Suzuki Shigeki, Sreenath Taduru, Haruyama Naoto, Honeycutt Cherlita, Terse Anita, Cho Andrew, Kohler Thomas, Müller Ralph, Goldberg Michel, Kulkarni Ashok B
Functional Genomics Section, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health/DHHS, 30 Convent Drive, Bethesda, MD 20892, USA.
Matrix Biol. 2009 May;28(4):221-9. doi: 10.1016/j.matbio.2009.03.006. Epub 2009 Apr 5.
Dentin sialophosphoprotein (DSPP), a major non-collagenous matrix protein of odontoblasts, is proteolytically cleaved into dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Our previous studies revealed that DSPP null mice display a phenotype similar to human autosomal dominant dentinogenesis imperfecta, in which teeth have widened predentin and irregular dentin mineralization resulting in sporadic unmineralized areas in dentin and frequent pulp exposure. Earlier in vitro studies suggested that DPP, but not DSP, plays a significant role in initiation and maturation of dentin mineralization. However, the precise in vivo roles of DSP and DPP are far from clear. Here we report the generation of DPPcKO mice, in which only DSP is expressed in a DSPP null background, resulting in a conditional DPP knockout. DPPcKO teeth show a partial rescue of the DSPP null phenotype with the restored predentin width, an absence of irregular unmineralized areas in dentin, and less frequent pulp exposure. Micro-computed tomography (micro-CT) analysis of DPPcKO molars further confirmed this partial rescue with a significant recovery in the dentin volume, but not in the dentin mineral density. These results indicate distinct roles of DSP and DPP in dentin mineralization, with DSP regulating initiation of dentin mineralization, and DPP being involved in the maturation of mineralized dentin.
牙本质涎磷蛋白（DSPP）是成牙本质细胞的一种主要非胶原蛋白基质蛋白，可被蛋白水解切割为牙本质涎蛋白（DSP）和牙本质磷蛋白（DPP）。我们之前的研究表明，DSPP基因敲除小鼠表现出与人类常染色体显性牙本质发育不全相似的表型，即牙齿的前期牙本质增宽，牙本质矿化不规则，导致牙本质中出现散在的未矿化区域，并频繁出现牙髓暴露。早期的体外研究表明，在牙本质矿化的起始和成熟过程中，起重要作用的是DPP而非DSP。然而，DSP和DPP在体内的确切作用仍远未明确。在此，我们报告了DPPcKO小鼠的产生，在DSPP基因敲除背景下，只有DSP表达，从而实现了条件性DPP基因敲除。DPPcKO小鼠的牙齿表现出DSPP基因敲除表型的部分挽救，前期牙本质宽度恢复，牙本质中没有不规则的未矿化区域，牙髓暴露也较少。对DPPcKO磨牙进行的显微计算机断层扫描（micro-CT）分析进一步证实了这种部分挽救，牙本质体积显著恢复，但牙本质矿物质密度未恢复。这些结果表明DSP和DPP在牙本质矿化中具有不同作用，DSP调节牙本质矿化的起始，而DPP参与矿化牙本质的成熟。
