonide / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D006025:Glycosaminoglycans; D007375:Interleukin-1; D000077555:Methylprednisolone Acetate; D004247:DNA; D014222:Triamcinolone Acetonide; D008775:Methylprednisolone