Dentin sialophosphoprotein knockout mouse teeth display widened predentin zone and develop defective dentin mineralization similar to human dentinogenesis imperfecta type III
Dentin sialophosphoprotein knockout mouse teeth display widened predentin zone and develop defective dentin mineralization similar to human dentinogenesis imperfecta type III
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DOI：
10.1074/jbc.m303908200
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发表时间：
2003-07-04
影响因子：
4.8
通讯作者：
Kulkarni, AB
中科院分区：
文献类型：
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作者：
Sreenath, T;Thyagarajan, T;Kulkarni, AB
牙本质唾液酸磷蛋白（Dspp）主要由成牙本质细胞和前成釉细胞在牙齿中表达。 Dspp mRNA 被翻译成单一蛋白质 Dspp，并裂解成两个肽，即牙本质唾液蛋白和牙本质磷蛋白，它们位于牙本质基质内。最近，在人类牙本质发育不全 II（OMIM 在线孟德尔遗传（OMIM）登录号 125490）和牙本质发育不良 II（OMIM 登录号 125420）综合征中发现了该基因的突变。在此，我们报告了 Dspp 缺失小鼠的产生，这些小鼠出现与人类牙本质发育不全 III 类似的牙齿缺陷，具有扩大的牙髓腔、增加的前牙本质区宽度、矿化不足和牙髓暴露。电子显微镜显示牙本质中存在不规则的矿化前沿，并且缺乏钙质球粒聚结。有趣的是，双糖链蛋白聚糖和核心蛋白聚糖（富含亮氨酸的小蛋白多糖）的水平在扩大的牙本质前区和空牙牙本质钙球体之间的空隙中增加。这些增强的水平与矿化缺陷区域密切相关，并进一步表明这些分子可能通过干扰钙质球粒的聚结而对牙本质矿化过程产生不利影响。总体而言，我们的结果确定了 Dspp 在协调牙本质矿化过程中必需的事件（包括蛋白多糖水平的潜在调节）中发挥着至关重要的作用。
Dentin sialophosphoprotein (Dspp) is mainly expressed in teeth by the odontoblasts and preameloblasts. The Dspp mRNA is translated into a single protein, Dspp, and cleaved into two peptides, dentin sialoprotein and dentin phosphoprotein, that are localized within the dentin matrix. Recently, mutations in this gene were identified in human dentinogenesis imperfecta II (Online Mendelian Inheritance in Man (OMIM) accession number 125490) and in dentin dysplasia II (OMIM accession number 125420) syndromes. Herein, we report the generation of Dspp-null mice that develop tooth defects similar to human dentinogenesis imperfecta III with enlarged pulp chambers, increased width of predentin zone, hypomineralization, and pulp exposure. Electron microscopy revealed an irregular mineralization front and a lack of calcospherites coalescence in the dentin. Interestingly, the levels of biglycan and decorin, small leucine-rich proteoglycans, were increased in the widened predentin zone and in void spaces among the calcospherites in the dentin of null teeth. These enhanced levels correlate well with the defective regions in mineralization and further indicate that these molecules may adversely affect the dentin mineralization process by interfering with coalescence of calcospherites. Overall, our results identify a crucial role for Dspp in orchestrating the events essential during dentin mineralization, including potential regulation of proteoglycan levels.