MMP20（Matrixmetalloproteinase-20）对于牙釉质正常发育至关重要，其缺失导致人类非综合症性牙釉质发育不全。研究显示MMP20能切割E-和N-钙粘蛋白的细胞外域，这两种钙粘蛋白在Mmp20基因敲除小鼠中表达水平显著升高。E-钙粘蛋白表达在分泌阶段下调，而N-钙粘蛋白水平上调。这种E-到N-钙粘蛋白的转换可能促进上皮细胞迁移，对牙釉质细胞排成行并滑动相互擦过的过程至关重要。
Guan, X.
Bartlett, J. D.
Matrix metalloproteinase-20 (enamelysin, MMP20) is essential for dental enamel development. Seven different MMP20 mutations in humans cause non-syndromic enamel malformations, termed amelogenesis imperfecta, and ablation of Mmp20 in mice results in thin brittle enamel with a dysplastic rod pattern. Healthy enamel formation requires the sliding movement of ameloblasts in rows during the secretory stage of development. This is essential for formation of the characteristic decussating enamel rod pattern observed in rodents, and this is also when MMP20 is secreted into the enamel matrix. Therefore, we propose that MMP20 facilitates ameloblast movement by cleaving ameloblast cell-cell contacts. Here we show that MMP20 cleaves the extracellular domains of the E- and N-cadherin adherens junction proteins, that both E- and N-cadherin transcripts are expressed at significantly higher levels in Mmp20 null vs. wild-type (WT) mice, and that in Mmp20 ablated mice, high-level ameloblast N-cadherin expression persists during the maturation stage of development. Furthermore, we show that E-cadherin gene expression is down-regulated from the pre-secretory to the secretory stage, while N-cadherin levels are up-regulated. This E- to N-cadherin switch supports epithelial migration in other tissues and may be an important event necessary for the ameloblasts to start moving in rows that slide by one another.
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