Identity of Osteoclastogenesis Inhibitory Factor (OCIF) and Osteoprotegerin (OPG): A Mechanism by Which OPG/OCIF Inhibits Osteoclastogenesis in Vitro

Endocrinology. 1998 Mar;139(3):1329-37. doi: 10.1210/endo.139.3.5837.

Abstract

The morphogenesis and remodeling of bone depends on the integrated activity of osteoblasts that form bone and osteoclasts that resorb bone. We previously reported the isolation of a new cytokine termed osteoclastogenesis inhibitory factor, OCIF, which specifically inhibits osteoclast development. Here we report the cloning of a complementary DNA of human OCIF. OCIF is identical to osteoprotegerin (OPG), a soluble member of the tumor-necrosis factor receptor family that inhibits osteoclastogenesis. Recombinant human OPG/OCIF specifically acts on bone tissues and increases bone mineral density and bone volume associated with a decrease of active osteoclast number in normal rats. Osteoblasts or bone marrow-derived stromal cells support osteoclastogenesis through cell-to-cell interactions. A single class of high affinity binding sites for OPG/OCIF appears on a mouse stromal cell line, ST2, in response to 1,25-dihydroxyvitamin D3. An anti-OPG/OCIF antibody that blocks the binding abolishes the biological activity of OPG/OCIF. When the sites are blocked with OPG/OCIF, ST2 cells fail to support osteoclastogenesis. These results suggest that the sites are involved in cell-to-cell signaling between stromal cells and osteoclast progenitors and that OPG/OCIF inhibits osteoclastogenesis by interrupting the signaling through the sites.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bone Density / drug effects
  • Bone Remodeling
  • Cells, Cultured
  • Cloning, Molecular
  • Glycoproteins / genetics
  • Glycoproteins / physiology*
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Osteoclasts / drug effects
  • Osteoclasts / physiology*
  • Osteoprotegerin
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cytoplasmic and Nuclear*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / physiology*
  • Recombinant Proteins / pharmacology

Substances

  • Glycoproteins
  • Osteoprotegerin
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • TNFRSF11B protein, human
  • Tnfrsf11b protein, mouse
  • Tnfrsf11b protein, rat

Associated data

  • GENBANK/AB002146