Early estrogen-induced gene 1, a novel RANK signaling component, is essential for osteoclastogenesis

The receptor activator of NF-KB （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...

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Bibliographic Details
Published in:Cell research 2013-04, Vol.23 (4), p.524-536
Main Authors: Choi, Han Kyoung, Kang, Hye Ri, Jung, Eutteum, Kim, Tae Eon, Lin, Jing Jing, Lee, Soo Young
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Animals
Bone Marrow Cells - cytology
Bone Marrow Cells - drug effects
Bone Marrow Cells - metabolism
Bone Resorption - genetics
Bone Resorption - metabolism
Bone Resorption - pathology
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Differentiation
Cell Line
Gene Expression Regulation - drug effects
Humans
Mice
NF-κB
NFATC Transcription Factors - genetics
NFATC Transcription Factors - metabolism
Original
Osteoclasts - cytology
Osteoclasts - drug effects
Osteoclasts - metabolism
Peptides - pharmacology
Phospholipase C gamma - genetics
Phospholipase C gamma - metabolism
Phosphorylation - drug effects
Protein Binding
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - metabolism
Proteins
RANK
RANK Ligand - genetics
RANK Ligand - metabolism
Receptor Activator of Nuclear Factor-kappa B - antagonists & inhibitors
Receptor Activator of Nuclear Factor-kappa B - genetics
Receptor Activator of Nuclear Factor-kappa B - metabolism
Signal Transduction - drug effects
信令
早期基因
破骨细胞
组件
诱导基因
雌激素
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Summary:The receptor activator of NF-KB （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 inter- acts with RANK and further associates with Gab2, PLC3,2 and Tee/Btk kinases upon RANKL stimulation. EEIG1 positively regulates RANKL-induced osteoclast formation, likely due to its ability to facilitate RANKL-stimulated PLCv2 phosphorylation and NFATcl 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.
ISSN:1001-0602
1748-7838
DOI:10.1038/cr.2013.33