Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants

Objective: To investigate the effect of glucosamine (GIcN) in a human osteoarthritic explant model on expression of genes involved in anabolic and catabolic activities of chondrocytes. Methods: Human osteoarthritic explants, obtained during knee arthroplasty surgery, were pre-cultured (3 days) and treated with glucosamine-hydrochloride (GlcN-HCl) or glucosamine-3-sulphate (GlcN-S) at 0.5 mM and 5 mM (4 days). RNA was isolated from the explants and real time RT-PCR was performed. Additionally, total matrix metalloproteinase (MMP) activity was measured in culture medium. Results: Addition of 5 mM GlcN led to significant down-regulation of aggrecan (2.65-7.73-fold) and collagen type 11 (7.75-22.17-fold) gene expression, indicating inhibited anabolic activity. Considering catabolic activities, 5 mM GIcN significantly down-regulated aggrecanase-1 and MMP3 and 5 mM GlcN-S additionally down-regulated aggrecanase-2 and tissue inhibitor of MMP gene expression significantly. Gene expression was not significantly altered by 0.5 mM GlcN. Total MMP activity in culture medium was only significantly reduced after addition of 5 mM GlcN-HCl. Conclusion: The effects of GlcN on gene expression in a human osteoarthritic explant model suggest that enzymatic breakdown of the extracellular matrix might be reduced by the addition of 5 mM GlcN. Additionally, restoration of already damaged cartilage is not to be expected, because gene expression of anabolic genes is also down-regulated. We suggest that chondroprotective properties of GlcN in vivo may be based on inhibiting further degradation due to catabolic activities, rather than on the ability to rebuild cartilage. (c) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.