Effects of glucosamine derivatives and uronic acids on the production of glycosaminoglycans by human synovial cells and chondrocytes

Glucosamine (GlcN) has been widely used to treat osteoarthritis (OA) in humans. However, its chondroprotective action on the joint is poorly understood. In this study, to elucidate the chondroprotective action of GlcN, we examined the effects of GlcN-derivatives (GlcN and N-acetyl-D-glucosamine) and uronic acids (D-glucuronic acid and D-galacturonic acid) (0.1-1 mM) on the production of glycosaminoglycans (GAG), such as hyaluronic acid (HA), keratan sulfate and sulfated GAG by human synovial cells and chondrocytes. The results indicate that among GlcN-derivatives and uronic acids, GlcN but not N-acetyl-D-glucosamine, D-glucuronic acid and D-galacturonic acid induce the production of HA by synovial cells and chondrocytes at >0.25 and >0.1 mM (p<0.05), respectively, and the production levels are much higher (>10-fold) in synovial cells compared to chondrocytes. In contrast, neither N-acetyl-D-glucosamine, D-glucuronic acid nor D-galacturonic acid affected the production of keratan sulfate and sulfated GAG by these cells. Moreover, the experiments with 3H-labeled GlcN indicated that GlcN can be incorporated and utilized for the production of GAG (including HA) by synovial cells and chondrocytes. In addition, GlcN (1 mM) up-regulates the expression of HA-synthesizing enzymes (hyaluronan synthases) in synovial cells and chondrocytes. Together these observations indicate that GlcN may exhibit chondroprotective action on joint diseases such as OA by modulating the expression of HA-synthesizing enzymes and inducing the production of HA (a major component of GAG contained in synovial fluid) especially by synovial cells.