Corticosteroids alter the differentiated phenotype of articular chondrocytes

Experimental evidence suggests that recommended dosages of some corticoster oids used clinically as antiinflammatory agents for treating arthropathies damage articular cartilage, but low dosages may be chondroprotective. The p urpose of this study was to evaluate how different concentrations of methyl prednisolone affect chondrocyte function and viability. Articular cartilage and chondrocytes were obtained from young adult horses, 1.5-3.5 years of a ge. Corticosteroid-induced changes in collagen expression were studied at t he transcriptional level by Northern blot analyses and at the translational level by measuring CM-proline incorporation into CHI-hydroxyproline. Fibro nectin mRNA splicing patterns were evaluated with ribonuclease protection a ssays. Cytotoxicity was studied using erythrosin B dye exclusion. Steady-st ate levels of type II procollagen mRNA decreased without concurrent changes in type I procollagen expression as the medium methylprednisolone concentr ations were increased from 1 x 10(1) to 1 X 10(8) pg/ml, dropping below 10% of control values by I x 101 pg/ml. Cytotoxicity occurred as methylprednis olone levels were increased further from 1 x 10(8) to 1 x 10(9) pg/ml. Chan ges in total collagen (protein) synthesis were less pronounced, but also de monstrated significant suppression between 1 x 10(4) and 1 x 10(8) pg/ml. C orticosteroid-induced changes in fibronectin isoform levels were evaluated in articular cartilage samples without in vitro culture. The cartilage-spec ific (V + C)(-) isoform was suppressed in both normal and inflamed joints b y a single intraarticular injection (0.1 mg/kg) of methylprednisolone. Comb ined, 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 co rticosteroid-induced cartilage degeneration. (C) 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.