title: RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis.
abstract: 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.
authors.affiliation: Research Institute of Life Science, Snow Brand Milk Products Co., Ltd., Tochigi, Japan. fvbd7042@mb.infoweb.ne.jp
authors.forename: N
authors.initials: N
authors.lastname: Nakagawa
authors.forename: M
authors.initials: M
authors.lastname: Kinosaki
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: N
authors.initials: N
authors.lastname: Shima
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: T
authors.initials: T
authors.lastname: Morinaga
authors.forename: K
authors.initials: K
authors.lastname: Higashio
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000276:immunology / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D007106:Immune Sera / Q000494:pharmacology; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010010:Osteoclasts / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D053245:RANK Ligand; D011817:Rabbits; D053246:Receptor Activator of Nuclear Factor-kappa B; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D012995:Solubility; D013234:Stem Cells / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D007106:Immune Sera; D007140:Immunoglobulin Fab Fragments; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse