Glucosamine and chondroitin sulfate: biological response modifiers of chondrocytes under simulated conditions of joint stress

Objective: To test the hypothesis that chondrocytes are more responsive to the chondroprotective agents, glucosamine (glcN) and chondroitin sulfate (CS), under in vitro conditions simulating in vivo joint stress. Design: Synthetic and anticatabolic activities of bovine articular cartilage were assayed using 35-sulfate labeling and assaying the specific activity of glycosaminoglycans (GAGs) under the conditions of enzyme-induced matrix depletion, heat stress, mechanical compression and cytokine stress. Results: The response of cartilage to simulated conditions of in vivo stress varies, depending on the type stress and age of the animal. Cartilage from aged animals was more responsive to stress and to glcN and CS. Pronase-induced matrix depletion and mechanical stress increased proteoglycan synthetic activity. Exposure to glcN and CS significantly enhanced this stress response from 85 to 191% and from 40 to 1000%, respectively. Heat stress and stromelysin digestion decreased synthetic activity, which was reversed or normalized on exposure to glcN and CS. Cartilage from young joints was somewhat refractory to the level of stress imposed and to treatment with glcN and CS. Conclusion: The metabolic response of cartilage from aged animals to glcN and CS under simulated conditions of in vivo stress is significantly greater than that seen in nonstressed or young tissue. By enhancing the 'protective' metabolic response of chondrocytes to stress, glcN and CS may improve its ability for repair and regeneration. These observations suggest that these compounds function as biological response modifiers (BRMs), agents which boost natural protective responses of tissues under adverse environmental conditions. (C) 2003 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.