Fig. 8: Schematic overview of the role of the PPP during bone development.

Overview of the role of the PPP during chondrocyte proliferation and differentiation. Deletion of G6PDH, the rate-limiting enzyme of the oxPPP does not affect chondrocyte proliferation, as reversal of the non-oxPPP produces sufficient ribose-5-P for nucleotide synthesis. On the other hand, the oxPPP is necessary for the hypoxic differentiating chondrocytes, as the produced NADPH guarantees glutathione recycling, which in turn will scavenge ROS formed during oxidative protein folding. The PPP thus controls proteostasis and prevents ferroptosis.