Corticosteroids alter the differentiated phenotype of articular chondrocytes

Susan L. Fubini, Rory J. Todhunter, Nancy Burton-Wurster, Margaret Vernier-Singer, James N. MacLeod

Research output: Contribution to journalArticlepeer-review

67 Scopus citations


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 × 101 to 1 × 108 pg/ml, dropping below 10% of control values by 1 × 105 pg/ml. Cytotoxicity occurred as methylprednisolone levels were increased further from 1 × 108 to 1 × 109 pg/ml. Changes in total collagen (protein) synthesis were less pronounced, but also demonstrated significant suppression between 1 × 104 and 1 × 108 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.

Original languageEnglish
Pages (from-to)688-695
Number of pages8
JournalJournal of Orthopaedic Research
Issue number4
StatePublished - 2001

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grant AR44340, the Arthritis Foundation, and the Grayson–Jockey Club Research Foundation, Inc.

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine


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