2014 Volume 60 Issue 6 Pages 580-587
Glucosamine, a naturally occurring amino monosaccharide, is present in the connective and cartilage tissues as a component of glycosaminoglycans. Thus, glucosamine has been widely used to treat osteoarthritis, a joint disease characterized by cartilage degeneration, in humans. We previously revealed that glucosamine induces the production of hyaluronic acid by synovial cells and chondrocytes, and increases the expression of hyaluronic acid-synthesizing enzymes (HAS) in these cells, indicating that it exhibits chondroprotective action on osteoarthritis by modulating the expression of HAS and inducing the production of hyaluronic acid (a major component of glycosaminoglycans) by synovial cells and chondrocytes. Furthermore, we recently examined the expression of the sirtuin (SIRT) gene family in chondrocytes, and revealed that glucosamine significantly increased the mRNA and protein levels of SIRT1 (a putative gene involved in lifespan elongation) in chondrocytes, suggesting that glucosamine can upregulate the mRNA and protein levels of SIRT1 in chondrocytes, thereby possibly exhibiting protective action against osteoarthritis.
In addition, glucosamine is expected to exert anti-inflammatory action since it downregulates the expression of pro-inflammatory cytokines. We recently identified a transcription factor, Sp1, as an O-linked-N-acetylglucosamine (O-GlcNAc) -modified protein. Namely, glucosamine enhanced the O-GlcNAc modification of Sp1, and the effect was abolished by alloxan, an O-GlcNAc transferase inhibitor. Moreover, glucosamine downregulated the expression of IL-8, and the effect was abrogated by alloxan. These observations apparently suggest that glucosamine modulates (suppresses) IL-8 expression via the O-GlcNAc modification of Sp1 in synovial cells.
Together, these observations indicate that glucosamine can be therapeutically utilized as a functional molecule with chondroprotective and anti-inflammatory actions in the body.