EFFECTS OF LOW DOSE GLUCOSAMINE ON EQUINE ARTICULAR CELLS

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: HATCH
• Reporting Frequency: Annual
• Accession No.: 0205508
• Project Start Date: Oct 1, 2005
• Project End Date: Sep 30, 2006
• Program Code: [(N/A)]- (N/A)

Recipient Organization
UNIVERSITY OF ILLINOIS
2001 S. Lincoln Ave.
URBANA,IL 61801

Performing Department
VETERINARY RES AND EXTENSION

Non Technical Summary
Glucosamine has shown promise as a treatment for equine osteoarthritis, however most of the existing research has been performed with concentrations in excess of those achieved clinically. This study will investigate the effects of glucosamine on cells from both cartilage and synovium to determine how clinically achievable concentrations affect these joint cells. This study will help elucidate the mechanisms of osteoarthritis treatment with glucosamine. Evidence of beneficial cellular effects at clinically achievable concentrations will help validate the use of glucosamine for the treatment of OA.

Animal Health Component

50%

Research Effort Categories

Basic

50%

Applied

50%

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
305	3810	1020	100%

Knowledge Area
305 - Animal Physiological Processes;

Subject Of Investigation
3810 - Horses, ponies, and mules;

Field Of Science
1020 - Physiology;

Keywords

glucosamine

chondrocytes

synoviocytes

osteoarthritis

Goals / Objectives
Horses represent a major industry in Illinois and in the United States. Wastage due to lameness represents a large potential loss to horse owners, the agricultural industry, the Illinois state government, and the nation. Traditional therapies for treatment of osteoarthritis (OA), a major cause of lameness wastage in horses, have focused on non-steroidal anti-inflammatory drugs. While these drugs have been effective in reducing arthritis-related pain they do not reliably arrest progression of joint disease, and have been implicated in the development of clinically important side-effects such as gastrointestinal ulceration. In light of the current shortcomings of equine osteoarthritis (OA) therapy, further research on alternatives is necessary. Glucosamine treatment has shown promise, however prior in vitro research has not shown benefits at clinically achievable concentrations (in light of recent pharmacokinetic studies). In clinical use, chondrocytes are not exposed to concentrations of glucosamine routinely used in in vitro research. In addition, the responses of synoviocytes to glucosamine have not been thoroughly investigated despite the fact that these cells are important contributors to the pathophysiology of OA. To address these issues our objectives in this study are to determine the effects of glucosamine on inflammatory mediator release, degradative enzyme release, and proteoglycan metabolism of cytokine-stimulated and non-stimulated equine chondrocytes and synoviocytes in vitro at clinically relevant concentrations.

Project Methods
The effects of glucosamine on inflammatory mediator release (PGE2, COX-2 expression, Nitric Oxide), degradative enzyme release (matrix metalloproteinases), and proteoglycan metabolism (new production and degradation) will be explored at clinically relevant glucosamine concentrations. The experiment will be performed on cells collected from the metacarpophalangeal and metatarsophalangeal joints of 6 horses. Tissue will be free of gross evidence of OA. Chondrocytes and synoviocytes in either a non-inflammatory (no Interleukin-1) or inflammatory (with Interleukin-1) environment will be treated with glucosamine at various clinically relevant concentrations in cell culture. Previously validated assays will be used to assess the above parameters.

Progress 10/01/05 to 09/30/06

Outputs
Osteoarthritis related joint pain affects a significant proportion of the equine population with resultant chronic pain, decreased mobility, decline in performance, reduction in quality of life for both animal and owner, and potentially significant owner expense. Glucosamine has been used as an alternative therapy for the treatment of arthritis with a growing body of evidence in support of its pain relieving and potentially chondroprotective properties. Prior research supports a role for glucosamine in the protection of cartilage matrix and chondrocyte metabolism, suggesting a possible mechanism whereby glucosamine may help alleviate clinical signs and possibly retard progression of OA. However, in vitro studies investigating the effects of glucosamine on cartilage have typically utilized concentrations in excess of those seen by joint tissues with clinical use. The realization that synovial fluid levels of glucosamine after oral administration at the currently recommended dosages likely do not achieve levels commonly utilized in in vitro research led us to investigate the effects of low-dose glucosamine on equine synoviocytes and chondrocytes. Our findings suggest that glucosamine has limited effects on equine articular cells, although we did observe some potentially beneficial anti-inflammatory effects at low concentrations. We have begun to more narrowly define what effects glucosamine may have on joint tissue within a relevant concentration range. It is becoming apparent that effects observed at previously studied high concentrations may not be consistent with effects at lower concentrations. Other authors have recently investigated the effects of clinically relevant concentrations of glucosamine, alone and in combination with chondroitin sulfate, on chondrocytes from several species. These studies have found varying degrees of efficacy, depending on the specific dose and outcome parameter measured. Further work is needed to more fully define the effects of glucosamine alone and in combination with other agents. Furthermore, additional in vivo work is also needed to characterize tissue concentrations, effects, and the ultimate fate of orally administered glucosamine-containing products.

Impacts
There has been much debate regarding the utility of glucosamine in the treatment of joint disease. This project has supplied some support for the use of glucosamine at clinically achievable concentrations, suggesting that it may have limited but potentially beneficial effects at commonly used dosages.

Publications

• No publications reported this period