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Arch Biochem Biophys. 2011 Jun 1;510(1):11-8. doi: 10.1016/j.abb.2011.03.014. Epub 2011 Apr 3.

Oral glucosamine increases expression of transforming growth factor β1 (TGFβ1) and connective tissue growth factor (CTGF) mRNA in rat cartilage and kidney: implications for human efficacy and toxicity.

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  • 1Office of Scientific Coordination, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.

Abstract

Glucosamine is used for alleviating pain in osteoarthritis. Clinical trials have reported that glucosamine has equivocal efficacy. Glucosamine is also used in cell cultures to stimulate hexosamine flux and protein O-glycosylation, but at many-fold greater concentrations than those in human plasma following oral dosing. Lean Zucker rats were dosed orally for 6 weeks with glucosamine hydrochloride at doses (0-600 mg/kg/day) that produced peak serum concentrations of <1-35 μM, spanning the human exposure range. Relative expression of both TGFβ1 and CTGF mRNA were significantly increased up to 2.3-fold in liver, kidney and articular cartilage when evaluated 4h after final dose. Apparent threshold serum glucosamine (C(max)) concentration required to increase TGFβ1 expression in cartilage was 10-20 μM. These increases were associated with significant increases in UDP-N-acetylglucosamine concentrations suggesting increased hexosamine flux. Both TGFβ1 and CTGF are mediators of chondrocyte proliferation and cartilage repair. Study demonstrates that oral glucosamine doses that produce clinically relevant serum glucosamine concentrations can induce tissue TGFβ1 and CTGF expression in vivo and provides a mechanistic rationale for reported beneficial effects of glucosamine therapy. Induction of renal TGFβ1 and CTGF mRNA suggests that potential sclerotic side-effects may occur following consumption of potent glucosamine preparations.

Published by Elsevier Inc.

PMID:
21466783
[PubMed - indexed for MEDLINE]
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