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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.
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.
Publication Date: 2010-11-30 PubMed ID: 21117899DOI: 10.3109/03008207.2010.523803Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research looks into the impacts of high mobility group box protein (HMGB)-1, interleukin (IL)-1β, and IL-6 on horse joint chondrocytes (cartilage cells), focusing on contrasting responses in different anatomical locations with varying physical pressures. The authors discovered that the consequences of these proteins are not necessarily determined by the physical load on different portions of the joint, shedding light on how inflammation may contribute to osteoarthritis.
Investigation Methods
- The authors used three-dimensional (3D) cell cultures of chondrocytes collected from the dorsal radial facet (a heavily loaded region) and the palmar condyle (a less straining area) of the third carpal bone (a bone in the wrist) in horses.
- They evaluated the impact of these proteins in these chondrocytes by examining the expression of genes related to cartilage metabolism. They looked at factors including glycosaminoglycans (GAGs – a key molecule in cartilage), cartilage oligomeric matrix protein (COMP – another important molecule in cartilage), matrix metalloproteinase (MMP)-13 (an enzyme that can degrade cartilage) and aggrecan epitope CS 846 (a component of cartilage).
Results of the Study
- Treatment with IL-1β was found to upregulate the expression of versican (an extracellular matrix protein), matrix-degrading enzymes and TIMP-1 (an inhibitor of matrix-degrading enzymes). In contrast, it downregulated the expression of aggrecan (a key substance in cartilage) and collagen types I and II.
- The IL-1β-treated samples also showed less safranin O staining (indicating lower levels of GAGs), increased COMP immunostaining and higher concentrations of MMP-13, all indications of cartilage breakdown.
- The effects of IL-6 and HMGB-1 treatments were variable, but the researchers noted that the gene expression of Sox9 (a transcription factor important in chondrocyte development) was often upregulated, potentially signaling attempts to repair or maintain the matrix.
- Interestingly, the researchers did not find significant differences between the highly loaded DRF and the less loaded PC areas in response to the cytokines. This suggests that the degradation of the cartilage in osteoarthritis in horses is not determined by different responses to inflammatory mediators in different areas of the joint, a new insight into osteoarthritis development.
- Differences in gene expression for structural matrix proteins were noted between the DRF and PC areas in younger horses, suggesting varying chondrocyte productivity at different locations.
Conclusion
- The researchers concluded that IL-1β induced a strong catabolic (breakdown) response in the cartilage, while IL-6 and HMGB-1 had more of a slight anabolic (growth and repair) effect.
This work provides new insights into the cellular mechanisms that might contribute to osteoarthritis as well as the role of various cytokines and proteins in these processes. It may guide future studies on treatments for conditions like osteoarthritis.
Cite This Article
APA
Ley C, Svala E, Nilton A, Lindahl A, Eloranta ML, Ekman S, Skiöldebrand E.
(2010).
Effects of high mobility group box protein-1, interleukin-1β, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures.
Connect Tissue Res, 52(4), 290-300.
https://doi.org/10.3109/03008207.2010.523803 Publication
Researcher Affiliations
- Division of Pathology, Pharmacology and Toxicology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden. cecilia.ley@bvf.slu.se
MeSH Terms
- Aggrecans / metabolism
- Animals
- Cartilage, Articular / cytology
- Cartilage, Articular / metabolism
- Chondrocytes / drug effects
- Chondrocytes / metabolism
- Extracellular Matrix Proteins / metabolism
- Gene Expression / drug effects
- Glycoproteins / metabolism
- HMGB1 Protein / pharmacology
- Horses
- Interleukin-1beta / pharmacology
- Interleukin-6 / pharmacology
- Matrilin Proteins
- Matrix Metalloproteinase 13 / metabolism
Citations
This article has been cited 16 times.- Pezzanite LM, Chow L, Griffenhagen GM, Bass L, Goodrich LR, Impastato R, Dow S. Distinct differences in immunological properties of equine orthobiologics revealed by functional and transcriptomic analysis using an activated macrophage readout system. Front Vet Sci 2023;10:1109473.
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- Hansson E, Skiöldebrand E. Bupivacaine in combination with sildenafil (Viagra) and vitamin D3 have anti-inflammatory effects in osteoarthritic chondrocytes. Curr Res Pharmacol Drug Discov 2021;2:100066.
- Skiöldebrand E, Ley C, Björklund U, Lindahl A, Hansson E. Serotonin-evoked cytosolic Ca(2+) release and opioid receptor expression are upregulated in articular cartilage chondrocytes from osteoarthritic joints in horses. Vet Anim Sci 2019 Dec;8:100078.
- Shu Z, Miao X, Tang T, Zhan P, Zeng L, Jiang Y. The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation. Int J Mol Med 2020 Mar;45(3):769-778.
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- Wang L, Pawlak E, Johnson PJ, Belknap JK, Alfandari D, Black SJ. Effects of cleavage by a disintegrin and metalloproteinase with thrombospondin motifs-4 on gene expression and protein content of versican and aggrecan in the digital laminae of horses with starch gruel-induced laminitis. Am J Vet Res 2012 Jul;73(7):1047-56.
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