The use of intra-articular corticosteroid injections for their anti-inflammatory effects is widespread amongst clinicians. Despite their use in both rheumatoid arthritis and osteoarthritis, the effect of these agents on articular chondrocytes is not fully established. Previous reports suggest a detrimental effect on cartilage explants resulting from inhibition of matrix synthesis1. However it has also been suggested that the beneficial effects in vivo may be due to prevention of inflamed synovium causing cartilage degradation2. Our aim was to assess the effect of a commercially available preparation of methylprednisolone (MP), at clinical doses, on articular chondrocytes cultured in vitro.
Bovine articular chondrocytes were isolated by sequential digestion with pronase and collagenase and seeded in 2% alginate at 1x107 cells/ml. The constructs were cultured for up to 15 days in standard culture medium (DMEM + 20% Fetal calf serum) containing varying concentrations of MP, including doses equivalent to those found in vivo. The medium was replaced every 3 days and representative constructs were removed from culture, digested and assayed for DNA and glycosaminoglycans. Further constructs were fixed in 4% paraformaldehyde for standard histology and immunolocalisation of collagen types I, II and chondroitin-6-sulphate.
Chondrocytes cultured in MP containing medium showed a significant abnormality in cell morphology compared to controls at the day 15 time point. Histologically there was evidence of cell necrosis, reduced amounts of extracellular matrix and loss of collagen type II staining. The effects were dose dependant, with significant damage occurring even at clinical doses. Biochemical analysis revealed a reduction in DNA content and an inhibition of glycosaminoglycan and collagen type II synthesis. In contrast, in the controls, there was cell proliferation with a cell doubling time of 14 days, collagen type II containing extracellular matrix synthesis occurred and the chondrocytes maintained their phenotype throughout the culture period.
Methylprednisolone has a significant detrimental effect on cultured articular chondrocytes in vitro. There was significant cell necrosis associated with inhibition of extracellular matrix synthesis. Based on these results, intra-articular corticosteroid injections should be used with extreme caution.