A RANKL-Inducible Gene Znf216 in Osteoclast Differentiation

Osteoclasts possess catabolic activity in mineralized tissues and are involved in bone remodeling coordinating with osteoblasts. Although the pathway using receptor and activator of NF-κ B (RANK) and its ligand, RANKL, is known to be essential for osteoclast differentiation, their precise mechanisms are not fully understood. Using DNA microarray technology, we searched for genes that were up-regulated after RANKL stimulation in the macrophage cell line, RAW264.7 cells. A gene, Znf216, which encodes a zinc-finger protein, was detected among those genes up-regulated after RANKL stimulation. Expression of Znf216 was also induced by other cytokines such as TNFα and IL-1β. Although ectopic expression of full-length ZNF216 abrogated osteoclast differentiation, its truncated forms accelerated it. No significant inhibitory effect on the NF-κ B pathway was observed, however. These results suggest that ZNF216 is a potent inhibitory factor for osteoclast differentiation and that the mechanism is unlikely due to direct attenuation of the NF-κ B pathway.