Efficacy of JOINS on Cartilage Protection in Knee Osteoarthritis: Prospective Randomized Controlled Trial

PURPOSE: In this study, we compared the clinical efficacy of JOINS (SKI306X, SK Chemicals) with placebo on cartilage protection using magnetic resonance imaging (MRI). MATERIALS AND METHODS: Sixty-nine patients were randomized to the JOINS group (200 mg, three times daily for 1 year; n=33) or the placebo group (n=36). Changes in cartilage volume and thickness were measured using MRI. Changes in the delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) index, subchondral bone marrow abnormality scores, and clinical scores including knee pain visual analog scale (VAS) score and Korean Western Ontario and McMaster Universities Osteoarthritis Index (K-WOMAC) were also evaluated. RESULTS: Changes in cartilage thickness and volume and subarticular bone marrow abnormality scores were not different between groups. Changes in the dGEMRIC index in the lateral tibial plateau were greater in the JOINS group than in the placebo group (19.64±114.33 msec vs. −57.77±123.30 msec; p=0.011). Significantly greater changes in VAS were observed in the JOINS group than in the placebo group (−26.00±12.25 vs. −12.47±21.54; p=0.002) and K-WOMAC (−15.42 ± 7.73 vs. −8.15±13.71; p=0.003). CONCLUSIONS: Compared with placebo, JOINS had superior clinical efficacy in regard to cartilage protection.

SKI306X inhibition of glycosaminoglycan degradation in human cartilage involves down-regulation of cytokine-induced catabolic genes

BACKGROUND/AIMS: SKI306X, a mixed extract of three herbs, Clematis mandshurica (CM), Prunella vulgaris (PV), and Trichosanthes kirilowii (TK), is chondroprotective in animal models of osteoarthritis (OA). The objectives of this study were to investigate its effect on interleukin (IL)-1beta-induced degradation of glycosaminoglycan (GAG) and the basis of its action in human OA cartilage, as well as to screen for the presence of inhibitors of matrix metalloproteinase (MMP)-13 and a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-4 in SKI306X and its component herbs, as well as in fractions from SKI306X. METHODS: Human OA chondrocytes and cartilage explants were obtained during total knee replacements and incubated with IL-1beta +/- oncostatin M with or without SKI306X or its component herb extracts. GAG degradation was assayed in cartilage explants using a commercial kit. Expression of genes involved in cartilage destruction was measured by real-time polymerase chain reaction using chondrocyte RNA. SKI306X was fractionated by preparative liquid chromatography to test for the presence of inhibitors of MMP-13 and ADAMTS-4. RESULTS: SKI306X and PV inhibited IL-1beta-induced GAG release from cartilage explants, and SKI306X, CM, PV, and TK inhibited IL-1beta-induced MMP gene expression. Unexpectedly, SKI306X greatly stimulated IL-1beta + oncostatin M-induced ADAMTS-4 gene expression, probably due to its TK component. Some fractions of SKI306X also inhibited ADAMTS-4 activity. CONCLUSIONS: SKI306X and its herbal components inhibit GAG degradation and catabolic gene expression in human OA chondrocytes and cartilage explants. SKI306X likely also contains one or more ADAMTS-4 inhibitor.