MMP20, KLK4, and MMP20/KLK4 double null mice define roles for matrix proteases during dental enamel formation.
MMP20, KLK4, and MMP20/KLK4 double null mice define roles for matrix proteases during dental enamel formation.
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DOI：
10.1002/mgg3.194
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发表时间：
2016-03
影响因子：
2
通讯作者：
Simmer JP
中科院分区：
文献类型：
--
作者：
Hu Y;Smith CE;Richardson AS;Bartlett JD;Hu JC;Simmer JP
基质金属蛋白酶 20 (MMP20) 和激肽释放酶相关肽酶 4 (KLK4) 是分泌型蛋白酶，对于正确的牙釉质形成至关重要。我们使用解剖和光学显微镜、背散射扫描电子显微镜 (bSEM)、SEM、微计算机断层扫描 (μCT) 和能量色散 X 射线分析 (EDX) 对野生型、Mmp20 −/−、Klk4 −/−、Mmp20 +/- Klk4 +/- 和 Mmp20 −/− Klk4 −/− 小鼠中形成的牙釉质进行了表征和比较。萌出后，在 Mmp20 −/−、Klk4 −/−、Mmp20 +/- Klk4 +/- 和 Mmp20 −/− Klk4 −/− 磨牙上观察到骨折。 Mmp20 +/- Klk4 +/- 磨牙的牙釉质失效是出乎意料的，这表明双基因效应可能导致人类牙釉质生成不全的病因学。半下颌骨的显微 CT 分析表明，相对于野生型小鼠，Mmp20 −/− 和 Klk4 −/− 小鼠的高密度牙釉质体积显着减少，而 Mmp20 −/− Klk4 −/− 小鼠的高密度牙釉质体积进一步减少。 7 周 Mmp20 −/− 和 Mmp20 −/− Klk4 −/− 下颌切牙的 bSEM 图像显示，釉质表面粗糙、有凹坑，有许多凹痕和突出的结节。 Mmp20 +/- 和 Mmp20 +/- Klk4 +/- 门牙显示出突出的、均匀间隔的水平脊，由于脊之间的山谷变暗，相对于 Mmp20 +/- 门牙，Mmp20 +/- Klk4 +/- 门牙中的脊更加明显。在横截面中，Mmp20 −/− 和 Mmp20 −/− Klk4 −/− 表现出三个不同的层。外层的元素组成受到干扰，釉质表面不规则，表面布满结节。 Mmp20 空牙釉质显然无法承受与萌发相关的巨大力量，并在发育过程中与牙本质分离。细胞侵入裂缝并插入牙本质和牙釉质层之间。 MMP20 和 KLK4 具有重叠和互补的功能，通过去除蛋白质来硬化牙釉质，但 MMP20 可能具有多种附加功能，这些功能是牙釉质粘附到牙本质、将细胞间蛋白储存释放到牙釉质基质中、成釉细胞后退以促进牙釉质层增厚以及成釉细胞及时过渡到成熟所必需的。
Matrix metalloproteinase 20 (MMP20) and kallikrein‐related peptidase 4 (KLK4) are secreted proteinases that are essential for proper dental enamel formation. We characterized and compared enamel formed in wild‐type, Mmp20 −/−, Klk4 −/−, Mmp20 +/− Klk4 +/−, and Mmp20 −/− Klk4 −/− mice using dissecting and light microscopy, backscattered scanning electron microscopy (bSEM), SEM, microcomputed tomography (μCT), and energy‐dispersive X‐ray analysis (EDX). Following eruption, fractures were observed on Mmp20 −/−, Klk4 −/−, Mmp20 +/− Klk4 +/−, and Mmp20 −/− Klk4 −/− molars. Failure of the enamel in the Mmp20 +/− Klk4 +/− molars was unexpected and suggested that digenic effects could contribute to the etiology of amelogenesis imperfecta in humans. Micro‐CT analyses of hemimandibles demonstrated significantly reduced high‐density enamel volume in the Mmp20 −/− and Klk4 −/− mice relative to the wild‐type, which was further reduced in Mmp20 −/− Klk4 −/− mice. bSEM images of 7‐week Mmp20 −/− and Mmp20 −/− Klk4 −/− mandibular incisors showed rough, pitted enamel surfaces with numerous indentations and protruding nodules. The Mmp20 +/− and Mmp20 +/− Klk4 +/− incisors showed prominent, evenly spaced, horizontal ridges that were more distinct in Mmp20 +/− Klk4 +/− incisors relative to Mmp20 +/− incisors due to the darkening of the valleys between the ridges. In cross sections, the Mmp20 −/− and Mmp20 −/− Klk4 −/− exhibited three distinct layers. The outer layer exhibited a disturbed elemental composition and an irregular enamel surface covered with nodules. The Mmp20 null enamel was apparently unable to withstand the sheer forces associated with eruption and separated from dentin during development. Cells invaded the cracks and interposed between the dentin and enamel layers. MMP20 and KLK4 serve overlapping and complementary functions to harden enamel by removing protein, but MMP20 potentially serves multiple additional functions necessary for the adherence of enamel to dentin, the release of intercellular protein stores into the enamel matrix, the retreat of ameloblasts to facilitate thickening of the enamel layer, and the timely transition of ameloblasts to maturation.