EMMPRIN在小鼠下颌第一磨牙形态发生及硬组织形成中的功能性作用

目的研究小鼠下颌第一磨牙中后期牙胚发育过程中细胞外基质金属蛋白酶诱导因子（EMMPRIN）的表达情况及其对牙齿细胞外基质分泌和矿化的影响。方法采用免疫组织化学方法检测EMMPRIN在牙胚发育各个阶段中的表达定位；应用体外牙胚器官培养法以及抗体阻断的方法观察EMMPRIN功能性缺失对于牙胚形态发生的影响；采用Real—TimePCR技术检测EMMPRIN相关基因的表达变化。结果EMMPRIN蛋白特异性地表达于牙胚的帽状期、钟状期以及其后的分泌期；阻断体外培养牙胚中EMMPRIN的蛋白活性可导致牙釉质形成障碍，同时下调牙胚培养物中EMMPRIN相关基因MMP-9、MMP．13、MMP．20、ALPL、ameloblastin、amelogenin和enamelinmRNA的表达。结论EMMPRIN的表达贯穿于牙胚发生发育的多个阶段；EMMPRIN可能通过调控金属基质蛋白酶和（或）相关釉质基质蛋白而在成釉细胞的分化及釉质基质的分泌、矿化过程中发挥关键作用。

Functional role of EMMPRIN in morphogenesis of tooth germ and formation of hard tissues in mouse mandibular first molars

Objective To explore expression of extracellular matrix metalloproteinase inducer （EMMPRIN） during mid- and late-stage of mouse low first molar development and its effect on secretion and mineralization of dental matrices. Methods Immunohistochemistry was used to detect EMMPRIN expression in the developing tooth germ at different stages. Tooth germ culture was performed in association with EMMPRIN inhibition assay to observe the consequence of EMMPRIN defects on the morphogenesis of tooth germ. Meanwhile, the mRNA expression of EMMPRIN-related genes was examined by Real-Time PCR. Results Specific expression of EMMPRIN was detected in the tooth germs at cap stage, bell stage, as well as secretory stage. EMMPRIN abrogation resulted in the disturbance of amelogenesis and the downregulation of MMP-9, MMP- 13, MMP-20, ALPL, ameloblastin, amelogenin, and enamelin mRNA expression in cultured tooth germ explants. Conclusion EMMPRIN was expressed in the different stages of tooth germ development. EMMPRIN played a critical role in the differentiation of ameloblast as well as the secretion and mineralization of enamel matrix, possibly by regulating the mRNA expression of MMPs and/or related enamel matrix proteins.