What drives osteoclasts to begin to fuse?

Monocytes and macrophages differentiate into bone-resorbing osteoclasts (OCLs) under the direction of the cytokines M-CSF and RANKL. It is believed that RANKL induces a small fraction of monocytes to become “Founder” cells, which have the capacity to initiate cell-cell fusion. The remaining cells are “Follower” cells, which can fuse with Founder cells but cannot initiate the process themselves. Both classes of cells are morphologically identical, and the molecular differences between them are unknown. We are devising methods to isolate Founder cells and to study the molecular basis for their ability to initiate fusion in order to better understand the initial stages of OCL formation.