Elevated Glucose Levels Preserve Glucose Uptake, Hyaluronan Production, and Low Glutamate Release Following Interleukin-1β Stimulation of Differentiated Chondrocytes.
Abstract: Chondrocytes are responsible for remodeling and maintaining the structural and functional integrity of the cartilage extracellular matrix. Because of the absence of a vascular supply, chondrocytes survive in a relatively hypoxic environment and thus have limited regenerative capacity during conditions of cellular stress associated with inflammation and matrix degradation, such as osteoarthritis (OA). Glucose is essential to sustain chondrocyte metabolism and is a precursor for key matrix components. In this study, we investigated the importance of glucose as a fuel source for matrix repair during inflammation as well as the effect of glucose on inflammatory mediators associated with osteoarthritis. To create an OA model, we used equine chondrocytes from 4 individual horses that were differentiated into cartilage pellets followed by interleukin-1β (IL-1β) stimulation for 72 hours. The cells were kept at either normoglycemic conditions (5 mM glucose) or supraphysiological glucose concentrations (25 mM glucose) during the stimulation with IL-1β. We found that elevated glucose levels preserve glucose uptake, hyaluronan synthesis, and matrix integrity, as well as induce anti-inflammatory actions by maintaining low expression of Toll-like receptor-4 and low secretion of glutamate. Adequate supply of glucose to chondrocytes during conditions of inflammation and matrix degradation interrupts the detrimental inflammatory cycle and induces synthesis of hyaluronan, thereby promoting cartilage repair.
Publication Date: 2018-04-27 PubMed ID: 29701083PubMed Central: PMC6755873DOI: 10.1177/1947603518770256Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article investigates the role of glucose in protecting cartilage cells or chondrocytes during inflammation and matrix degradation, as seen in conditions like osteoarthritis. Elevated glucose levels were found to maintain glucose uptake, promote the synthesis of key cartilage components like hyaluronan, and reduce inflammatory actions.
Research Methodology
- The researchers first set up the study model using chondrocytes – cells responsible for maintaining the integrity of cartilage – from horses.
- These cells were differentiated into cartilage pellets and then subjected to stimulation with Interleukin-1β (IL-1β) for 72 hours to simulate the conditions of osteoarthritis. Interleukin-1β is known to play a key role in driving inflammation during osteoarthritis.
- During this process, the cells were kept under normal glucose conditions (5 mM glucose) or supra-physiological glucose concentrations (25 mM glucose) to examine the impact of glucose levels.
Key Findings
- The results of the study revealed that elevated glucose levels protected the chondrocytes during inflammation by preserving glucose uptake, bolstering the synthesis of hyaluronan (a substantial component of the cartilage matrix), and maintaining cartilage integrity.
- Moreover, high glucose levels exhibited anti-inflammatory effects by keeping the expression of Toll-like receptor-4, a protein often upregulated during inflammation, at a low level. They also led to low secretion of glutamate, implying reduced inflammation.
Implications
- The findings of this study stress the importance of glucose as an energy source that sustains chondrocyte metabolisms even under stressful, inflammatory conditions like osteoarthritis.
- High glucose levels disrupt detrimental inflammatory cycles and stimulate the production of hyaluronan, thereby contributing to the repair of cartilage, a property that can be potentially exploited in therapeutic strategies for osteoarthritis and similar conditions affecting cartilage.
Cite This Article
APA
Rotter Sopasakis V, Wickelgren R, Sukonina V, Brantsing C, Svala E, Hansson E, Enerbäck S, Lindahl A, Skiöldebrand E.
(2018).
Elevated Glucose Levels Preserve Glucose Uptake, Hyaluronan Production, and Low Glutamate Release Following Interleukin-1β Stimulation of Differentiated Chondrocytes.
Cartilage, 10(4), 491-503.
https://doi.org/10.1177/1947603518770256 Publication
Researcher Affiliations
- Department of Clinical Chemistry and Transfusion Medicine, University of Gothenburg, Gothenburg, Sweden.
- Department of Clinical Chemistry and Transfusion Medicine, University of Gothenburg, Gothenburg, Sweden.
- Department of Medical Biochemistry and Cell biology, University of Gothenburg, Gothenburg, Sweden.
- Department of Clinical Chemistry and Transfusion Medicine, University of Gothenburg, Gothenburg, Sweden.
- Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Gothenburg, Sweden.
- Department of Clinical Neuroscience, University of Gothenburg, Gothenburg, Sweden.
- Department of Medical Biochemistry and Cell biology, University of Gothenburg, Gothenburg, Sweden.
- Department of Clinical Chemistry and Transfusion Medicine, University of Gothenburg, Gothenburg, Sweden.
- Department of Clinical Chemistry and Transfusion Medicine, University of Gothenburg, Gothenburg, Sweden.
MeSH Terms
- Animals
- Cartilage, Articular / cytology
- Cartilage, Articular / metabolism
- Cell Differentiation / physiology
- Cells, Cultured
- Chondrocytes / metabolism
- Extracellular Matrix / metabolism
- Gene Expression Regulation / physiology
- Glucose / metabolism
- Glutamic Acid / metabolism
- Glycolysis / physiology
- Horses
- Hyaluronan Synthases / biosynthesis
- Hyaluronan Synthases / genetics
- Hyaluronic Acid / biosynthesis
- Interleukin-1beta / immunology
Conflict of Interest Statement
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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