INTRODUCTION: Commonly used as an oral supplement, chondroitin has demonstrated significant anti‐inflammatory effects in animal models and has been shown to inhibit inflammatory and catabolic mediators in cartilage. However, the effects of chondroitin on intervertebral disc cell signaling have not been explored.
METHODS: Annulus fibrosus cells were isolated from New Zealand White rabbits and were exposed to chondroitin‐6‐sulfate (CS) at 1 or 100 ug/mL thirty minutes prior to inflammatory (1ng/mL IL‐1 beta) or mechanical stimulation using the FX‐4000™ Tension system (6% stress at 0.1 Hz) for 24 hours. Relative gene expression of inflammatory markers was analyzed through RT‐PCR of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX‐2). The concentration of Prostaglandin E2 (PGE2) was measured in the media by commercially available ELISA kit (R&D Systems).
RESULTS: Under conditions of inflammatory stimulation, CS at low concentration resulted in decreased expression of iNOS and COX‐2, but increased expression at high concentration. However, PGE2 concentrations were decreased after exposure to either concentration. Similar to inflammatory stimuli alone, under conditions of combined mechanical and inflammatory stimuli, low dose CS significantly decreased iNOS and COX‐2 gene expression, while high dose CS increased expression. Again, PGE2 concentrations were decreased after exposure to either concentration after stimulation with both inflammatory and mechanical stimuli.
DISCUSSION: Data indicated that Chondroitin‐6‐Sulfate supplementation was more beneficial at lower concentrations than higher concentrations under inflammatory conditions, and this effect was more significant under conditions of mechanical stimulation. These data suggest that chondroitin‐6‐sulfate may blunt the catabolic effects of both inflammatory and mechanical stimuli in the intervertebral disc, and suggest a biologic plausibility for a potential mechanism of action.