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.

Integrins are heterodimeric integral membrane proteins made up of a and ss subunits. At least 18 a and 8 ss subunit genes have been described in mammals. Integrin family members are plasma membrane receptors involved in cell adhesion and active as intra- and extracellular signalling molecules in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic spread of tumor cells. Integrin beta 1 (ss1-integrin) the protein encoded by the ITGB1 gene (also known as CD29 and VLAB) is a multi-functional protein involved in cell-matrix adhesion, cell signalling, cellular defense, cell adhesion, protein binding, protein heterodimerization and receptor-mediated activity. It is highly expressed in the human body (17.4 times higher than the average gene in the last updated revision of the human genome). The extracellular matrix (ECM) of articular cartilage is a unique environment. Interactions between chondrocytes and the ECM regulate many biological processes important to homeostasis and repair of articular cartilage including cell attachment, growth, differentiation, and survival. The ss1-integrin family of cell surface receptors appears to play a major role in mediating cell-matrix interactions that are important in regulating these fundamental processes. Chondrocyte mechanoreceptors have been proposed to incorporate ss1-integrins and mechanosensitive ion channels which link with key ECM, cytoskeletal and signalling proteins to maintain the chondrocyte phenotype, prevent chondrocyte apoptosis and regulate chondrocyte-specific gene expression.