Deletion of Glut1 in early postnatal cartilage reprograms chondrocytes toward enhanced glutamine oxidation
Open Access
- 23 August 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Bone Research
- Vol. 9 (1), 1-14
- https://doi.org/10.1038/s41413-021-00153-1
Abstract
Glucose metabolism is fundamental for the functions of all tissues, including cartilage. Despite the emerging evidence related to glucose metabolism in the regulation of prenatal cartilage development, little is known about the role of glucose metabolism and its biochemical basis in postnatal cartilage growth and homeostasis. We show here that genetic deletion of the glucose transporter Glut1 in postnatal cartilage impairs cell proliferation and matrix production in growth plate (GPs) but paradoxically increases cartilage remnants in the metaphysis, resulting in shortening of long bones. On the other hand, articular cartilage (AC) with Glut1 deficiency presents diminished cellularity and loss of proteoglycans, which ultimately progress to cartilage fibrosis. Moreover, predisposition to Glut1 deficiency severely exacerbates injury-induced osteoarthritis. Regardless of the disparities in glucose metabolism between GP and AC chondrocytes under normal conditions, both types of chondrocytes demonstrate metabolic plasticity to enhance glutamine utilization and oxidation in the absence of glucose availability. However, uncontrolled glutamine flux causes collagen overmodification, thus affecting extracellular matrix remodeling in both cartilage compartments. These results uncover the pivotal and distinct roles of Glut1-mediated glucose metabolism in two of the postnatal cartilage compartments and link some cartilage abnormalities to altered glucose/glutamine metabolism.Keywords
Funding Information
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (U01CA235482)
- U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR075860)
This publication has 60 references indexed in Scilit:
- Effects of In Vitro Low Oxygen Tension Preconditioning of Adipose Stromal Cells on Their In Vivo Chondrogenic Potential: Application in Cartilage Tissue RepairPLOS ONE, 2013
- Cancer Cell Metabolism: One Hallmark, Many FacesCancer Discovery, 2012
- Mitochondrial electron transport and glycolysis are coupled in articular cartilageOsteoarthritis and Cartilage, 2012
- Recent progress in understanding molecular mechanisms of cartilage degeneration during osteoarthritisAnnals of the New York Academy of Sciences, 2011
- A robust and high-throughput Cre reporting and characterization system for the whole mouse brainNature Neuroscience, 2009
- Understanding the Warburg Effect: The Metabolic Requirements of Cell ProliferationScience, 2009
- Regulation of chondrogenesis and chondrocyte differentiation by stressJCI Insight, 2008
- Optimized extraction of glycosaminoglycans from normal and osteoarthritic cartilage for glycomics profilingGlycobiology, 2006
- Mechanisms of synovial joint and articular cartilage formation: Recent advances, but many lingering mysteriesBirth Defects Research Part C: Embryo Today: Reviews, 2005
- Developmental regulation of the growth plateNature, 2003