Effects of diclofenac, aceclofenac and meloxicam on the metabolism of proteoglycans and hyaluronan in osteoarthritic human cartilage

1 Since nonsteroidal anti-inflammatory drugs (NSAIDs) may impair the abilit y of the chondrocyte to repair its damaged extracellular matrix, we explore d the changes in the metabolism of newly synthesized proteoglycan and hyalu ronan (HA) molecules produced by aceclofenac, diclofenac and meloxicam in h uman osteoarthritic (OA) cartilage. 2 Explants were sampled from the medial femoral condyle and were classified by use of the Mankin's histological-histochemical grading system. Cartilag e specimens exhibited moderate (M) OA in 20 subjects and had severe (S) OA in 20. 3 Cartilage explants were pulsed with [-3H]-glucosamine and chased in the a bsence or in the presence of 0.3-3 mug ml(-1) of either aceclofenac, diclof enac or meloxicam. After papain digestion. the labelled chondroitin sulphat e ([-3H]-proteoglycans) and [-3H]-HA molecules present in the tissue and me dia were purified by anion-exchange chromatography. 4 In cartilage with MOA and SOA, the metabolic balance of proteoglycan and HA was unaffected by diclofenac. In contrast, and in a dose-dependent manne r. aceclofenac and meloxicam both increased the synthesis of proteoglycans and HA in explants with MOA and SOA; these two NSAIDs also reduced signific antly the net loss of [-3H]-proteoglycans and [-3H]-HA molecules from carti lage explants. 5 The data obtained in short-term in vitro cultures indicate that, at the c oncentrations found in synovial fluid, aceclofenac and meloxicam may exert a favourable effect on the overall metabolism of proteoglycans and HA in ca rtilage with MOA and SOA.