Glucosamine (GlcN) has been widely used to treat osteoarthritis (OA) in humans. However, the effects of GlcN on genes related to cartilage metabolism are still unknown. In the present study, to elucidate the chondroprotective action of GlcN on OA, we examined the effects of GlcN (0.1-10 mM) on the expression of the sirtuin (SIRT) genes as well as type II collagen and matrix metalloproteinases (MMPs) using a human chondrocyte cell line SW 1353. SW 1353 cells were incubated in the absence or presence of GlcN. RT-PCR analyses revealed that GlcN markedly increased the mRNA expression of type II collagen (COL2A1). By contrast, the levels of MMP-1 and MMP-9 mRNA were only slightly increased by GlcN. Furthermore, western blot analyses revealed that GlcN significantly increased the protein level of COL2A1. Importantly, GlcN enhanced the mRNA expression and protein level of SIRT1, an upstream-regulating gene of COL2A1. Moreover, a SIRT1 inhibitor suppressed GlcN-induced COL2A1 gene expression. Together these observations suggest that GlcN enhances the mRNA expression and protein level of SIRT1 and its downstream gene COL2A1 in chondrocytes, thereby possibly exhibiting chondroprotective action on OA.