Glucosamine Sulfate Reduces Prostaglandin E2 Production in Osteoarthritic Chondrocytes Through Inhibition of Microsomal PGE Synthase-1
+ Author Affiliations
- From the Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Notre-Dame Hospital, Montreal, Quebec, Canada.
- M. Kapoor, PhD, Assistant Research Professor, Department of Medicine, CRCHUM, Osteoarthritis Research Unit, Notre-Dame Hospital; F. Mineau, MSc, Research Assistant, CRCHUM, Osteoarthritis Research Unit, Notre-Dame Hospital; H. Fahmi, PhD, Associate Professor of Medicine, Department of Medicine, CRCHUM, Osteoarthritis Research Unit, Notre-Dame Hospital; J-P. Pelletier, MD, Professor of Medicine, Department of Pharmacology Accredited, University of Montreal, Head, Arthritis Division and Director, Osteoarthritis Research Unit, CRCHUM, Notre-Dame Hospital; J. Martel-Pelletier, PhD, Professor of Medicine, Department of Pharmacology Accredited, University of Montreal, Director, Osteoarthritis Research Unit, CRCHUM, Notre-Dame Hospital.
- Address correspondence to Dr. J. Martel-Pelletier, Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Notre-Dame Hospital, 1560 Sherbrooke Street East, Montreal, Quebec H2L 4M1, Canada. E-mail: firstname.lastname@example.org
Objective. Glucosamine sulfate (GS) has been inferred to have a potential antiinflammatory effect on osteoarthritis (OA). We investigated its effect on prostaglandin E2 (PGE2) in human OA chondrocytes, and the level in the PGE2 pathway at which its effect takes place.
Methods. We investigated the effect of GS treatment (0.05, 0.2, 1.0, and 2.0 mM) in OA chondrocytes in the absence or presence of interleukin 1ß (IL-1ß; 100 pg/ml). We determined the expression levels and protein production/activity of PGE2, cyclooxygenase-1 (COX-1), COX-2, microsomal PGE synthase-1 (mPGES-1), glutathione, and peroxisome proliferator-activated receptor-γ (PPARγ), using specific primers, antibodies, and assays.
Results. GS treatment at 1 and 2 mM significantly inhibited (p ≤ 0.03) production of endogenous and IL-1ß-induced PGE2. GS in both the absence and presence of IL-1ß did not significantly modulate COX-1 protein production, but GS at 1 and 2 mM demonstrated a decrease in COX-2 glycosylation in that it reduced the molecular mass of COX-2 synthesis. Under IL-1ß stimulation, GS significantly inhibited mPGES-1 messenger RNA expression and synthesis at 1 and 2 mM (p ≤ 0.02) as well as the activity of glutathione (p ≤ 0.05) at 2 mM. Finally, in both the absence and presence of IL-1ß, PPARγ was significantly induced by GS at 1 and 2 mM (p ≤ 0.03).
Conclusion. Our data document the potential mode of action of GS in reducing the catabolism of OA cartilage. GS inhibits PGE2 synthesis through reduction in the activity of COX-2 and the production and activity of mPGES-1. These findings may, in part, explain the mechanisms by which this drug exerts its positive effect on OA pathophysiology.
Towheed T, Maxwell L, Anastassiades TP, Shea B, Houpt J, Welch V, Hochberg MC, Wells GA
October 7, 2009
People with osteoarthritis who take glucosamine:
– may reduce their pain
– may improve their physical function
– will probably not have side effects
What is osteoarthritis and glucosamine?
Osteoarthritis (OA) is the most common form of arthritis that can affect the hands, hips, shoulders and knees. In OA, the cartilage that protects the ends of the bones breaks down and causes pain and swelling. Drug and non-drug treatments are used to relieve pain and/or swelling.
Glucosamine can be found naturally in the body and is used by the body as one of the building blocks of cartilage. Glucosamine can also be taken as a pill as a supplement to the diet, or sometimes as an injection. It can come in combination with other supplements (such as chondroitin), or by itself in the form of glucosamine hydrochloride or sulphate. The usual dose recommended on packages is 1500 mg per day or 500 mg three times a day.
In Europe, glucosamine is prescribed by health care providers. But in North America, people can buy glucosamine supplements without a prescription. This means that, in North America, glucosamine is not regulated and the pills may or may not truly contain the amount described on the label.
Best estimate of what happens after about 6 months
Pain: The high quality studies showed that pain improved about the same whether people took glucosamine or fake pills. If all of the studies are examined (including low quality and old studies), then glucosamine improved pain more than fake pills.
People who took fake pills had a pain score of 7 points on a 0 to 100 scale. Pain may improve by 10 more points with glucosamine than with fake pills.
Studies testing only the Rotta brand of glucosamine (including low quality and older studies) showed that glucosamine improved pain more than fake pills. People who took fake pills had a pain score of 6 points on a 0 to 20 scale. People who took the Rotta brand of glucosamine rated their pain 3 points lower than people who did not take glucosamine.
Function: The high quality studies show that glucosamine improved function more than fake pills when measured by one type of scale, but improved the same amount as fake pills when measured by another scale.
Studies testing only the Rotta brand of glucosamine (including low quality and older studies) showed that glucosamine improved function more than fake pills. People who took fake pills had a function score of 22 points on a 0 to 68 scale. People who took the Rotta brand of glucosamine had their ability to function improve by 2 points compared to people who did not take glucosamine.
There was no difference in the number of people who had side effects. Side effects mainly included stomach upset and other joint pain.
Crystalline glucosamine sulfate in the management of knee osteoarthritis: efficacy, safety, and pharmacokinetic properties
- Lucio C. Rovati
- Federica Girolami
- Stefano Persiani
Glucosamine is an amino monosaccharide and a natural constituent of glycosaminoglycans in articular cartilage. When administered exogenously, it is used for the treatment of osteoarthritis as a prescription drug or a dietary supplement. The latter use is mainly supported by its perception as a cartilage building block, but it actually exerts specific pharmacologic effects, mainly decreasing interleukin 1-induced gene expression by inhibiting the cytokine intracellular signaling cascade in general and nuclear factor-kappa B (NF-kB) activation in particular. As a whole, the use of glucosamine in the management of osteoarthritis is supported by the clinical trials performed with the original prescription product, that is, crystalline glucosamine sulfate. This is the stabilized form of glucosamine sulfate, while other formulations or different glucosamine salts (e.g. hydrochloride) have never been shown to be effective. In particular, long-term pivotal trials of crystalline glucosamine sulfate 1500 mg once daily have shown significant and clinically relevant improvement of pain and function limitation (symptom-modifying effect) in knee osteoarthritis. Continuous administration for up to 3 years resulted in significant reduction in the progression of joint structure changes compared with placebo as assessed by measuring radiologic joint space narrowing (structure-modifying effect). The two effects combined may suggest a disease-modifying effect that was postulated based on an observed decrease in the risk of undergoing total joint replacement in the follow up of patients receiving the product for at least 12 months in the pivotal trials. The safety of the drug was good in clinical trials and in the postmarketing surveillance. Crystalline glucosamine sulfate 1500 mg once daily is therefore recommended in the majority of clinical practice guidelines and was found to be cost effective in pharmacoeconomic analyses. Compared with other glucosamine formulations, salts, or dosage forms, the prescription product achieves higher plasma and synovial fluid concentrations that are above the threshold for a pharmacologically relevant effect, and may therefore justify its distinct therapeutic characteristics.