The hematopoietic transcription factor PU.1 regulates RANK gene expression in myeloid progenitors

Biochem Biophys Res Commun. 2005 Sep 23;335(2):437-46. doi: 10.1016/j.bbrc.2005.07.092.

Abstract

Osteoclasts are bone resorbing cells of hematopoietic origin. The hematopoietic transcription factor PU.1 is critical for osteoclastogenesis; however, the molecular mechanisms of PU.1-regulated osteoclastogenesis have not been explored. Here, we present evidence that the receptor activator of nuclear factor kappaB (RANK) gene that has been shown to be crucial for osteoclastogenesis is a transcriptional target of PU.1. The PU.1-/- progenitor cells failed to express the RANK gene and reconstitution of PU.1 in these cells induced RANK expression. Treatment of the PU.1 reconstituted cells with M-CSF and RANKL further augmented the RANK gene expression. To explore the regulatory mechanism of the RANK gene expression by PU.1, we have cloned the human RANK promoter. Transient transfection assays have revealed that the 2.2-kb RANK promoter was functional in a monocyte line RAW264.7, whereas co-transfection of PU.1 transactivated the RANK promoter in HeLa cells. Taken together, these results suggest that PU.1 regulates the RANK gene transcription and this may represent one of the key roles of PU.1 in osteoclast differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Southern
  • Carrier Proteins / metabolism*
  • Cell Differentiation
  • Cell Line
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • DNA, Complementary / metabolism
  • Gene Expression Regulation*
  • Glycoproteins / biosynthesis*
  • HeLa Cells
  • Humans
  • Liver / embryology
  • Macrophage Colony-Stimulating Factor / metabolism
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Monocytes / metabolism
  • Mutation
  • Myeloid Progenitor Cells / cytology*
  • NF-kappa B / metabolism
  • Osteoclasts / metabolism*
  • Osteoprotegerin
  • Plasmids / metabolism
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / physiology*
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear / biosynthesis*
  • Receptors, Tumor Necrosis Factor / biosynthesis*
  • Retroviridae / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Signal Transduction
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Time Factors
  • Trans-Activators / chemistry
  • Trans-Activators / physiology*
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection

Substances

  • Carrier Proteins
  • DNA, Complementary
  • Glycoproteins
  • Membrane Glycoproteins
  • NF-kappa B
  • Osteoprotegerin
  • Proto-Oncogene Proteins
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11A protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • Tnfrsf11a protein, mouse
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Trans-Activators
  • proto-oncogene protein Spi-1
  • Macrophage Colony-Stimulating Factor