Activation of the Wnt/β-catenin pathway and tissue inhibitor of metalloprotease 1 during tertiary dentinogenesis.
Activation of the Wnt/β-catenin pathway and tissue inhibitor of metalloprotease 1 during tertiary dentinogenesis.
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DOI：
10.1093/jb/mvs117
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发表时间：
2013
影响因子：
2.7
通讯作者：
Seisuke Yoshioka;Yusuke Takahashi;M. Abe;Ikumi Michikami;S. Imazato;S. Wakisaka;M. Hayashi;S. Ebisu
中科院分区：
文献类型：
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作者：
Seisuke Yoshioka;Yusuke Takahashi;M. Abe;Ikumi Michikami;S. Imazato;S. Wakisaka;M. Hayashi;S. Ebisu
第三级牙本质在各种刺激后沉积在牙齿内部，是保护牙髓细胞的主要防御壁。然而，静止的成牙本质细胞、未成熟的牙髓细胞和第三级牙本质形成的分子机制仍不清楚。因此，我们对9周龄大鼠磨牙制洞后牙髓细胞的基因表达进行了全面的分析，以阐明牙本质形成过程中的关键分子。结果表明，不同分子的mRNA表达上调或下调。值得注意的是，基质金属蛋白酶家族的几个成员及其内源性抑制物在空洞准备后上调。原位杂交结果显示，金属蛋白酶组织抑制因子1(TIMP1)在活体牙髓中广泛且连续分布。用荧光免疫组织化学方法观察到β-连环蛋白在牙髓细胞中的积聚。此外，在未成熟的未分化间充质细胞中，TIMP1转录被显性负TCF4抑制，而在成熟的成牙本质细胞样细胞中，TIMP1转录没有改变。这些结果表明，窝洞预备可能激活了Wnt/β-catenin通路，而Wnt/β-catenin通路和TIMP1可能参与了牙髓修复。TIMP1可能在未成熟牙髓细胞的第三次牙本质形成中起关键作用。
Tertiary dentin is deposited inside teeth after various stimuli and serves as a major defensive wall to preserve pulp cells. However, the molecular mechanisms of the activation of quiescent odontoblasts, immature pulp cells and tertiary dentin formation are still unclear. Therefore, we performed a comprehensive gene expression analysis of pulp cells after cavity preparation of 9-week-old rat molars to clarify the critical molecules in tertiary dentinogenesis. As a result, mRNA expression of various molecules was up- or down-regulated. Notably, several members of the matrix metalloprotease family and their endogenous inhibitors were up-regulated after cavity preparation. In situ hybridization showed that tissue inhibitor of metalloprotease 1 (Timp1) was widely and continuously distributed in the pulp beneath the cavity in vivo. We also observed accumulation of β-catenin in the pulp cells beneath the cavity by fluorescence immunohistochemistry. Furthermore, Timp1 transcription was repressed by a dominant-negative TCF4 in immature undifferentiated mesenchymal cells, but not altered in mature odontoblast-like cells. These results indicate that cavity preparation may activate the Wnt/β-catenin pathway and the Wnt/β-catenin pathway and Timp1 may be correlatively involved in pulp repair. Timp1 might play crucial roles in reactivation of immature pulp cells for tertiary dentinogenesis.