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

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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 D3. 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.