Elevated extracellular calcium increases expression of bone morphogenetic protein-2 gene via a calcium channel and ERK pathway in human dental pulp cells
Elevated extracellular calcium increases expression of bone morphogenetic protein-2 gene via a calcium channel and ERK pathway in human dental pulp cells
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DOI：
10.1016/j.bbrc.2010.03.135
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发表时间：
2010-04-16
影响因子：
3.1
通讯作者：
Shimauchi, Hidetoshi
中科院分区：
文献类型：
--
作者：
Tada, Hiroyuki;Nemoto, Eiji;Shimauchi, Hidetoshi
牙髓细胞具有与成骨细胞相同的表型特征，能够分化为成牙本质细胞样细胞并产生牙本质样矿物结构。细胞外Ca ~（2+）升高通过刺激成骨细胞的增殖和分化参与骨生成;然而，Ca ~（2+）信号在牙生成中的作用仍不清楚。我们发现高浓度的Ca-O（2+）可增加人牙髓细胞中骨形态发生蛋白（BMP）-2基因的表达。这种增加不仅在转录水平上，而且在转录后水平上被调制，因为用Ca 2+处理增加了在存在放线菌素D（转录抑制剂）的情况下BMP-2 mRNA的稳定性。在来自口腔组织的其他人间充质细胞中观察到BMP-2 mRNA水平的类似增加;牙周韧带细胞和牙龈成纤维细胞。然而，后者的细胞表现出相当低的BMP-2 mRNA的表达与牙髓细胞和牙周膜细胞相比。细胞外信号调节激酶（ERK）抑制剂PD 98059预处理可显著抑制BMP-2的增加，L型钙通道抑制剂硝苯地平可部分抑制BMP-2的增加。然而，硝苯地平预处理对由Ca 2+触发的ERK 1/2磷酸化没有影响，这表明来自Ca 2+通道的Ca 2+内流可能独立于ERK信号转导而起作用。牙髓细胞不表达钙敏感受体（Ca 2 + sensing receptor，CaSR）的转录本，对其他阳离子如Sr 2+和精胺的反应较弱，提示牙髓细胞对Ca-o（2+）的反应方式与CaSR不同，对Ca-o（2+）的反应更为特异。(C)2010年爱思唯尔公司All rights reserved.
Dental pulp cells, which have been shown to share phenotypical features with osteoblasts, are capable of differentiating into odontoblast-like cells and generating a dentin-like mineral structure. Elevated extracellular Ca2+ Ca-o(2+) has been implicated in osteogenesis by stimulating the proliferation and differentiation of osteoblasts; however, the role of Ca-o(2+) signaling in odontogenesis remains unclear. We found that elevated Ca-o(2+) increases bone morphogenetic protein (BMP)-2 gene expression in human dental pulp cells. The increase was modulated not only at a transcriptional level but also at a post-transcriptional level, because treatment with Ca2+ increased the stability of BMP-2 mRNA in the presence of actinomycin D, an inhibitor of transcription. A similar increase in BMP-2 mRNA level was observed in other human mesenchymal cells from oral tissue; periodontal ligament cells and gingival fibroblasts. However, the latter cells exhibited considerably lower expression of BMP-2 mRNA compared with dental pulp cells and periodontal ligament cells. The BMP-2 increase was markedly inhibited by pretreatment with an extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and partially inhibited by the L-type Ca2+ channels inhibitor, nifedipine. However, pretreatment with nifedipine had no effect on ERK1/2 phosphorylation triggered by Ca2+, suggesting that the Ca2+ influx from Ca2+ channels may operate independently of ERK signaling. Dental pulp cells do not express the transcript of Ca2+-sensing receptors (CaSR) and only respond slightly to other cations such as Sr2+ and spermine, suggesting that dental pulp cells respond to Ca-o(2+) to increase BMP-2 mRNA expression in a manner different from CaSR and rather specific for Ca-o(2+) among cations. (C) 2010 Elsevier Inc. All rights reserved.