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Early estrogen-induced gene 1, a novel RANK signaling component, is essential for osteoclastogenesis
- Early estrogen-induced gene 1, a novel RANK signaling component, is essential for osteoclastogenesis
- Choi H.K.; Kang H.R.; Jung E.; Kim T.E.; Lin J.J.; Lee S.Y.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Cell Research
- vol. 23, no. 4, pp. 524 - 536
- SCI; SCIE; SCOPUS
- The receptor activator of NF-κB (RANK) and immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptors are essential factors involved in regulating osteoclast formation and bone remodeling. Here, we identify early estrogen-induced gene 1 (EEIG1) as a novel RANK ligand (RANKL)-inducible protein that physically interacts with RANK and further associates with Gab2, PLCγ2 and Tec/Btk kinases upon RANKL stimulation. EEIG1 positively regulates RANKL-induced osteoclast formation, likely due to its ability to facilitate RANKL-stimulated PLCγ2 phosphorylation and NFATc1 induction. In addition, an inhibitory peptide designed to block RANK-EEIG1 interaction inhibited RANKL-induced bone destruction by reducing osteoclast formation. Together, our results identify EEIG1 as a novel RANK signaling component controlling RANK-mediated osteoclast formation, and suggest that targeting EEIG1 might represent a new therapeutic strategy for the treatment of pathological bone resorption. © 2013 IBCB, SIBS, CAS All rights reserved.
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