Glucosamine HCl reduces equine articular cartilage degradation in explant culture

Fenton, Jenifer I.; Chlebek-Brown, K. A.; Peters, Tonia L.; Caron, John P.; Orth, Michael

doi:10.1053/joca.1999.0299

Cited by 126 publications

(107 citation statements)

References 35 publications

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“…Higher concentrations (2.5 mg/ml or higher) of GLN alone inhibit MMP activity (Fenton et al 2000). Glucosamine also inhibits aggrecanases (enzymes involved in the initiation of proteoglycan degradation) in vitro (Sandy et al 1998).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of articular cartilage degradation by glucosamine‐HCl and chondroitin sulphate

Orth

Peters

Hawkins

2002

Equine Veterinary Journal

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SummaryGlucosamine and chondroitin sulphate in many animal and human trials has improved joint health. In vitro studies are beginning to clarify their mode of action. The objective of this research was to: 1) determine at what concentrations glucosamine-HCl (GLN) and/or chondroitin sulphate (CS) would inhibit the cytokine-induced catabolic response in equine articular cartilage explants and 2) to determine if a combination of the 2 was more effective at inhibiting the catabolic response than the individual compounds. Articular cartilage was obtained from carpal joints of horses (age 1-4 years). Cartilage discs (3.5 mm) were biopsied and cultured. Explants were incubated with lipopolysaccharide (LPS) in the presence of varying concentrations of GLN, CS, or both. Control treatments included explants with no LPS and LPS without GLN or CS. Media were analysed for nitric oxide (NO), prostaglandin E 2 (PGE 2 ) and keratan sulphate. Cartilage was extracted for analysis of metalloproteinases (MMP). Four experiments were conducted. In all experiments, GLN at concentrations as low as 1 mg/ml decreased NO production relative to LPS stimulated cartilage without GLN over the 4 day period. In general, CS at either 0.25 or 0.5 mg/ml did not inhibit NO production. The addition of CS to GLN containing media did not further inhibit NO production. GLN at concentrations as low as 0.5 mg/ml decreased PGE 2 production, whereas CS did not effect on PGE 2 . The combination of GLN/CS decreased MMP-9 gelatinolytic activity but had no effect on MMP-2 activity. The combination in 2 experiments tended to decrease MMP-13 protein concentrations and decreased keratan sulphate levels in media.Overall, the combination of GLN (1 mg/ml) and CS (0.25 mg/ml) inhibited the synthesis of several mediators of cartilage degradation. These results further support the effort to understand the role of GLN and CS in preserving articular cartilage in athletic horses.

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Section: Discussionmentioning

confidence: 99%

Inhibition of articular cartilage degradation by glucosamine‐HCl and chondroitin sulphate

Orth

Peters

Hawkins

2002

Equine Veterinary Journal

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“…12 Other in vitro studies show that incubation of chondral explants in glcN after exposure of the tissue to the proinflammatory cytokine interleukin-1 prevents the increase in PG release and MMP activity. 13 Thus, the hypotheses of the current study were that: during low intensity, intermittent cyclic loading, a high concentration of glcN-CS would upregulate the production of PGs to reduce the extent of matrix damage and cell death following an acute overload; and supplementation of the culture media would limit, or even mitigate, the degeneration effect noted to occur between 14 and 21 days in this model. These would suggest that athletes could take this nutraceutical prophylactically prior to and during intense practice and competition to protect their joint cartilage in case of excessive overload, such as during rupture of a ligament.…”

mentioning

confidence: 93%

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

Wei

Haut

2009

Journal Orthopaedic Research

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A recent study by our laboratory showed that 14 days of low intensity, intermittent cyclic preloading of chondral explants elevated the concentration of proteoglycans (PGs) to cause a mechanical stiffening of the explants prior to an acute overload and limit the extent of tissue damage. Longer term loading to 21 days resulted in tissue degradation prior to the acute traumatic event and excessive damage from an acute overload. Previous studies by others showed that bathing chondral explants in a supplement of glucosaminechondroitin sulfate (glcN-CS) upregulated the synthesis of tissue PGs, particularly in stressed tissue, and the supplement served as an antiinflammatory agent. Our current hypothesis was that the supplementation of culture media with a high concentration of glcN-CS would upregulate the production of tissue PG and limit or mitigate long-term degradation of chondral explants under cyclic preloading and limit tissue damage in an acute overload. We showed that, in the presence of supplement, cyclic preloading significantly increased tissue PG content and matrix modulus by about 65 and 300%, respectively, at 21 days, resulting in a reduction of matrix damage and cell death following an acute overload. These data show a biological action of high concentrations of this supplement and its effect on the mechanical properties in this in vitro model. In vitro studies of impact loading 1,2 on cartilage show cell death and matrix damage. In contrast, in vitro and in vivo studies showed positive aspects of low intensity, intermittent compressive loading, such as increased biosynthesis of proteoglycans (PGs). [3][4][5] Changes in PG and collagen contents of cartilage significantly alter the mechanical properties of this tissue. 6 Thus, it is reasonable to assume that cyclic preloading of cartilage can alter its mechanical properties and help determine the extent of matrix damage and cell death that will occur due to the blunt force overloading of a joint, such as during an acute knee ligament rupture. 7 Recent studies in our laboratory show that low intensity, intermittent cyclic preloading of chondral explants prior to an acute overload yields an increase in the synthesis of tissue PGs, resulting in a less severe traumatic insult for an acute overload. 8 Between 14 and 21 days of cyclic preloading, the explants experience a significant PG loss that leads to a dramatic loss in mechanical properties. Acute overloading of the explanted tissue then yields matrix damage and cell death significantly greater than nonpreloaded controls. A recent study by others shows a significant loss of tissue PG and cell death with production of matrix metalloproteinase (MMP-3) adjacent to damaged collagen fibers under cyclic compression at 0.5 Hz for intensities of 1 and 5 MPa over 24 h. 9 Similarly, under 0.5 MPa of 1 Hz cyclic loading, a significant increase in the MMP-2 and -9 synthesis was found after 3 h. 10 The combination of glucosamine-chondroitin sulfate (glcN-CS) was shown in in vitro studies to function as a ''...

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“…Several clinical trials have shown the significant symptom-modifying effect of glucosamine in OA (18)(19)(20). In this context, biochemical and pharmacological studies have suggested in vitro that glucosamine possibly exhibit chondroprotective action by inhibiting the degradation and stimulating the synthesis of proteoglycans (21,22).…”

Section: Discussionmentioning

confidence: 99%

“…Several short-and long-term clinical trials in osteoarthritis have shown the significant symptom-relieving and structure-modifying effects of glucosamine (18)(19)(20). Importantly, it has been revealed in vitro that glucosamine can inhibit the degradation and stimulate the synthesis of glycosaminoglycans (proteoglycans), thereby possibly exhibiting chondroprotective action (21,22). Moreover, glucosamine has been shown to inhibit the expression of collagen-degrading enzymes (matrix metalloproteinases, MMPs) but augment the expression of type II collagen in chondrocytes in vitro (23,24).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the effect of glucosamine administration on biomarkers for cartilage and bone metabolism in soccer players

Yoshimura

Sakamoto²,

Tsuruta³

et al. 2009

Int J Mol Med

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Abstract. In the present study, to investigate the effect of glucosamine, a component of glycosaminoglycans with a chondroprotective action, on articular cartilage in athletes, we looked at soccer players, who expose their joints to excessive motion and loading, and compared the levels of biomarkers for type II collagen degradation (CTX-II) and type II collagen synthesis (CPII) between soccer players and non-athlete controls, and in soccer players before and after glucosamine-administration. CTX-II (P<0.01) and CPII (P=0.08) levels were substantially elevated in soccer players compared with those in controls, indicating that cartilage metabolism (type II collagen degradation and synthesis) is increased in soccer players. Of note, glucosamine administration (1.5 g and 3 g/day for 3 months) significantly decreased the CTX-II level (P<0.05); however, the effect disappeared after withdrawal of administration. In contrast, glucosamine administration did not essentially affect the increased level of CPII. Furthermore, cartilage damage was evaluated by using the ratio of type II collagen breakdown to synthesis (CTX-II/CPII). The ratio in soccer players was significantly higher than that in controls (P<0.05), suggesting that type II collagen degradation is relatively enhanced compared with type II collagen synthesis in soccer players than in control students. Of importance, the ratio was reduced by glucosamine administration but returned to the pre-administration level after withdrawal of administration. Together these observations suggest that glucosamine is expected to exert a chondroprotective action in athletes (soccer players) by preventing type II collagen degradation but maintaining type II collagen synthesis, although the effect is transient and disappears after withdrawal of administration.

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Glucosamine HCl reduces equine articular cartilage degradation in explant culture

Cited by 126 publications

References 35 publications

Inhibition of articular cartilage degradation by glucosamine‐HCl and chondroitin sulphate

Inhibition of articular cartilage degradation by glucosamine‐HCl and chondroitin sulphate

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

Evaluation of the effect of glucosamine administration on biomarkers for cartilage and bone metabolism in soccer players

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