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Biochem Biophys Res Commun. 1998 Dec 18;253(2):395-400.

RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis.

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Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan.


Osteoclast differentiation factor (ODF) is a ligand for osteoclastogenesis-inhibitory factor/osteoprotegerin (OCIF/OPG), and mediates an essential signal for osteoclastogenesis. Soluble-form ODF binds directly to osteoclast progenitors, suggesting the presence of a membrane-bound receptor for ODF (ODFR) on the cells. To understand the ODF-mediated signal transduction mechanism in osteoclastogenesis, we molecularly cloned ODFR from a mouse macrophage-like osteoclast progenitor cell line, C7. Nucleotide sequence analysis revealed that ODFR is identical to RANK, a recently identified member of the tumor necrosis factor receptor (TNFR) family, which is involved in the regulation of dendritic cell function. A polyclonal antibody against the extracellular domain of RANK induced osteoclastogenesis in the presence of macrophage colony-stimulating factor (M-CSF). In contrast, both a genetically engineered soluble RANK and Fab fragment of the antibody blocked the binding of ODF to RANK and ODF-mediated osteoclastogenesis. These results indicate that RANK is the signaling receptor essential for ODF-mediated osteoclastogenesis.

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