Glucosamine prevents in vitro collagen degradation in chondrocytes by inhibiting advanced lipoxidation reactions and protein oxidation

Abstract

Osteoarthritis (OA) affects a large segment of the aging population and is a major cause of pain and disability. At present, there is no specific treatment available to prevent or retard the cartilage destruction that occurs in OA. Recently, glucosamine sulfate has received attention as a putative agent that may retard cartilage degradation in OA. The precise mechanism of action of glucosamine is not known. We investigated the effect of glucosamine in an in vitro model of cartilage collagen degradation in which collagen degradation induced by activated chondrocytes is mediated by lipid peroxidation reaction. Lipid peroxidation in chondrocytes was measured by conjugated diene formation. Protein oxidation and aldehydic adduct formation were studied by immunoblot assays. Antioxidant effect of glucosamine was also tested on malondialdehyde (thiobarbituric acid-reactive substances [TBARS]) formation on purified lipoprotein oxidation for comparison.Glucosamine sulfate and glucosamine hydrochloride in millimolar (0.1 to 50) concentrations specifically and significantly inhibited collagen degradation induced by calcium ionophore-activated chondrocytes. Glucosamine hydrochloride did not inhibit lipid peroxidation reaction in either activated chondrocytes or in copper-induced oxidation of purified lipoproteins as measured by conjugated diene formation. Glucosamine hydrochloride, in a dosedependent manner, inhibited malondialdehyde (TBARS) formation by oxidized lipoproteins. Moreover, we show that glucosamine hydrochloride prevents lipoprotein protein oxidation and inhibits malondialdehyde adduct formation in chondrocyte cell matrix, suggesting that it inhibits advanced lipoxidation reactions. Together, the data suggest that the mechanism of decreasing collagen degradation in this in vitro model system by glucosamine may be mediated by the inhibition of advanced lipoxidation reaction, preventing the oxidation and loss of collagen matrix from labeled chondrocyte matrix. Further studies are needed to relate these in vitro findings to the retardation of cartilage degradation reported in OA trials investigating glucosamine.

Biochemical Parameters in Toxicological Studies in Africa

“…Clinically, an increased level of MDA is observed in the corneas of patients suffering from keratoconus and bulloskeratopathy. It also can be found in tissue sections of joints from patients with osteoarthritis [123,124].…”

High levels of glucosamine–chondroitin sulfate can alter the cyclic preload and acute overload responses of chondral explants

“…The effect, however small, may be due to an increase in collagen production by chondrocytes in the supplemented groups. 22 Tiku et al 23 showed that treatment of chondrocytes with a similar concentration of glucosamine prevents in vitro collagen degradation over time. More likely, the higher collagen content may reflect the fact that the supplemented group was stiffened because of a rise in PG content and yielded less matrix damage.…”

Scientific Opinion on the substantiation of a health claim related to glucosamine hydrochloride and reduced rate of cartilage degeneration and reduced risk of development of osteoarthritis pursuant to Article 14 of Regulation (EC) No 1924/2006

“…One in vitro study reported the effect of glucosamine hydrochloride and glucosamine sulphate on collagen degradation induced by calcium ionophore-activated chondrocytes (Tiku et al, 2007). The Panel considers that the evidence provided does not establish that an effect of glucosamine on the degeneration of collagen in this in vitro model can predict an effect on cartilage degeneration in humans.…”