Fig. 2.

The “find me” message from apoptotic osteocytes. Under fatigue failure, osteocytes undergo apoptosis, whereas the osteocytes surrounding the apoptotic osteocytes, the “bystander osteocytes”, show upregulation of the antiapoptotic protein BcL-2, which protects them from death. Apoptotic osteocytes activate the Panx1/P2XR pathway to induce the release of ATP into the extracellular compartment as a specific “find me” signal. ATP binds P2Y2 receptors on bystander osteocytes, which in turn produce and release RANKL at the interface with the bone marrow. RANKL promotes the recruitment of osteoclast progenitors and osteoclastogenesis