Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Department of Pediatric Dentistry, National Taiwan University School of Dentistry, Taipei City, Taiwan R.O.C.
Mol Genet Genomic Med. 2020 Aug;8(8):e1307. doi: 10.1002/mgg3.1307. Epub 2020 Jun 3.
Matrix metallopeptidase 20 (MMP20) is an evolutionarily conserved protease that is essential for processing enamel matrix proteins during dental enamel formation. MMP20 mutations cause human autosomal recessive pigmented hypomaturation-type amelogenesis imperfecta (AI2A2; OMIM #612529). MMP20 is expressed in both odontoblasts and ameloblasts, but its function during dentinogenesis is unclear.
We characterized 10 AI kindreds with MMP20 defects, characterized human third molars and/or Mmp20 mice by histology, Backscattered Scanning Electron Microscopy (bSEM), µCT, and nanohardness testing.
We identified six novel MMP20 disease-causing mutations. Four pathogenic variants were associated with exons encoding the MMP20 hemopexin-like (PEX) domain, suggesting a necessary regulatory function. Mutant human enamel hardness was softest (13% of normal) midway between the dentinoenamel junction (DEJ) and the enamel surface. bSEM and µCT analyses of the third molars revealed reduced mineral density in both enamel and dentin. Dentin close to the DEJ showed an average hardness number 62%-69% of control. Characterization of Mmp20 mouse dentin revealed a significant reduction in dentin thickness and mineral density and a transient increase in predentin thickness, indicating disturbances in dentin matrix secretion and mineralization.
These results expand the spectrum of MMP20 disease-causing mutations and provide the first evidence for MMP20 function during dentin formation.
基质金属蛋白酶 20（MMP20）是一种进化上保守的蛋白酶，对于牙釉质形成过程中釉基质蛋白的加工至关重要。MMP20 突变导致人类常染色体隐性色素减退型牙本质形成不全（AI2A2；OMIM #612529）。MMP20 在成牙本质细胞和成釉细胞中均有表达，但在牙本质形成过程中的功能尚不清楚。
我们对 10 个具有 MMP20 缺陷的 AI 家系进行了特征描述，通过组织学、背散射扫描电子显微镜（bSEM）、µCT 和纳米硬度测试对人类第三磨牙和/或 Mmp20 小鼠进行了特征描述。
我们鉴定了六个新的 MMP20 致病突变。四个致病性变异与编码 MMP20 血红素结合（PEX）结构域的外显子相关，提示其具有必要的调节功能。突变型人釉质硬度在牙本质牙釉质交界处（DEJ）和釉质表面之间最软（正常的 13%）。第三磨牙的 bSEM 和 µCT 分析显示釉质和牙本质的矿化密度均降低。靠近 DEJ 的牙本质硬度平均值为对照的 62%-69%。Mmp20 小鼠牙本质的特征分析显示牙本质厚度和矿化密度显著降低，前期牙本质厚度短暂增加，表明牙本质基质分泌和矿化受到干扰。
这些结果扩展了 MMP20 致病突变谱，并首次提供了 MMP20 在牙本质形成过程中功能的证据。
