Figure 4. Osteoclastogenesis can be induced not only by RANKL, but also by TNF-, both members of the TNF ligand superfamily. The prerequisite for TNF--induced osteoclast formation is the presence of permissive amounts of RANKL. The mechanisms involved in the effect of TNF- on osteoclast formation involves enhanced expression of IL-1 in both osteoblasts/stromal cells (A) and in osteoclast progenitor cells (B), as well as increased RANK expression in the osteoclast progenitor cells (B).