Maintenance of the synthesis of large proteoglycans in anatomically intact murine articular cartilage by steroids and insulin-like growth factor I.

Abstract

The exact regulation of the synthesis of cartilage specific molecules, such as collagen type II and aggrecan, by articular chondrocytes is unknown, but growth factors and hormones probably play an important part. The effects of glucocorticosteroids (prednisolone and triamcinolone), in combination with insulin-like growth factor I (IGF-I), on the synthesis and hydrodynamic volume of proteoglycans from murine patellar cartilage were investigated. The in vitro effect of IGF-I and steroids on proteoglycan synthesis in murine patellar cartilage was evaluated by [35S]sulphate incorporation in combination with dissociative gel chromatography using a Sephacryl S-1000 column. The impact of in vivo prednisolone (0-5 mg/kg) on proteoglycan synthesis in murine patellar cartilage was analysed by [35S]sulphate incorporation immediately after dissection from the knee joint. Prednisolone stimulated proteoglycan synthesis in murine patellar cartilage from normal knees and in cartilage from knees injected with papain in vitro in the absence and presence of IGF-I. Moreover, oral administration of prednisolone for seven days to C57Bl10 mice resulted in enhanced proteoglycan synthesis in patellar cartilage. The incubation of patellar cartilage for 48 hours without serum or growth factors led to the synthesis of proteoglycans with a smaller hydrodynamic volume than those synthesised immediately after dissection of the patellae. This could either be circumvented by the addition of IGF-I or by the addition of glucocorticosteroids (prednisolone or triamcinolone) to the culture medium. These results show that in a dose range of 0.0003-0.3 mmol/l, glucocorticosteroids, like IGF-I, stimulate proteoglycan synthesis and maintain the synthesis of hydrodynamically large proteoglycans by chondrocytes from murine articular cartilage. This indicates that glucocorticosteroids might play a part in the preservation of matrix integrity in articular cartilage.