N-Acetylglucosamine Prevents IL-1β-Mediated Activation of Human Chondrocytes

Abstract

Glucosamine represents one of the most commonly used drugs to treat osteoarthritis. However, mechanisms of its antiarthritic activities are still poorly understood. The present study identifies a novel mechanism of glucosamine-mediated anti-inflammatory activity. It is shown that both glucosamine and N-acetylglucosamine inhibit IL-1β- and TNF-α-induced NO production in normal human articular chondrocytes. The effect of the sugars on NO production is specific, since several other monosaccharides, including glucose, glucuronic acid, and N-acetylmannosamine, do not express this activity. Furthermore, N-acetylglucosamine polymers, including the dimer and the trimer, also do not affect NO production. The observed suppression of IL-1β-induced NO production is associated with inhibition of inducible NO synthase mRNA and protein expression. In addition, N-acetylglucosamine also suppresses the production of IL-1β-induced cyclooxygenase-2 and IL-6. The constitutively expressed cyclooxygenase-1, however, was not affected by the sugar. N-acetylglucosamine-mediated inhibition of the IL-1β response of human chondrocytes was not associated with the decreased inhibition of the mitogen-activated protein kinases c-Jun N-terminal kinase, extracellular signal-related kinase, and p38, nor with activation of the transcription factor NF-κB. In conclusion, these results demonstrate that N-acetylglucosamine expresses a unique range of activities and identifies a novel mechanism for the inhibition of inflammatory processes.

Integrated regulatory responses of fimB to N -acetylneuraminic (sialic) acid and GlcNAc in Escherichia coli K-12

“…Thus, the factors that regulate the offto-on phase variation of fim could each signal activation of host defenses to the bacterium, to suppress expression of the adhesin, and, hence, help limit inflammation. GlcNAc is an antiinflammatory, mediating effects on both nitric oxide and IL-6 production, and shows promise in the treatment of Crohn's disease (60,61). Inhibition of the expression of bacterial factors such as type 1 fimbriation could contribute to the efficacy of this and other amino sugars as antiinflammatory agents.…”

Cytokine Regulation of Facilitated Glucose Transport in Human Articular Chondrocytes

“…Glucose serves as a main energy source in chondrocytes (4,5), as a main precursor for glycosaminoglycan synthesis (6, 7), and as a regulator of the cell responses to certain growth factors (44). GLUTs also participate in facilitated transport of glucosamine and N-acetylglucosamine (45,46), which can modify inflammatory responses of chondrocytes (47) and serve as efficient precursors of glycosaminoglycan synthesis (48). Finally, GLUTs (predominantly GLUT1 and GLUT3) facilitate transport of dehydroascorbic acid (49), which induces chondrocyte differentiation (50) and regulates extracellular matrix gene expression, including type II collagen (51).…”

Multiple Signals Induce Endoplasmic Reticulum Stress in Both Primary and Immortalized Chondrocytes Resulting in Loss of Differentiation, Impaired Cell Growth, and Apoptosis

“…Cartilage aging and age-associated cartilage diseases such as osteoarthritis are associated with increased apoptosis (51). In addition, abnormal glucose metabolism has been implicated in the pathogenesis of osteoarthritis (52,53). Therefore, it is reasonable to predict that abnormal matrix synthesis, and chondrocyte apoptosis during cartilage aging and diseases might be linked to ER stress.…”