RANK Is the Essential Signaling Receptor for Osteoclast Differentiation Factor in Osteoclastogenesis

• Published in: Biochemical and biophysical research communications Vol. 253; no. 2; pp. 395 - 400
• Main Authors: Nakagawa, Nobuaki, Kinosaki, Masahiko, Yamaguchi, Kyoji, Shima, Nobuyuki, Yasuda, Hisataka, Yano, Kazuki, Morinaga, Tomonori, Higashio, Kanji
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.12.1998
• Subjects: Animals; Bone and Bones - metabolism; Bone Resorption - immunology; Bone Resorption - metabolism; Carrier Proteins; Cells, Cultured; Cercopithecus aethiops; Cloning, Molecular; COS Cells; Gene Expression Regulation; Immune Sera - pharmacology; Immunoglobulin Fab Fragments - pharmacology; Male; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - physiology; Mice; NF-kappa B - metabolism; Osteoclasts - immunology; Osteoclasts - metabolism; Osteoclasts - physiology; Rabbits; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - immunology; Receptors, Tumor Necrosis Factor - physiology; Signal Transduction - physiology; Solubility; Space life sciences; Stem Cells - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1998.9788

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.