Carbonic Anhydrase II Regulates Differentiation of Ameloblasts via Intracellular pH-Dependent JNK Signaling Pathway
Carbonic Anhydrase II Regulates Differentiation of Ameloblasts via Intracellular pH-Dependent JNK Signaling Pathway
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DOI：
10.1002/jcp.22267
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发表时间：
2010-12-01
影响因子：
5.6
通讯作者：
Kamijo, Ryutaro
中科院分区：
文献类型：
--
作者：
Wang, Xiaogu;Suzawa, Tetsuo;Kamijo, Ryutaro
成釉细胞与未分化上皮细胞的分化受到多种生长因子以及上皮和间充质之间相互作用的控制。然而，人们对控制成釉细胞分化和牙釉质生物矿化的精确机制知之甚少。我们发现碳酸酐酶II（CAII）的表达水平与牙釉质上皮组织的分化同时强烈上调，而CA的酶活性也随着成釉细胞原代培养物的分化而增加。 CA 抑制剂乙氧唑胺 (EZA) 和 CAII 反义 (CAIIAS) 增强了釉原蛋白（分泌期成釉细胞标志物）的表达水平，而牙釉质基质丝氨酸蛋白酶-1 (EMSP-1)（成熟期成釉细胞标志物）的表达则被两者抑制。这些药物还促进成釉细胞增殖。此外，使用牙胚器官培养物证实了 EZA 和 CAIIAS 对成釉细胞分化的抑制。此外，EZA 和 CAIIAS 升高了成釉细胞的细胞内 pH 值，而实验性的细胞内 pH 值降低消除了 CAIIAS 对成釉细胞的影响，并触发了 c-Jun N 末端激酶 (JNK) 的激活。 SP600125 是一种 JNK 抑制剂，可消除成釉细胞对实验性细胞内 pH 值降低的反应，同时抑制 JNK 也会损害成釉细胞分化。这些结果表明 CAII 在成釉细胞形成过程中的新作用，即控制成釉细胞的分化。细胞内 pH 值的调节以及 JNK 信号通路的激活可能是 CAII 对成釉细胞的影响的原因。 J.细胞。生理学。 225: 709-719, 2010。(C) 2010 Wiley-Liss, Inc.
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. J. Cell. Physiol. 225: 709-719, 2010. (C) 2010 Wiley-Liss, Inc.