Facilitative Glucose Transporters in Articular Chondrocytes: Expression, Distribution and Functional Regulation of GLUT Isoforms by Hypoxia, Hypoxia Mimetics

Articular cartilage is a unique and highly specialized avascular connective tissue in which the availability of oxygen and glucose is significantly lower than synovial fluid and plasma. Glucose is an essential source of energy during embryonic growth and fetal development and is vital for mesenchymal cell differentiation, chondrogenesis and skeletal morphogenesis. Glucose is an important metabolic fuel for differentiated chondrocytes during post-natal development and in adult articular cartilage and is a common structural precursor for the synthesis of extracellular matrix glycosaminoglycans. Glucose metabolism is critical for growth plate chondrocytes which participate in long bone growth. Glucose concentrations in articular cartilage can fluctuate depending on age, physical activity and endocrine status. Chondrocytes are glycolytic cells and must be able to sense the concentration of oxygen and glucose in the extracellular matrix and respond appropriately by adjusting cellular metabolism. Consequently chondrocytes must have the capacity to survive in an extracellular matrix with limited nutrients and low oxygen tensions. Published data from our laboratories suggest that chondrocytes express multiple isoforms of the GLUT/SLC2A family of glucose/polyol transporters. In other tissues GLUT proteins are expressed in a cell-specific manner, exhibit distinct kinetic properties, and are developmentally regulated. Several GLUTs expressed in chondrocytes are regulated by hypoxia, hypoxia mimetics, metabolic hormones and pro-inflammatory cytokines. In this multidisciplinary article we review the molecular and morphological aspects of GLUT expression and function in chondrocytes and their mesenchymal and embryonic stem cell precursors and propose key roles for these proteins in glucose sensing and metabolic regulation in cartilage.