The receptor activator of NF-kB (RANK) and ITAM-containing adaptors have been identified as essential factors involved in osteoclast formation and bone remodeling, but their mechanisms and interacting factors have not yet been fully identified. Here we report that early estrogen-induced gene 1 (EEIG1), a novel RANK ligand (RANKL)-inducible protein, physically interacts with RANK and further associates with Gab2, PLCg2, and Tec/Btk kinases by RANKL stimulation. Overexpression of EEIG1 enhances osteoclastogenesis, whereas small hairpin RNA (shRNA)-mediated EEIG1 silencing inhibits osteoclast formation, which results from impaired RANKL-mediated PLCg2 phosphorylation and NFATc1 induction. In addition, the inhibitory peptide designed to block RANKEEIG1 interaction showed decreased RANKL-induced bone destruction by reducing the numbers of osteoclasts. Hence, we have identified a novel RANK signaling component, which controls RANK-mediated osteoclast formation and which may provide the molecular target for a new therapeutic strategy.
17 May 2014 - 20 May 2014