Deletion of Glut1 in early postnatal cartilage reprograms chondrocytes toward enhanced glutamine oxidation
Year: 2021
Type: article
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.
Source: Bone Research
Authors: Cuicui Wang, Jun Ying, Xiangfeng Niu, Xiaofei Li, Gary J. Patti, Jie Shen, Regis J. O’Keefe
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,890
Funders: U.S. Department of Health and Human Services, National Institutes of Health, Musculoskeletal Research Center, Washington University in St. Louis, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G151374072, G2310844859, G2753630130, G2775599718, G3169444214, G4365017791, Core Center for Musculoskeletal Biology and Medicine, A Comprehensive Platform for High-Throughput Profiling of the Human Reference Metabolome, G4790721331, G500294632, G5696530169, G5842963987, G6992116998, G817921940, Epigenetic Regulation of Bone Regeneration in Inflammatory Disease, G8885355438, G9000080375, G9000161266, G9000206903, Metabolic Regulation of Articular Cartilage and Joint Homeostasis, Washington University Nutrition Obesity Research Center, Epigenetic Regulation in Cartilage Tissue, Targeting angiogenesis for fracture nonunion treatment under inflammatory diseases
OpenAlex ID: W3193894491