Transcription factor CREB is phosphorylated in human molar odontoblasts and cementoblasts in vivo
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SHORT COMMUNICATION
Transcription factor CREB is phosphorylated in human molar odontoblasts and cementoblasts in vivo Franz-Josef Klinz • Yu¨ksel Korkmaz Britta Cho • Wolfgang H.-M. Raab • Klaus Addicks
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Accepted: 27 October 2012 / Published online: 10 November 2012 Ó Springer-Verlag Berlin Heidelberg 2012
Abstract A wide variety of stimuli can trigger activation of the transcription factor CREB (cAMP-responsive element binding protein), pointing toward a central role for CREB in the integration of various signaling inputs. No data are available on the expression and phosphorylation of CREB in mammalian teeth. Using immunohistochemical analysis of free-floating sections, we show here that CREB was strongly expressed and phosphorylated at Ser-133 within the nucleus of a subpopulation of adult human molar odontoblasts. Many dental pulp stromal cells and periodontal ligament fibroblasts expressed CREB and showed phosphorylation of CREB at Ser-133. In addition, cementoblasts displayed nuclear expression and phosphorylation of CREB at Ser-133. The epithelial rests of Malassez revealed strong nuclear expression of CREB, but phosphorylation at Ser-133 was variable. Our results provide the first evidence that the constitutively phosphorylated transcription factor CREB is involved in the biomineralization process of adult human molar odontoblasts and cementoblasts. Keywords Biomineralization cAMP-responsive element binding protein Cementoblast Epithelial rests of Malassez Odontoblast Phospho-CREB Ser-133
F.-J. Klinz (&) K. Addicks Department of Anatomy I, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany e-mail: [email protected] Y. Korkmaz B. Cho W. H.-M. Raab Department of Operative Dentistry, Periodontics and Endodontics, Heinrich-Heine-University, Du¨sseldorf, Germany
Introduction cAMP-responsive transcription is mediated by members of the CREB/ATF family (CREB, ATF-1, CREM). CREB is nearly ubiquitously expressed in mice (Bleckmann et al. 2002) and regarded as the predominant form of the CREB/ ATF family members in many cell types. It is generally believed that signal-induced phosphorylation of CREB at Ser-133 followed by recruitment of the transcriptional coactivators CBP and p300 leads to full transcriptional activity of CREB. Overall, more than 300 different stimuli have been reported to activate CREB (for review, see Johannessen et al. 2004). Genome-wide studies indicate that functional CREB binding sites occur in about 5,000 mammalian genes (Impey et al. 2004; Zhang et al. 2005). Teeth are composed of enamel, dentin, and dental pulp. The dental pulp contains nerve fibers, blood vessels, stromal cells, and odontoblasts (for review, see Mjo¨r et al. 2001; Trowbridge 2003). In the course of tooth development, ectomesenchymal cells differentiate into odontoblasts. Odontoblasts synthesize the dentin matrix that serves as a protective barrier for the dentin–pulp complex. Depending on various stimuli and the regeneration capacity of dental pulp stromal cells, new odont
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