Dentin Sialoprotein is a Novel Substrate of Matrix Metalloproteinase 9 in vitro and in vivo.
Dentin Sialoprotein is a Novel Substrate of Matrix Metalloproteinase 9 in vitro and in vivo.
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DOI：
10.1038/srep42449
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发表时间：
2017-02-14
影响因子：
4.6
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Yuan G;Chen L;Feng J;Yang G;Ni Q;Xu X;Wan C;Lindsey M;Donly KJ;MacDougall M;Chen Z;Chen S
牙本质涎蛋白（DSP）是牙本质形成所必需的，在成牙本质细胞样细胞和牙室内被加工成碎片。基质金属蛋白酶9（MMP 9）在胚胎早期至成年期的牙齿中均有表达。虽然MMP 9已被报道通过加工底物参与一些生理和病理条件，但其在牙齿发育中的作用以及DSP是否是MMP 9的底物仍不清楚。本研究通过观察Mmp 9基因敲除（Mmp 9 −/−）小鼠的表型来研究MMP 9在牙齿发育中的功能，并通过体外和体内实验来探讨DSP是否是MMP 9的底物。结果显示，Mmp 9 −/−牙齿表现出类似于牙本质发生障碍的表型，包括牙本质密度降低、牙本质结构异常、前牙本质增宽和前牙本质-牙本质边界不规则。MMP 9和DSP在成牙本质细胞、前牙本质和矿化牙本质中的分布重叠，MMP 9能够与DSP特异性结合。MMP 9在体外能高效地将DSP切割成不同的片段，而MMP 9的缺失会导致DSP在天然牙齿中的不适当加工。因此，我们的研究结果表明，MMP 9是重要的牙齿发育和DSP是一个新的目标MMP 9在牙本质形成。
Dentin sialoprotein (DSP) is essential for dentinogenesis and processed into fragments in the odontoblast-like cells and the tooth compartments. Matrix metalloproteinase 9 (MMP9) is expressed in teeth from early embryonic to adult stage. Although MMP9 has been reported to be involved in some physiological and pathological conditions through processing substrates, its role in tooth development and whether DSP is a substrate of MMP9 remain unknown. In this study, the function of MMP9 in the tooth development was examined by observation of Mmp9 knockout (Mmp9−/−) mouse phenotype, and whether DSP is a substrate of MMP9 was explored by in vitro and in vivo experiments. The results showed that Mmp9−/− teeth displayed a phenotype similar to dentinogenesis imperfecta, including decreased dentin mineral density, abnormal dentin architecture, widened predentin and irregular predentin-dentin boundary. The distribution of MMP9 and DSP overlapped in the odontoblasts, the predentin, and the mineralized dentin, and MMP9 was able to specifically bind to DSP. MMP9 highly efficiently cleaved DSP into distinct fragments in vitro, and the deletion of Mmp9 caused improper processing of DSP in natural teeth. Therefore, our findings demonstrate that MMP9 is important for tooth development and DSP is a novel target of MMP9 during dentinogenesis.