title: Corticosteroids alter the differentiated phenotype of articular chondrocytes.
abstract: Experimental evidence suggests that recommended dosages of some corticosteroids used clinically as antiinflammatory agents for treating arthropathies damage articular cartilage, but low dosages may be chondroprotective. The purpose of this study was to evaluate how different concentrations of methylprednisolone affect chondrocyte function and viability. Articular cartilage and chondrocytes were obtained from young adult horses, 1.5-3.5 years of age. Corticosteroid-induced changes in collagen expression were studied at the transcriptional level by Northern blot analyses and at the translational level by measuring [3H]-proline incorporation into [3H]-hydroxyproline. Fibronectin mRNA splicing patterns were evaluated with ribonuclease protection assays. Cytotoxicity was studied using erythrosin B dye exclusion. Steady-state levels of type II procollagen mRNA decreased without concurrent changes in type I procollagen expression as the medium methylprednisolone concentrations were increased from 1 x 10(1) to 1 x 10(8) pg/ml, dropping below 10% of control values by 1 x 10(5) pg/ml. Cytotoxicity occurred as methylprednisolone levels were increased further from 1 x 10(8) to 1 x 10(9) pg/ml. Changes in total collagen (protein) synthesis were less pronounced, but also demonstrated significant suppression between 1 x 10(4) and 1 x 10(8) pg/ml. Corticosteroid-induced changes in fibronectin isoform levels were evaluated in articular cartilage samples without in vitro culture. The cartilage-specific (V + C)(-) isoform was suppressed in both normal and inflamed joints by a single intraarticular injection (0.1 mg/kg) of methylprednisolone. Combined, these data indicate that methylprednisolone suppresses matrix protein markers of chondrocytic differentiation. Decreased and altered chondrocyte expression of matrix proteins likely contributes to the pathogenesis of corticosteroid-induced cartilage degeneration.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Fubini
authors.forename: R J
authors.initials: RJ
authors.lastname: Todhunter
authors.forename: N
authors.initials: N
authors.lastname: Burton-Wurster
authors.forename: M
authors.initials: M
authors.lastname: Vernier-Singer
authors.forename: J N
authors.initials: JN
authors.lastname: MacLeod
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006736:Horses; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology*; D010641:Phenotype; D011347:Procollagen / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D011347:Procollagen; D012333:RNA, Messenger; D008776:Methylprednisolone Hemisuccinate