Figure 4:

Glucose metabolism is altered by injury and partially rescued by Cdk9 inhibition. After joint injury and treatment with the Cdk9 inhibitor flavopiridol, the upstream to downstream ratios of central-energy-related metabolites were examined via LC-MS to understand energy utilization. (A) Conceptual model of glucose utilization injury upregulated pentose phosphate activity (PPP) to produce nucleotides. Flavopiridol blocks this upregulation and increases glycolytic metabolism. (A) There was a single outlier (plotted) in the NADPH:NADP+ ratio data. Five out of six mice demonstrated increases in the NADPH:NADP+ ratio upon indicating increased flux through the pentose phosphate pathway, potentially to produce nucleotides for upregulated gene expression. (B) The ATP:ADP ratio was increased in the injured knees for both control and treated groups indicating increased glycolytic flux, consistent with hypoxic energy utilization within the joint. (C) There were no signifcant changes in the ratio of NAD+:NADH. (D) The ratio of GDP:GTP was unchanged indicating similar TCA-cycle energy utilization. Data from n = 6 mice. In panels B-E, lines connect data from the injured and contralateral knees of the same mouse for paired analyses, n=6 mice per condition.