Figure 6. Modulation of the PHD/VHL/HIF pathway is sufficient to induce EPO production in adult bone and protect mice from anemia.
A. Augmented HIF signaling in osteoblasts protects mice from anemia. Percent hematocrit in 8-week-old OSX-Cre mice 48 hours after initial phenylhydrazine (PHZ) treatment ( n = 5 in each group). * indicate a statically difference compared to untreated OSX-Control mice as determined by Students t test (p<0.05). B. Pharmacologic inhibition of PHDs induces EPO expression in adult bone. EPO mRNA expression in 8-week-old bone 7 hours following intra-femoral injection of saline or DMOG ( n = 3 in saline and n = 3 in DMOG groups). C. Genetic inhibition of PHD1/2/3 activates Epo expression in bone. EPO mRNA expression in 8 week old OSX-Cre mutant mice ( n = 5 per group). D. Prolyl hydroxylase inhibition in osteoblasts increases hematocrit in 8-weekold mice ( n = 5 per group). Data are represented as mean +/− SEM.