Murine matrix metalloproteinase-20 overexpression stimulates cell invasion into the enamel layer via enhanced Wnt signaling.
Murine matrix metalloproteinase-20 overexpression stimulates cell invasion into the enamel layer via enhanced Wnt signaling.
复制标题
鼠基质基质金属蛋白酶-20过表达通过增强的Wnt信号传导刺激细胞侵入牙釉质层。
DOI：
10.1038/srep29492
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发表时间：
2016-07-11
影响因子：
4.6
通讯作者：
Bartlett JD
中科院分区：
文献类型：
--
作者：
Shin M;Suzuki M;Guan X;Smith CE;Bartlett JD
基质金属蛋白酶-20（MMP-20）由发育中牙齿的成釉细胞表达，MMP-20突变导致釉质畸形。我们建立了一个稳定转染Tet-Off Mmp 20诱导的成釉细胞系，发现MMP 20表达促进细胞侵袭。以前，我们设计了驱动Mmp 20表达的转基因小鼠（Tg），并表明Mmp 20 +/+Tg小鼠具有柔软的牙釉质。在这里，我们问是否Mmp 20过表达破坏成釉细胞的功能。来自表达Mmp 20 Tg的Mmp 20 +/+小鼠的切牙具有显著的细胞浸润，其几乎取代了整个釉质层。在牙本质和牙齿外表面上仍有一薄层釉质样物质，但在这些区域之间有侵入的成纤维细胞和上皮细胞，它们包围着异位的骨样钙化。与Mmp 20消融和WT小鼠相比，Mmp 20 +/+Tg小鼠的成釉器官钙粘蛋白水平降低，并且β-连环蛋白主要存在于侵入细胞的细胞核内，而不是主要位于成釉细胞膜附近。我们的数据表明，在WT背景下转基因MMP 20增加的钙粘蛋白切割释放过量的β-连环蛋白，其易位到成釉细胞核以促进细胞迁移/侵袭。因此，我们得出结论，MMP 20通过严格控制Wnt信号在正常成釉细胞迁移中发挥作用，MMP 20过表达破坏了这一过程。
Matrix metalloproteinase-20 (MMP20) is expressed by ameloblasts in developing teeth and MMP20 mutations cause enamel malformation. We established a stably transfected Tet-Off Mmp20-inducible ameloblast-lineage cell line and found that MMP20 expression promoted cell invasion. Previously, we engineered transgenic mice (Tg) that drive Mmp20 expression and showed that Mmp20+/+Tg mice had soft enamel. Here we asked if Mmp20 overexpression disrupts ameloblast function. Incisors from Mmp20+/+ mice expressing the Mmp20 Tg had a striking cell infiltrate which nearly replaced the entire enamel layer. A thin layer of enamel-like material remained over the dentin and at the outer tooth surface, but between these regions were invading fibroblasts and epithelial cells that surrounded ectopic bone-like calcifications. Mmp20+/+Tg mice had decreased enamel organ cadherin levels compared to the Mmp20 ablated and WT mice and, instead of predominantly locating adjacent to the ameloblast cell membrane, β-catenin was predominantly present within the nuclei of invading cells. Our data suggest that increased cadherin cleavage by transgenic MMP20 in the WT background releases excess β-catenin, which translocates to ameloblast nuclei to promote cell migration/invasion. Therefore, we conclude that MMP20 plays a role in normal ameloblast migration through tightly controlled Wnt signaling and that MMP20 overexpression disrupts this process.