Oral glucosamine increases expression of transforming growth factor beta 1 (TGF beta 1) and connective tissue growth factor (CTGF) mRNA in rat cartilage and kidney: Implications for human efficacy and toxicity

[摘要]：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 mu M, spanning the human exposure range. Relative expression of both TGF beta 1 and CTGF mRNA were significantly increased up to 2.3-fold in liver, kidney and articular cartilage when evaluated 4 h after final dose. Apparent threshold serum glucosamine (C) concentration required to increase TGF beta 1 expression in cartilage was 10-20 mu M. These increases were associated with significant increases in UDP-N-acetylglucosamine concentrations suggesting increased hexosamine flux. Both TGF beta 1 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 TGF beta 1 and CTGF expression in vivo and provides a mechanistic rationale for reported beneficial effects of glucosamine therapy. Induction of renal TGF beta 1 and CTGF mRNA suggests that potential sclerotic side-effects may occur following consumption of potent glucosamine preparations. Published by Elsevier Inc.

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