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Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants
E J Uitterlinden1, H Jahr, J L M Koevoet
1Erasmus MC, University Medical Center Rotterdam, Department of Orthopaedics, The Netherlands.
Objective:
To investigate the effect of glucosamine (GlcN) 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 0.5mM and 5mM (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 5mM GlcN led to significant down-regulation of aggrecan (2.65-7.73-fold) and collagen type II (7.75-22.17-fold) gene expression, indicating inhibited anabolic activity. Considering catabolic activities, 5mM GlcN significantly down-regulated aggrecanase-1 and MMP3 and 5mM GlcN-S additionally down-regulated aggrecanase-2 and tissue inhibitor of MMP gene expression significantly. Gene expression was not significantly altered by 0.5mM GlcN. Total MMP activity in culture medium was only significantly reduced after addition of 5mM GlcN-HCl.
Conclusion:
The effects of GlcN on gene expression in a human osteoarthritic explant model suggest that enzymatic breakdown of the extra-cellular matrix might be reduced by the addition of 5mM 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.
