CO-TREATMENT WITH HYLARTIN-V AND BETAMETHASONE ON INFLAMED CHONDROCYTES

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: ANIMAL HEALTH
• Reporting Frequency: Annual
• Accession No.: 0212456
• Project Start Date: Oct 1, 2007
• Project End Date: Sep 30, 2008
• 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
Corticosteroids and hyaluronic acid are frequently administered to horses with osteoarthritis to minimize pain and allow return to normal function. There are minimal scientific studies in horses to support the various co-treatments with hyaluronic acid (HA) and corticosteroids in an osteoarthritic joint. This study will evaluate the benefit of a high molecular weight HA and a short acting corticosteroid for osteoarthritis. This study should establish whether commonly used HA and corticosteroid products have a difference in efficacy when treating osteoarthritic joints. The scientific knowledge gained from the study should directly benefit the veterinary practitioner administering the intra-articular medications. In addition, all horse owners benefit by establishing whether the extra cost ($120.00 per dose) of a high molecular weight HA has any scientific merit. Finally, more horses should be treated with a high molecular weight HA and BSP if there is a clear benefit to co-treatment.

Animal Health Component

25%

Research Effort Categories

Basic

75%

Applied

25%

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

osteoarthritis

cartilage metabolism

intra-articular medications

hyaluronic acid

betamethasone sodium phosphate

Goals / Objectives
Previous work has shown minimal effect with treatment of a medium molecular weight HA (alone or in combination with a long acting corticosteroid) on normal chondrocytes. Our second study showed a protective effect on proteoglycan matrix catabolism using the same medications on inflamed chondrocytes. The latest study using a high andmolecular weight HA and an intermediate acting corticosteroid and showed additional beneficial effects on proteoglycan metabolism with no detrimental effects on chondrocyte viability that were noted in the previous studies using a long acting corticosteroid. To date, there have been no studies evaluating the effect of high molecular weight HAs and short acting corticosteroids. The purpose of this study is to evaluate the effects of co-treatment with a high molecular weight HA and a short acting corticosteroid (BSP) on an inflamed chondrocyte model. The objective is to establish dose dependent effects of a high molecular weight hyaluronic acid and a short acting corticosteroid on proteoglycan synthesis and degradation in equine chondrocytes harvested from articular cartilage treated with interleukin-1 (IL-1).

Project Methods
Equine cartilage chondrocytes will be maintained in a pellet culture supplemented with defined, chondrogenic medium. Chondrocyte pellets will be treated with IL-1 and varying doses of BSP, HA, both drugs (TA+BSP) or maintained as untreated controls. The effects of these treatments on chondrocyte pellet PG metabolism will be assayed by several methods. Pellet PG content and PG released into the medium will be measured using DMMB analysis. PG synthesis rates will be assayed by 35S metabolic labeling. PG degradation rates will be assayed by measurement of 35S-PG released into the culture medium. Aggrecan mRNA expression will be assayed by RT-PCR analysis. Effects of the treatments on cell number will be assessed by fluorometric measurement of DNA and by histological evaluation of representative chondrocyte pellet sections. The distribution of PGs in the pellets will be determined by safranin-O staining. These experiments will provide a comprehensive evaluation of the effects of a high molecular weight HA and a short acting corticosteroid on IL-1 induced PG catabolism in articular chondrocyte pellet cultures.

Progress 10/01/07 to 09/30/08

Outputs
OUTPUTS: "Co-treatment with Hylartin-V and Betamethasone on inflamed chondrocytes" by Stewart, A. and Durgam, S. has been submitted to ACVS for presentation in the resident's forum for 2009. PARTICIPANTS: This was a master's research project for Dr. Elysia Schaefer who is completing her combined equine surgery residency and master's program. TARGET AUDIENCES: This information will be greatly useful to owners of horses and veterinarians who treat horses with intra-articular medications. We hope the results of this project will cause more people to invest in medicating joints with Hylartin-V. These results add to previous studies we have done on the combination of hyaluronic acid and corticosteroids for the treatment of inflammed chondrocytes. However, in this study treatment with Betamethasone was not as useful as treatment with another corticosteroid, Triamcinalone. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
These results support the combined used of both Betamethasone and Hylartin-V. Hylartin-V worked to increase the chondrocyte pellet proteoglycan synthesis. In contrast, Betamethasone suppressed many of the inflammatory mediators evident with IL-1 treatment. This project has led to submission for a clinical trial using both corticosteroids, Betamethasone and Hyarltin-V. These results will be beneficial to owners of performance horses that require intra-articular injections to stay sound. In addition, veterinarians that treat the horses will gain better knowledge about the intra-articular medications they are using.

Publications

• No publications reported this period