Carbonic anhydrase II is an AP-1 target gene in osteoclasts.
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.
David
J P
JP
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
Rincon
M
M
Neff
L
L
Horne
W C
WC
Baron
R
R
D000818:Animals; D001665:Binding Sites; D001854:Bone Marrow Cells / Q000502:physiology; D002117:Calcitriol / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002645:Chickens; D004268:DNA-Binding Proteins / Q000378:metabolism; D051921:Fos-Related Antigen-2; D006801:Humans; D007150:Immunohistochemistry; D009687:Nuclear Proteins / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; C497872:FOSL2 protein, human; D051921:Fos-Related Antigen-2; C497874:Fosl2 protein, rat; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D002256:Carbonic Anhydrases; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate