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Inflammation in equine articular cartilage

the effect of cytokines in chondrocyte pellets and explants: two in vitro models

Svala, Emilia (2014). Inflammation in equine articular cartilage. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis Agriculturae Sueciae, 1652-6880 ; 2014:78
ISBN 978-91-576-8104-1
eISBN 978-91-576-8105-8
[Doctoral thesis]

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Osteoarthritis (OA) is the main reason for lameness in racehorses. OA is currently clinically diagnosed late in the disease process, when irreversible damages to the articular cartilage have become evident. Diagnostic biomarkers that can detect the disease before irreversible tissue damage and prior to the onset of clinical signs would be very desirable. These biomarkers could be used to monitor the progression of articular cartilage destruction, repair, and inflammatory status. In order to develop biomarkers, it is necessary to further elucidate the pathogenesis of OA. The initiation and development of OA involves inflammatory processes mediated by pro-inflammatory cytokines. The objective of this thesis was to investigate the influence of cytokines, known to be involved in OA development, on equine articular chondrocytes in vitro. The aim was to increase the knowledge of the complex molecular mechanisms of the extracellular matrix (ECM), which may be responsible for the development, and progression of OA.

Healthy equine articular cartilage was stimulated with cytokines (interleukin (IL)-1β, HMGB-1, and IL-6) in two in vitro models (explants and three-dimensional pellet cultures). Analyses were performed by: immunohistochemistry, immunoassays (ELISAs, Western blot), biochemical assays (glycosaminoglycan content), quantification of gene expression, and quantitative proteomics. Additionally, synovial fluid collected from horses with healthy or OA joints was analysed with regard to content and glycosylation profile of lubricin.

Our studies showed that IL-1β induced a catabolic response in ECM-related genes and proteins. A time-dependent release of ECM proteins from equine explants was also detected. HMGB-1 stimulation of chondrocyte pellets indicated a promotion of chondrocyte differentiation or increased metabolic activity of chondrocytes. IL-6 stimulation of chondrocyte pellets inhibited the canonical Wnt-signalling pathway and upregulated the gene expression of growth differentiation factor (GDF)-5. The O-glycosylation profile of lubricin in synovial fluid was different for equine joints with OA compared to the normal joints/controls. Additionally, an endogenous cleavage site of lubricin was found both in vitro and in vivo.

The results from this thesis confirm IL-1β as a master cytokine in equine articular cartilage destruction. Furthermore the results indicate that IL-6 has a regulatory or protective role on articular cartilage metabolism. The results from the in vitro studies of equine articular cartilage render novel findings regarding the detailed and time-dependent ECM protein release caused by cytokines involved in OA. This knowledge can be used for the development of diagnostic biomarkers of early OA in vivo.

Authors/Creators:Svala, Emilia
Title:Inflammation in equine articular cartilage
Subtitle:the effect of cytokines in chondrocyte pellets and explants: two in vitro models
Series Name/Journal:Acta Universitatis Agriculturae Sueciae
Year of publishing :October 2014
Number of Pages:93
I.Ley, C., Svala, E., Nilton, A., Lindahl, A., Eloranta, ML., Ekman, S. and Skiöldebrand, E. (2011). Effects of high mobility group box protein-1, interleukin-1β, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures. Connective Tissue Research 52(4), 290-300.
II.Svala, E., Thorfve, A., Ley, C., Henriksson, HB., Synnergren, J., Lindahl, A., Ekman, S. and Skiöldebrand, E. (2014). Effects of interleukin-6 and interleukin-1β on expression of growth differentiation factor-5 and Wnt signaling pathway genes in equine chondrocytes. American Journal of Veterinary Research 75(2), 132-140.
III.Svala, E., Löfgren, M., Sihlbom, C., Rüetschi, U., Lindahl, A., Ekman, S. and Skiöldebrand, E. (2014). An inflammatory equine model demonstrates dynamic changes of immune response and cartilage matrix molecule degradation in vitro. (submitted)
IV.Svala, E*., Jin, C*., Rüetschi, U., Ekman, S., Lindahl, A., Karlsson, N., and Skiöldebrand, E. (2014). Characterization of lubricin in synovial fluid from horses with osteoarthritis. (In manuscript).
Place of Publication:Uppsala
Publisher:Department of Biomedicine and Veterinary Public Health, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-576-8104-1
ISBN for electronic version:978-91-576-8105-8
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L74 Miscellaneous animal disorders
X Agricola extesions > X30 Life sciences
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Pathobiology
Agrovoc terms:racehorses, osteoarthritis, pathogenesis, inflammation, cartilage, cytokines, interleukins, in vitro experimentation, analytical methods, diagnosis
Keywords:articular chondrocytes, in vitro, cytokines, osteoarthritis, horse, IL-1b, IL-6, inflammation, extra cellular cartilage matrix
Permanent URL:
ID Code:11602
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Biomedical Sciences and Veterinary Public Health
External funders:FORMAS and Stiftelsen Hästforskning
Deposited By: Emilia Svala
Deposited On:30 Oct 2014 07:20
Metadata Last Modified:02 Dec 2014 11:09

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