Abstract
Glucosamine (2-amino-2-deoxyglucose, GlcN), a naturally occurring amino monosaccharide, has been widely used to treat osteoarthritis (OA) in humans. However, the effects of GlcN on autophagy in chondrocyte are still unknown. In this study, to elucidate the chondroprotective action of GlcN via autophagy, we evaluated the effect of GlcN on the expression of autophagy-related molecules (LC3-II, Beclin-1, ATG5 and ATG7) using a human chondrocyte cell line Hs 819.T. GlcN significantly increased protein level of LC3-II and mRNA expression of Beclin-1, ATG5 and ATG7. Moreover, GlcN significantly increased the protein level of SIRT1. Importantly, the GlcN-induced increase of LC3-II protein was inhibited by EX527 (a SIRT1 inhibitor). Moreover, GlcN did not effect the S6K phosphorylation, as a target of mammalian target of rapamycin (mTOR). In addition, GlcN significantly decreased the acetylation (activation) of p53, which negatively regulates autophagy independent of mTOR.
Together these observations suggest that GlcN increases the expression of SIRT1 and possibly induces autophagy through the suppression of p53 activity in chondrocytes independent of mTOR, thereby exhibiting the chondroprotective action.
