Carbonic anhydrase II is an AP-1 target gene in osteoclasts

J Cell Physiol. 2001 Jul;188(1):89-97. doi: 10.1002/jcp.1099.

Abstract

c-Fos, a member of the AP-1 family of transcription factors, is necessary for osteoclast differentiation but to date, none of the osteoclast-phenotypic markers have been identified as AP-1 target genes. Here, we demonstrate that carbonic anhydrase II (CA II), an enzyme necessary for osteoclast activity, is transcriptionally upregulated by c-Fos/AP-1. A functional AP-1 binding site is present in the CA II promoter and is necessary for this regulation. Furthermore, we show that AP-1 binding activity, mainly composed of Fra-2 and JunD, is induced by treatment of bone marrow cultures with the osteoclastogenic hormone 1,25 dihydroxyvitamin D(3). Fra-2 and JunD are found in mature osteoclasts as well. Thus, our data demonstrate that cFos/AP-1 can directly regulate the expression of this osteoclast marker and that AP-1 activity is upregulated in osteoclast progenitors in response to osteoclastogenic signals.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Bone Marrow Cells / physiology
  • Calcitriol / pharmacology*
  • Carbonic Anhydrases / genetics
  • Carbonic Anhydrases / metabolism*
  • Cells, Cultured
  • Chickens
  • DNA-Binding Proteins / metabolism
  • Fos-Related Antigen-2
  • Humans
  • Immunohistochemistry
  • Nuclear Proteins / metabolism
  • Osteoclasts / drug effects*
  • Osteoclasts / enzymology
  • Osteoclasts / physiology*
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Proto-Oncogene Proteins c-jun / metabolism
  • Rats
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism*
  • Transcription Factors / metabolism
  • Transfection

Substances

  • DNA-Binding Proteins
  • FOSL2 protein, human
  • Fos-Related Antigen-2
  • Fosl2 protein, rat
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • Transcription Factors
  • Carbonic Anhydrases
  • Calcitriol
  • Tetradecanoylphorbol Acetate