A well established model of arthritis induced in rabbit knee joints by immobilisation in full extension for 30 days was used to evaluate the in vivo effects of 2.5, 5.0, and 10.0 mg/kg body weight of tiaprofenic acid on articular cartilage proteoglycans. The drug was given subcutaneously every 24 hours during the entire immobilisation period. Immobilised animals not treated with drugs and normal animals were used as controls. In the non-drug treated immobilised animals articular cartilage showed evidence of surface damage accompanied by synovial hypertrophy and effusion. Proteoglycan concentrations were reduced in cartilages of these joints and the incorporation of 35SO2-4 into macromolecular proteoglycans was higher than in cartilages of non-immobilised controls. Gel filtration chromatographic studies of both resident and 35S labelled proteoglycans isolated from immobilised joint cartilage showed reduced aggregation and the presence of degraded proteoglycan subunit species. Whereas the administration of 10.0 mg/kg tiaprofenic acid every 24 hours to immobilised animals exacerbated the degradation and loss of proteoglycans from joint cartilages, 5.0 mg/kg tiaprofenic acid provided some protection of these macromolecules, as shown by the concentrations and extractability of proteoglycans from cartilages, which were comparable with those from non-immobilised controls. A high incorporation of 35S into proteoglycans was demonstrated, together with reduced catabolism of proteoglycans, indicating preservation of chondrocyte anabolic activity. At a tiaprofenic acid dose of 2.5 mg/kg, however, no beneficial effects on cartilage proteoglycans could be shown.
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