PMID- 20533306 OWN - NLM STAT- MEDLINE DCOM- 20101012 LR - 20100915 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 225 IP - 3 DP - 2010 Nov TI - Carbonic anhydrase II regulates differentiation of ameloblasts via intracellular pH-dependent JNK signaling pathway. PG - 709-19 LID - 10.1002/jcp.22267 [doi] AB - Differentiation of ameloblasts from undifferentiated epithelial cells is controlled by diverse growth factors, as well as interactions between epithelium and mesenchyme. However, there is a considerable lack of knowledge regarding the precise mechanisms that control ameloblast differentiation and enamel biomineralization. We found that the expression level of carbonic anhydrase II (CAII) is strongly up-regulated in parallel with differentiation of enamel epithelium tissues, while the enzyme activity of CA was also increased along with differentiation in ameloblast primary cultures. The expression level of amelogenin, a marker of secretory-stage ameloblasts, was enhanced by ethoxzolamide (EZA), a CA inhibitor, as well as CAII antisense (CAIIAS), whereas the expression of enamel matrix serine proteinase-1 (EMSP-1), a marker for maturation-stage ameloblasts, was suppressed by both. These agents also promoted ameloblast proliferation. In addition, inhibition of ameloblast differentiation by EZA and CAIIAS was confirmed using tooth germ organ cultures. Furthermore, EZA and CAIIAS elevated intracellular pH in ameloblasts, while experimental decreases in intracellular pH abolished the effect of CAIIAS on ameloblasts and triggered the activation of c-Jun N-terminal kinase (JNK). SP600125, a JNK inhibitor, abrogated the response of ameloblasts to an experimental decrease in intracellular pH, while the inhibition of JNK also impaired ameloblast differentiation. These results suggest a novel role for CAII during amelogenesis, that is, controlling the differentiation of ameloblasts. Regulation of intracellular pH, followed by activation of the JNK signaling pathway, may be responsible for the effects of CAII on ameloblasts. CI - (c) 2010 Wiley-Liss, Inc. FAU - Wang, Xiaogu AU - Wang X AD - Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan. FAU - Suzawa, Tetsuo AU - Suzawa T FAU - Ohtsuka, Hirotada AU - Ohtsuka H FAU - Zhao, Baohong AU - Zhao B FAU - Miyamoto, Yoichi AU - Miyamoto Y FAU - Miyauchi, Tomohiko AU - Miyauchi T FAU - Nishimura, Riko AU - Nishimura R FAU - Inoue, Tomio AU - Inoue T FAU - Nakamura, Masanori AU - Nakamura M FAU - Baba, Kazuyoshi AU - Baba K FAU - Kamijo, Ryutaro AU - Kamijo R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Amelogenin) RN - 0 (Carbonic Anhydrase Inhibitors) RN - 0 (Oligonucleotides, Antisense) RN - 0 (Protein Kinase Inhibitors) RN - 0 (RNA, Messenger) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 3.4.21.- (Kallikreins) RN - EC 3.4.21.- (kallikrein 4) RN - EC 4.2.1.- (Carbonic Anhydrase II) SB - IM MH - Ameloblasts/drug effects/*enzymology MH - Amelogenin/metabolism MH - Animals MH - Carbonic Anhydrase II/antagonists & inhibitors/genetics/*metabolism MH - Carbonic Anhydrase Inhibitors/pharmacology MH - *Cell Differentiation/drug effects MH - Cells, Cultured MH - Gene Expression Regulation, Enzymologic MH - Hydrogen-Ion Concentration MH - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism MH - Kallikreins/metabolism MH - Mice MH - Oligonucleotides, Antisense/metabolism MH - Organ Culture Techniques MH - Protein Kinase Inhibitors/pharmacology MH - RNA, Messenger/metabolism MH - *Signal Transduction/drug effects MH - Time Factors MH - Tooth Germ/cytology/drug effects/*enzymology EDAT- 2010/06/10 06:00 MHDA- 2010/10/13 06:00 CRDT- 2010/06/10 06:00 PHST- 2010/06/10 06:00 [entrez] PHST- 2010/06/10 06:00 [pubmed] PHST- 2010/10/13 06:00 [medline] AID - 10.1002/jcp.22267 [doi] PST - ppublish SO - J Cell Physiol. 2010 Nov;225(3):709-19. doi: 10.1002/jcp.22267.