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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 postnatal 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 proinflammatory cytokines. In this multidisciplinary text 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.

Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left-sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30–50 times more frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes. We also showed that genome-wide copy number variation is increased in TS and identify a common copy number variant (CNV) in chromosome 12p13.31 that is associated with LSL with an odds ratio of 3.7. This CNV contains three protein-coding genes (SLC2A3, SLC2A14, and NANOGP1) and was previously implicated in congenital heart defects in the 22q11 deletion syndrome. In addition, we identified a subset of rare and recurrent CNVs that are also enriched in non-syndromic BAV cases. These observations support our hypothesis that X chromosome and autosomal variants affecting cardiac developmental genes may interact to cause the increased prevalence of LSL in TS. © 2016 Wiley Periodicals, Inc.