This research is based on the overall hypothesis that non-collagenous extracellular matrix (ECM) proteins made by odontoblasts play a vital role in the formation of dentin. Dentin is formed when odontoblasts secrete a collagen-rich ECM that mineralizes in a highly controlled manner. Dentin ECM proteins, secreted by odontoblasts coincident with the formation of the initial predentin layer, closely resemble ECM proteins made by osteoblasts, which are implicated in osteogenesis and bone homeostasis. However, at least two of the dentin proteins are uniquely expressed by odontoblasts and not by other mineralized tissue cells. These two proteins, dentin phosphoprotein (DPP) and dentin sialoprotein (DSP), are the subjects of this application. Thus, studies are described to study the nature, cellular expression and gene structure and regulation of DPP and DSP.
The specific aims of this proposal are 1) to study the chemical nature, biosynthesis and secretion, gene structure and regulation and potential function of DPP, 2) To study mouse DSP and DSP gene sequence and organization, regulation of synthesis and potential function, and 3) To develop a null mutant DSP mouse for studying the biological function of DSP. It is expected that the results of the ongoing studies in the Principal Investigator's laboratory will bring about a better understanding of how dentin and other mineralized tissues form.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE005092-21
Application #
2733717
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1997-07-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
21
Fiscal Year
1998
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
Liang, Tian; Meng, Tian; Wang, Suzhen et al. (2016) The LPV Motif Is Essential for the Efficient Export of Secretory DMP1 From the Endoplasmic Reticulum. J Cell Physiol 231:1468-75
Gibson, Monica Prasad; Jani, Priyam; Wang, Xiaofang et al. (2014) Overexpressing the NH2-terminal fragment of dentin sialophosphoprotein (DSPP) aggravates the periodontal defects in Dspp knockout mice. J Oral Biosci 56:143-148
Gibson, Monica P; Liu, Qilin; Zhu, Qinglin et al. (2013) Role of the NH2 -terminal fragment of dentin sialophosphoprotein in dentinogenesis. Eur J Oral Sci 121:76-85
Gibson, Monica Prasad; Zhu, Qinglin; Wang, Suzhen et al. (2013) The rescue of dentin matrix protein 1 (DMP1)-deficient tooth defects by the transgenic expression of dentin sialophosphoprotein (DSPP) indicates that DSPP is a downstream effector molecule of DMP1 in dentinogenesis. J Biol Chem 288:7204-14
Gibson, Monica Prasad; Jani, Priyam; Liu, Ying et al. (2013) Failure to process dentin sialophosphoprotein into fragments leads to periodontal defects in mice. Eur J Oral Sci 121:545-50
Zurick, Kevin M; Qin, Chunlin; Bernards, Matthew T (2013) Mineralization induction effects of osteopontin, bone sialoprotein, and dentin phosphoprotein on a biomimetic collagen substrate. J Biomed Mater Res A 101:1571-81
Sun, Yao; Jiang, Yong; Liu, Qilin et al. (2013) Biomimetic engineering of nanofibrous gelatin scaffolds with noncollagenous proteins for enhanced bone regeneration. Tissue Eng Part A 19:1754-63
Gibson, M P; Zhu, Q; Liu, Q et al. (2013) Loss of dentin sialophosphoprotein leads to periodontal diseases in mice. J Periodontal Res 48:221-7
Liu, Q; Gibson, M P; Sun, Hongchen et al. (2013) Dentin sialophosphoprotein (DSPP) plays an essential role in the postnatal development and maintenance of mouse mandibular condylar cartilage. J Histochem Cytochem 61:749-58
Li, Changcheng; Xie, Xiaohua; Wang, Xiaofang et al. (2013) Differential expression and localization of dentin matrix protein 1 (DMP1) fragments in mouse submandibular glands. J Mol Histol 44:231-9

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