Galactose-induced mitochondrial respiration reduces hypoxia-inducible factor 2α (HIF-2α) expression and signaling. (A) Nuclear expression of HIF-2α expression was evaluated after 1 or 5 days of glucose versus galactose treatment. Twenty-four hours of cobalt chloride (CoCl2) treatment stabilized HIF-2α. Five days of galactose treatment dramatically reduced the nuclear expression of HIF-2α in CoCl2-stabilized samples (n = 3). (B) Five days of galactose treatment also reduced the expression of EPAS1, the gene that encodes HIF-2α, but not HIF1 (n = 5). (C) The expression of multiple HIF-2α target genes, including NOS2, PTGS2, and MMP13, was also reduced after 5 days of a galactose culture. Results from galactose-treated chondrocytes were normalized to those from glucose samples to represent the fold induction in response to galactose. Bars represent mean ± standard error of the mean. *P <0.05, **P <0.01, and ***P <0.001 between glucose and galactose.