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Elevated Glucose Levels Preserve Glucose Uptake, Hyaluronan Production, and Low Glutamate Release Following Interleukin-1β Stimulation of Differentiated Chondrocytes.
- Source :
-
Cartilage [Cartilage] 2019 Oct; Vol. 10 (4), pp. 491-503. Date of Electronic Publication: 2018 Apr 27. - Publication Year :
- 2019
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Abstract
- Objective: 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.<br />Design: To create an OA model, we used equine chondrocytes from 4 individual horses that were differentiated into cartilage pellets in vitro 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.<br />Results: 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.<br />Conclusions: 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.
- Subjects :
- Animals
Cartilage, Articular cytology
Cartilage, Articular metabolism
Cell Differentiation physiology
Cells, Cultured
Extracellular Matrix metabolism
Gene Expression Regulation physiology
Glycolysis physiology
Horses
Hyaluronan Synthases biosynthesis
Hyaluronan Synthases genetics
Interleukin-1beta immunology
Chondrocytes metabolism
Glucose metabolism
Glutamic Acid metabolism
Hyaluronic Acid biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1947-6043
- Volume :
- 10
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cartilage
- Publication Type :
- Academic Journal
- Accession number :
- 29701083
- Full Text :
- https://doi.org/10.1177/1947603518770256