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Elevated nutrient availability enhances chondrocyte metabolism and biosynthesis in tissue-engineered cartilage
Roberto Tarantino1, Halie Mei Jensen2, Stephen D Waldman1
1Department of Chemical Engineering, Toronto Metropolitan University, Toronto, Ontario, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada; Institute of Biomedical Engineering, Science and Technology (iBEST), Unity Health and Toronto Metropolitan University, Toronto, Ontario, Canada.
Osteoarthritis and Cartilage
|April 14, 2024
Summary
Increased media availability boosts chondrocyte extracellular matrix (ECM) production and alters metabolism. Glutamine metabolism is crucial for ECM accumulation in these cells.
Area of Science:
- Cell Biology
- Biochemistry
- Biotechnology
Background:
- Chondrocytes typically utilize anaerobic metabolism.
- Upregulated biosynthetic activity occurs under mixed aerobic-anaerobic conditions.
- Previous studies linked maximal ECM accumulation to a metabolic transition point.
Purpose of the Study:
- To investigate the impact of further increased media availability on chondrocyte metabolism.
- To determine the effect on extracellular matrix (ECM) synthesis.
- To explore metabolic phenotype changes in response to enhanced nutrient supply.
Main Methods:
- Primary bovine chondrocytes cultured in 3D high-density systems.
- Varied media availability (4-16 mL/10^6 cells).
- Biochemical assays and 13C-metabolic flux analysis (13C-MFA) used to assess ECM and metabolism.
Main Results:
- Higher media volumes increased cartilaginous ECM (collagen, proteoglycans) and cellularity.
- Elevated media availability enhanced glucose and glutamine metabolism, increasing anaerobic activity.
- 13C-MFA revealed upregulation of glycolysis, TCA cycle, and other central carbon pathways; glutamine carbons were utilized in the TCA cycle.
Conclusions:
- Increased media availability enhances ECM synthesis and significantly alters chondrocyte metabolic phenotype.
- Glutamine metabolism is vital for chondrocytes, with increased glutamine use correlating to greater ECM accumulation.
