A RANKL-inducible gene Znf216 in osteoclast differentiation

J Recept Signal Transduct Res. 2005;25(3):199-216. doi: 10.1080/10799890500240781.

Abstract

Osteoclasts possess catabolic activity in mineralized tissues and are involved in bone remodeling coordinating with osteoblasts. Although the pathway using receptor and activator of NF-kappa B (RANK) and its ligand, RANKL, is known to be essential for osteoclast differentiation, their precise mechanisms are not fully understood. Using DNA microarray technology, we searched for genes that were up-regulated after RANKL stimulation in the macrophage cell line, RAW264.7 cells. A gene, Znf216, which encodes a zinc-finger protein, was detected among those genes up-regulated after RANKL stimulation. Expression of Znf216 was also induced by other cytokines such as TNFalpha and IL-1beta. Although ectopic expression of full-length ZNF216 abrogated osteoclast differentiation, its truncated forms accelerated it. No significant inhibitory effect on the NF-kappa B pathway was observed, however. These results suggest that ZNF216 is a potent inhibitory factor for osteoclast differentiation and that the mechanism is unlikely due to direct attenuation of the NF-kappa B pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Carrier Proteins / metabolism*
  • Cell Differentiation
  • Cell Line
  • DNA / metabolism
  • DNA, Complementary / metabolism
  • Down-Regulation
  • Gene Expression Regulation
  • Genes, Reporter
  • Humans
  • Immunoblotting
  • Interleukin-1 / metabolism
  • Ligands
  • Macrophages / cytology
  • Macrophages / metabolism
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Monocytes / cytology
  • NF-kappa B / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Osteoblasts / metabolism
  • Osteoclasts / cytology*
  • Osteoclasts / metabolism
  • Plasmids / metabolism
  • Proteins / metabolism*
  • RANK Ligand
  • RNA / metabolism
  • Receptor Activator of Nuclear Factor-kappa B
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation*
  • Zinc Fingers
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Carrier Proteins
  • DNA, Complementary
  • Interleukin-1
  • Ligands
  • Membrane Glycoproteins
  • NF-kappa B
  • Proteins
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • TNFRSF11A protein, human
  • TNFSF11 protein, human
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • Tumor Necrosis Factor-alpha
  • ZFAND5 protein, human
  • RNA
  • DNA
  • p38 Mitogen-Activated Protein Kinases