Bartlett John D, Skobe Ziedonis, Nanci Antonio, Smith Charles E
Department of Cytokine Biology, Forsyth Institute, Cambridge, MA 02142, USA.
Eur J Oral Sci. 2011 Dec;119 Suppl 1(Suppl 1):199-205. doi: 10.1111/j.1600-0722.2011.00864.x.
Mutations of the matrix metalloproteinase 20 (MMP20, enamelysin) gene cause autosomal-recessive amelogenesis imperfecta, and Mmp20 ablated mice also have malformed dental enamel. Here we showed that Mmp20 null mouse secretory-stage ameloblasts maintain a columnar shape and are present as a single layer of cells. However, the maturation-stage ameloblasts from null mouse cover extraneous nodules of ectopic calcified material formed at the enamel surface. Remarkably, nodule formation occurs in null mouse enamel when MMP20 is normally no longer expressed. The malformed enamel in Mmp20 null teeth was loosely attached to the dentin and the entire enamel layer tended to separate from the dentin, indicative of a faulty dentino-enamel junction (DEJ). The enamel rod pattern was also altered in Mmp20 null mice. Each enamel rod is formed by a single ameloblast and is a mineralized record of the migration path of the ameloblast that formed it. The enamel rods in Mmp20 null mice were grossly malformed or absent, indicating that the ameloblasts do not migrate properly when backing away from the DEJ. Thus, MMP20 is required for ameloblast cell movement necessary to form the decussating enamel rod patterns, for the prevention of ectopic mineral formation, and to maintain a functional DEJ.
基质金属蛋白酶20(MMP20,釉质溶解素)基因突变会导致常染色体隐性遗传性釉质发育不全,敲除Mmp20基因的小鼠也有牙釉质畸形。我们在此表明,Mmp20基因敲除小鼠分泌期的成釉细胞保持柱状形态,且呈单层细胞存在。然而,该基因敲除小鼠成熟阶段的成釉细胞覆盖在牙釉质表面形成的异位钙化物质的外部结节上。值得注意的是,当MMP20通常不再表达时,基因敲除小鼠的牙釉质中会出现结节形成。Mmp20基因敲除小鼠牙齿中畸形的牙釉质与牙本质松散相连,整个牙釉质层倾向于与牙本质分离,这表明牙本质-牙釉质界(DEJ)存在缺陷。Mmp20基因敲除小鼠的釉柱模式也发生了改变。每根釉柱由单个成釉细胞形成,是形成它的成釉细胞迁移路径的矿化记录。Mmp20基因敲除小鼠的釉柱严重畸形或缺失,这表明成釉细胞在从DEJ退缩时迁移不正常。因此,MMP20对于形成交叉釉柱模式所需的成釉细胞移动、预防异位矿化以及维持功能性DEJ是必需的。