Abstract: Understanding the expression of catabolic and anabolic genes during osteoarthritis progression should help to identify the major mediators of the disease. Objective: To compare the cytokine and anabolic marker concentrations in synovium, synovial fluid and cartilage between normal and osteoarthritic joints. Methods: Carpi from horses age 2-11 years were used. Tissues were harvested at the time of surgery or euthanasia, and RNA was isolated for RT-PCR analysis. Tumour necrosis factor alpha (TNFα), interleukin-1beta (IL-1β), aggrecanase 1 (ADAMTS-4), aggrecanase 2 (ADAMTS-5), matrix metalloproteinase-13 (MMP-13), interleukin 17 (IL-17) and collagen type I alpha 1(Col-1) expression were determined in synovium. TNFα, IL-1β, ADAMTS-4, ADAMTS-5, MMP-13, IL-17, collagen type IIB (Col-2B), and aggrecan expression were determined in cartilage. TNFα concentration in the synovial fluid was determined by enzyme-linked immunosorbent assay (ELISA). Results: Expression of TNFα, ADAMTS-5 and MMP-13 was significantly increased in synovial tissue from OA joints. Synovial membrane IL-1β abundance showed only moderate elevations in OA, without reaching significant levels. Cytokine expression was increased significantly in OA cartilage samples, particularly TNFα, IL-1β, ADAMTS-4 and MMP-13; and collagen type I expression was significantly increased in synovial tissues from OA groups. Collagen type II message was diminished in mild and moderate stages of OA, but rebounded to significant elevations in severely degenerate joints. Conversely, aggrecan levels significantly declined in cartilage from all OA groups. Synovial fluid TNFα peptide concentration was significantly increased in severe OA cases. Conclusions: TNFα was increased in all degrees of equine OA, and was abundantly expressed in synovial membrane and cartilage. IL-1β was overexpressed in OA cartilage, but not to a significant extent in synovium. Conclusions: Control of TNFα should be considered further as a target in the treatment of OA. ADAMTS-4 may be the primary aggrecanase causing cartilage breakdown in OA.
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The research article presents a study on the role of various enzymes and cytokines in osteoarthritis (OA) in horses. It highlights the clear difference in the concentrations of these components in normal and osteoarthritis-infected joints, providing insights for potential treatments.
Objective and Methods
The research aimed to understand the expression and concentration differences of catabolic and anabolic genes in synovium, synovial fluid, and cartilage between normal and osteoarthritic joints in horses.
The study used carpi from horses aged 2 to 11 years. The tissues were harvested, and RNA was isolated for RT-PCR analysis. Multiple mediators, including TNFα, IL-1β, ADAMTS-4, ADAMTS-5, MMP-13, IL-17, and different types of collagen, were examined.
In the synovium, TNFα concentration was determined by the enzyme-linked immunosorbent assay (ELISA).
Results
The study found increased expression of TNFα, ADAMTS-5, and MMP-13 in the synovial tissue of osteoarthritic joints. IL-1β showed only mild elevations in OA.
The OA cartilage samples showed significant elevations in cytokine expression, particularly TNFα, IL-1β, ADAMTS-4, and MMP-13. Collagen type I expression was significantly increased in synovial tissues from the OA groups.
In the early stages of OA, collagen type II expression was reduced but increased significantly in severely degenerated joints. In contrast, aggrecan levels declined in cartilage from all OA groups.
The concentration of TNFα in the synovial fluid was significantly increased in cases of severe OA.
Conclusions
The researchers concluded that TNFα was abundantly expressed in the synovial membrane and cartilage in all stages of equine osteoarthritis. It increased significantly in severe OA cases.
IL-1β was overexpressed in OA cartilage, but its elevation in synovia was not significant.
The control of TNFα could potentially be a target in the treatment of OA as its significant increase was seen in all stages of OA.
ADAMTS-4 might be considered the primary aggrecanase responsible for causing cartilage breakdown in OA, as its expression was significantly high in OA cartilage.
Cite This Article
APA
Kamm JL, Nixon AJ, Witte TH.
(2010).
Cytokine and catabolic enzyme expression in synovium, synovial fluid and articular cartilage of naturally osteoarthritic equine carpi.
Equine Vet J, 42(8), 693-699.
https://doi.org/10.1111/j.2042-3306.2010.00140.x
College of Veterinary Medicine, Cornell University, NY, USA.
Nixon, A J
Witte, T H
MeSH Terms
Animals
Cartilage, Articular / metabolism
Cytokines / genetics
Cytokines / metabolism
Endopeptidases / genetics
Endopeptidases / metabolism
Gene Expression Regulation / physiology
Horse Diseases / metabolism
Horses
Osteoarthritis / metabolism
Osteoarthritis / veterinary
Synovial Membrane / metabolism
Grant Funding
R01 AR055373 / NIAMS NIH HHS
R01 AR055373-01A2 / NIAMS NIH HHS
5R01-AR055373-01 / NIAMS NIH HHS
R01-AR055373 / NIAMS NIH HHS
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