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 f or osteoclast differentiation but to date, none of the osteoclast-phenotypi c markers have been identified as AP-1 target genes. Here, we demonstrate t hat carbonic anhydrase II (CA II), an enzyme necessary for osteoclast activ ity, is transcriptionally upregulated by c-Fos/AP-1. A functional AP-1 bind ing site is present in the CA II promoter and is necessary for this regulat ion. Furthermore, we show that AP-1 binding activity, mainly composed of Fr a-2 and JunD, is induced by treatment of bone marrow cultures with the oste oclastogenic 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 d irectly regulate the expression of this osteoclast marker and that AP-1 act ivity is upregulated in osteoclast progenitors in response to osteoclastoge nic signals. (C) 2001 Wiley-Liss, Inc.