Osteoprotegerin Ligand Is a Cytokine That Regulates Osteoclast Differentiation and Activation

Cell. 1998 Apr 17;93(2):165-76. doi: 10.1016/s0092-8674(00)81569-x.

Abstract

The ligand for osteoprotegerin has been identified, and it is a TNF-related cytokine that replaces the requirement for stromal cells, vitamin D3, and glucocorticoids in the coculture model of in vitro osteoclastogenesis. OPG ligand (OPGL) binds to a unique hematopoeitic progenitor cell that is committed to the osteoclast lineage and stimulates the rapid induction of genes that typify osteoclast development. OPGL directly activates isolated mature osteoclasts in vitro, and short-term administration into normal adult mice results in osteoclast activation associated with systemic hypercalcemia. These data suggest that OPGL is an osteoclast differentiation and activation factor. The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGL and OPG are key extracellular regulators of osteoclast development.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bone Resorption
  • Carrier Proteins*
  • Cell Differentiation
  • Cells, Cultured
  • Cloning, Molecular
  • Coculture Techniques
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Cytokines / pharmacology
  • Gene Expression Regulation, Developmental
  • Glycoproteins / metabolism*
  • Hematopoietic Stem Cells / cytology
  • Humans
  • Hypercalcemia
  • Ligands
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Membrane Glycoproteins*
  • Mice
  • Molecular Sequence Data
  • Organ Specificity
  • Osteoclasts / cytology*
  • Osteoclasts / metabolism*
  • Osteoprotegerin
  • Protein Binding
  • RANK Ligand
  • RNA, Messenger / analysis
  • Rats
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear*
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins

Substances

  • Carrier Proteins
  • Cytokines
  • Glycoproteins
  • Ligands
  • Membrane Glycoproteins
  • Osteoprotegerin
  • RANK Ligand
  • RNA, Messenger
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • Tnfrsf11a protein, mouse
  • Tnfrsf11b protein, mouse
  • Tnfrsf11b protein, rat
  • Tnfsf11 protein, mouse
  • Macrophage Colony-Stimulating Factor

Associated data

  • GENBANK/AF053712
  • GENBANK/AF053713