The long-ranged goal of these studies is to elucidate the mechanism (s) of dentin sialophosphoportein (DSPP) in dentinogenesis and thereby provide new avenues for inducing the repair and regeneration of teeth. The most abundant and important proteins in dentin are collagen type I and DSPP. Mutations of DSPP are associated with dentinogenesis imperfectas (DGI), the most common dentin genetic disorders. DSPP protein is processed by proteases into several functional fragments;DSP, DPP and others. These domains play unique biological functions during dentinogenesis. Preliminary data showed that 1). BMP2 induced DSPP expression. Teeth in BMP2 null mice are similar to DGI with DSPP mutations and expression of DSPP and Dlx3 and Osx transcriptional factors were also decreased in BMP2 knock-out mice;2). MMP-9 specially catalyzes DSP into the NH2-terminal and COOH-terminal fragments. The NH2- and COOH-terminal fragments of DSP show a clear difference in tooth distributions. Defect in teeth and interference of DSPP processing were seen in MMP-9 null mice. 3). The NH2-terminal and COOH-terminal domains bind to their receptors, integrin 26 and CD105, on cellular membrane. Based on these findings, we propose the following hypothesis that the transcriptional regulation, posttranslational modification and signal transduction of DSPP are important for controlling the initiation, rate and extent of dentin biomineralization. To test this hypothesis, we propose the following Specific Aims: 1. to determine BMP2 signaling pathways in DSPP transcription during dentinogenesis. 2. To determine processing patterns of DSP and cleaved sites of DSP by MMP-9. 3. To determine DSP signaling pathways via integrin 26 and CD105 during tooth development. This is an innovative hypothesis that each step of transcription, posttranslational processing and signaling transduction of DSP/DSPP is necessary for the formation of healthy dentin. Such knowledge will advance our understanding of the pathogenesis of inherited disorders that threaten the structural integrity of dentin and provide a potential clue for treating dental diseases.
Dentin sialophosphoprotein (DSPP) protein is important for dentin formation as DSPP mutations cause dentinogenesis imperfectas, the most common dentin genetic diseases. Here, we propose a novel pathway for DSPP transcriptional regulation, proteolytic processing and signaling transduction pathway for dentinogenesis. Thereafter, better understanding of the mechanisms of DSPP biological functions will provide new avenues for repair and regeneration of teeth.
|Wu, Li-An; Wang, Feng; Donly, Kevin J et al. (2016) Establishment of Immortalized BMP2/4 Double Knock-Out Osteoblastic Cells Is Essential for Study of Osteoblast Growth, Differentiation, and Osteogenesis. J Cell Physiol 231:1189-98|
|Chen, Zhuo; Li, Wentong; Wang, Han et al. (2016) Klf10 regulates odontoblast differentiation and mineralization via promoting expression of dentin matrix protein 1 and dentin sialophosphoprotein genes. Cell Tissue Res 363:385-98|
|Wan, Chunyan; Yuan, Guohua; Luo, Daoshu et al. (2016) The Dentin Sialoprotein (DSP) Domain Regulates Dental Mesenchymal Cell Differentiation through a Novel Surface Receptor. Sci Rep 6:29666|
|He, Y D; Sui, B D; Li, M et al. (2016) Site-specific function and regulation of Osterix in tooth root formation. Int Endod J 49:1124-1131|
|Wu, Lian; Wang, Feng; Donly, Kevin J et al. (2015) Establishment of Immortalized Mouse Bmp2 Knock-Out Dental Papilla Mesenchymal Cells Necessary for Study of Odontoblastic Differentiation and Odontogenesis. J Cell Physiol 230:2588-95|
|Guo, Feng; Feng, Junsheng; Wang, Feng et al. (2015) Bmp2 deletion causes an amelogenesis imperfecta phenotype via regulating enamel gene expression. J Cell Physiol 230:1871-82|
|Diaz de Guillory, Carolina; Schoolfield, John D; Johnson, Dorthea et al. (2014) Co-relationships between glandular salivary flow rates and dental caries. Gerodontology 31:210-9|
|Yuan, Guohua; Zhang, Li; Yang, Guobin et al. (2014) The distribution and ultrastructure of the forming blood capillaries and the effect of apoptosis on vascularization in mouse embryonic molar mesenchyme. Cell Tissue Res 356:137-45|
|Villar, C C; Lin, A L; Cao, Z et al. (2013) Anticandidal activity and biocompatibility of a rechargeable antifungal denture material. Oral Dis 19:287-95|
|Liu, Huan; Lin, Heng; Zhang, Li et al. (2013) miR-145 and miR-143 regulate odontoblast differentiation through targeting Klf4 and Osx genes in a feedback loop. J Biol Chem 288:9261-71|
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