Historically significant events in the discovery of RANK/RANKL/OPG

Core Tip

Core tip: The history of discovery of receptor activator of nuclear factor κB ligand began with the hypothesis that the osteoblast lineage controls osteoclast formation. The hypothesis was confirmed by experiments showing first, that osteoblastic cells were necessary for osteoclast activation, then some years later that osteoblasts were necessary for osteoclast formation in a contact-dependent process. Ultimate confirmation came from mouse genetics, discovering inhibition of osteoblast formation by a secreted tumor necrosis factor (TNF) ligand, followed by discovery of promotion of osteoclast formation by a membrane-bound member of the TNF ligand family that signalled through its receptor in hemopoietic cells to promote osteoclast formation.