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Effects of high mobility group box protein-1, interleukin-1β, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures.

Journal article
Authors Cecilia Ley
Emilia Svala
Anna Nilton
Anders Lindahl
Maija-Leena Eloranta
Stina Ekman
Eva Skiöldebrand
Published in Connective tissue research
Volume 52
Issue 4
Pages 290-300
ISSN 1607-8438
Publication year 2011
Published at Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Institute of Biomedicine
Pages 290-300
Language en
Links dx.doi.org/10.3109/03008207.2010.52...
Keywords Aggrecans, metabolism, Animals, Cartilage, Articular, cytology, metabolism, Chondrocytes, drug effects, metabolism, Extracellular Matrix Proteins, metabolism, Gene Expression, drug effects, Glycoproteins, metabolism, HMGB1 Protein, pharmacology, Horses, Interleukin-1beta, pharmacology, Interleukin-6, pharmacology, Matrix Metalloproteinase 13, metabolism
Subject categories Veterinary Science, Biochemistry and clinical chemistry

Abstract

The effects of high mobility group box protein (HMGB)-1, interleukin (IL)-1β, and IL-6 on equine articular chondrocytes were investigated, with emphasis on detecting differences between anatomical sites exposed to different loading in vivo, using three-dimensional (3D) cell cultures established with chondrocytes from dorsal radial facet (DRF, highly loaded) and palmar condyle (PC, less loaded) of the third carpal bone (C3). Expression of important genes involved in cartilage metabolism, presence of glycosaminoglycans and cartilage oligomeric matrix protein (COMP) in pellets, and concentrations of matrix metalloproteinase (MMP)-13 and aggrecan epitope CS 846 were evaluated. Compared to controls, IL-1β treatment increased gene expression of versican, matrix-degrading enzymes, and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased aggrecan and collagen type I and type II expression. In addition, IL-1β-treated pellets showed decreased safranin O staining and increased COMP immunostaining and MMP-13 concentrations in culture supernatants. Effects of IL-6 and HMGB-1 on gene expression were variable, although upregulation of Sry-related high-mobility group box 9 (Sox9) was often present and statistically increased in HMGB-1-treated pellets. Response to cytokines rarely differed between DRF and PC pellets. Thus, site-associated cartilage deterioration in equine carpal osteoarthritis (OA) is not explained by topographically different responses to inflammatory mediators. Differences in gene expressions of structural matrix proteins in untreated DRF and PC pellets were noted in the youngest horses, which may indicate differences in the chondrocytes potential to produce matrix in vivo. Overall, a strong catabolic response was induced by IL-1β, whereas slight anabolic effects were induced by IL-6 and HMGB-1.

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