Although the mechanisms involved in dentinogenesis are unknown, it is clear that a unique set of extracellular matrix (ECM) proteins participates in the formation of predentin and its subsequent mineralization to form dentin. Mature odontoblasts secrete collagen at the cell border and non-collagenous proteins (NCPs) at the mineralization front (possibly through odontoblastic processes). Here NCPs form complexes with collagen. Carbonate apatite crystals are formed and this site-specific process of crystal initiation and growth is believed to be controlled by the collagen-NCP complex. In order to elucidate details of dentinogenesis, additional information relative to the NCPs, their metabolism and gene regulation is needed. Of particular interest are proteins found uniquely in dentin ECM. One dentin specific protein, dentin sialoprotein (DSP), a 53 kDa protein, is a sialic acid-rich protein similar in overall properties to cell attachment proteins bone sialoprotein (BSP) and osteopontin (OPN). However, DSP is synthesized only by odontoblasts and dental pulp and not by osteoblasts or other cell types. The sequence of DSP deduced from its cDNA is dissimilar to those of BSP, OPN and other proteins. DSP contains consensus sequences for N- and O-glycosylation sites, as well as casein kinase and 11 phosphorylation sites. Northern blots detected multiple transcripts of approximately 4.6 kb and 1.5 kb. Recent Southern blot analysis of genomic clones strongly suggests the presence of two related DSP genes. We hypothesize that the synthesis and secretion of DSP is crucial to the formation of healthy dentin. In order to test this hypothesis, we will employ molecular biological techniques to elucidate gene structures and their regulation. We propose the following Specific Aims: i. To determine the genomic organization of DSP gene(s). 2. To characterize multiple DSP transcripts and to examine the spatial and temporal expression of these transcripts. 3. To characterize the promoter(s) of DSP gene(s) including DNA sequence, minimal regulatory sequences and nuclear transcription factors and 4. To study the potential regulation of the DSP gene(s) by signal transducing molecules. The studies outlined in this proposal will provide a solid molecular basis for understanding important regulatory events controlling dentinogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
1R01DE011442-01
Application #
2132760
Study Section
Special Emphasis Panel (ZRG4-OBM-2 (06))
Project Start
1995-09-30
Project End
1996-01-31
Budget Start
1995-09-30
Budget End
1996-01-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Other Basic Sciences
Type
Schools of Dentistry
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Ritchie, Helena H; Yee, Colin T; Tang, Xu-Na et al. (2012) DSP-PP precursor protein cleavage by tolloid-related-1 protein and by bone morphogenetic protein-1. PLoS One 7:e41110
Tang, Xu-na; Zhu, Ya-qin; Marcelo, Cynthia L et al. (2011) Expression of mineralized tissue associated proteins: dentin sialoprotein and phosphophoryn in rodent hair follicles. J Dermatol Sci 64:92-8
Jiang, Long; Zhu, Ya-Qin; Du, Rong et al. (2008) The expression and role of stromal cell-derived factor-1alpha-CXCR4 axis in human dental pulp. J Endod 34:939-44
Godovikova, Valentina; Ritchie, Helena H (2007) Dynamic processing of recombinant dentin sialoprotein-phosphophoryn protein. J Biol Chem 282:31341-8
Liu, Jun; Jin, Taocong; Chang, Syweren et al. (2007) Matrix and TGF-beta-related gene expression during human dental pulp stem cell (DPSC) mineralization. In Vitro Cell Dev Biol Anim 43:120-8
Godovikova, Valentina; Li, Xiu-Rong; Saunders, Thomas L et al. (2006) A rat 8 kb dentin sialoprotein-phosphophoryn (DSP-PP) promoter directs spatial and temporal LacZ activity in mouse tissues. Dev Biol 289:507-16
Lee, Y-L; Liu, J; Clarkson, B H et al. (2006) Dentin-pulp complex responses to carious lesions. Caries Res 40:256-64
Liu, Jun; Jin, Taocong; Ritchie, Helena H et al. (2005) In vitro differentiation and mineralization of human dental pulp cells induced by dentin extract. In Vitro Cell Dev Biol Anim 41:232-8
Ritchie, H H; Park, H; Liu, J et al. (2004) Effects of dexamethasone, vitamin A and vitamin D3 on DSP-PP mRNA expression in rat tooth organ culture. Biochim Biophys Acta 1679:263-71
Ritchie, H H; Li, X R; Hanks, C T et al. (2002) The conservation and regulation of rat DSP-PP gene. Connect Tissue Res 43:331-7

Showing the most recent 10 out of 22 publications