Effects of Interleukin-1 and Anti-Inflammatory Drugs on the Degradation of Human Articular Cartilage

Abstract

It has been suggested that metalloproteases produced by chondrocytes play an important role in cartilage breakdown in joint diseases. The aim of this study was to investigate changes in enzyme activities in human rheumatoid and osteoarthritic articular cartilage. Cartilage fragments were incubated with various drugs for 48 hours. The concentrated culture media were used as enzyme solutions. Collagenase was assayed using FITC-collagen as the substrate. Proteoglycanase (PGase) was measured either by the release of ³⁵Slabelled proteoglycans from cartilage into the medium, or by enzyme assay using proteoglycan monomer bound to fluorescein-conjugated hyaluronic acid as the substrate. Collagenase and proteoglycanase were found only in trace amounts in the concentrated media of healthy cartilage. Interleukin-1 (IL-1) enhanced the enzyme activities significantly. Marked increases of enzyme activities were observed in the concentrated media of rheumatoid (RA) and osteoarthritic (OA) cartilage. The sensitivity to interleukin-1 was also higher in OA and RA cartilage compared with healthy cartilage. Dexamethasone (10⁶ mol/L) markedly depressed enzyme activity. Tiaprofenic acid (4 × 10⁻⁵ mol/L) also decreased enzyme activity, whereas indomethacin (4 × 10⁻⁶ mol/L) and naproxen (3 × 10⁻⁴ mol/L) had no effect.