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

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

MeSH terms

  • Animals
  • Bone Resorption / immunology
  • Bone Resorption / metabolism*
  • Bone and Bones / metabolism
  • COS Cells
  • Carrier Proteins*
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cloning, Molecular
  • 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*
  • RANK Ligand
  • Rabbits
  • 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
  • Stem Cells / metabolism


  • Carrier Proteins
  • Immune Sera
  • Immunoglobulin Fab Fragments
  • Membrane Glycoproteins
  • NF-kappa B
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse