RANKL- and ROS-activated signals affecting the genesis and lifespan of osteoclasts

In osteoclast precursors, RANKL-induced activation of RANK stimulates NFATc1 activation via cFOS/AP-1 and CREB. In addition, mitochondria biogenesis coupled with activation of the transferrin receptor by the iron-transferrin complex stimulates mitochondria respiration and ROS production, which are also essential for osteoclast activation.

RANKL: RANK ligand; ROS: reactive oxygen species; Fe: iron; Tf: transferrin; RANK: receptor activator of nuclear factor kappa-B; TfR1: transferrin receptor 1; CREB: cAMP response element–binding protein; NFATc1: nuclear factor of activated T cells 1; PGC-1Β: peroxisome proliferator–activated receptor-gamma coactivator 1-beta.

Reprinted by permission from: Macmillan Publishers Ltd: Ishii KA, Fumoto T, Iwai K, et al. Coordination of PGC-1beta and iron uptake in mitochondrial biogenesis and osteoclast activation. Nat Med 2009; 15:259. Copyright © 2009.

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RANKL- and ROS-activated signals affecting the genesis and lifespan of osteoclasts