Understanding the organization and functional expression of dental structural genes during human development may be helpful in formulating new diagnostic and therapeutic approaches for a number of oral diseases affecting enamel, dentine, cementum and related dental tissues. Our research program represents an interdisciplinary and multidisciplinary approach to the investigation of enamel, dentine and cementum structural genes and their products during mouse and human development. Our efforts are integrated towards understanding the molecular genetics of amelogenesis, dentinogenesis and cementogenesis. We propose to identify and characterize the structural organization of the major genes and their products associated with enamel, dentine and cementum formation in normal as well as within affected individuals expressing inherited disorders of enamel, dentine and cementum. Our experimental strategy is to identify and characterize unique proteins characteristic of enamel, dentine and cementum, and to use these polypeptides as immunogens to produce monospecific polyclonal antibodies. These antibodies are then used to identify putative antigenic cross-reactivity between mouse and human dental proteins. These antibodies are also used to characterize specific mRNAs for each of the dental non-collagenous extracellular matrix structural gene products, which are then used to produce complementary DNA probes (cDNA). Recombinant DNA techniques are employed in studies designed to determine putative homology between mice and human genomic DNA containing structural genes of enamelins, amelogenins, dentine phosphoprotein and intermediate cementum non-collagenous protein. We propose to investigate families consisting of normal and affected individuals clinically diagnosed as having one of the dental genetic diseases such as amelogenesis imperfecta (AI) or dentinogenesis imperfecta (DI). These studies will result in a detailed analysis of each of these human dental structural genes and may establish the molecular pathology for a number of inherited disorders of dental tissues.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Program Projects (P01)
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University of Southern California
Schools of Dentistry/Oral Hygn
Los Angeles
United States
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Fong, Hanson; White, Shane N; Paine, Michael L et al. (2003) Enamel structure properties controlled by engineered proteins in transgenic mice. J Bone Miner Res 18:2052-9
Moradian-Oldak, J (2001) Amelogenins: assembly, processing and control of crystal morphology. Matrix Biol 20:293-305
Wen, H B; Fincham, A G; Moradian-Oldak, J (2001) Progressive accretion of amelogenin molecules during nanospheres assembly revealed by atomic force microscopy. Matrix Biol 20:387-95
Paine, M L; White, S N; Luo, W et al. (2001) Regulated gene expression dictates enamel structure and tooth function. Matrix Biol 20:273-92
Wen, H B; Moradian-Oldak, J; Fincham, A G (2000) Dose-dependent modulation of octacalcium phosphate crystal habit by amelogenins. J Dent Res 79:1902-6
Wen, H B; Moradian-Oldak, J; Zhong, J P et al. (2000) Effects of amelogenin on the transforming surface microstructures of Bioglass in a calcifying solution. J Biomed Mater Res 52:762-73
Moradian-Oldak, J; Paine, M L; Lei, Y P et al. (2000) Self-assembly properties of recombinant engineered amelogenin proteins analyzed by dynamic light scattering and atomic force microscopy. J Struct Biol 131:27-37
Wen, H B; Moradian-Oldak, J; Leung, W et al. (1999) Microstructures of an amelogenin gel matrix. J Struct Biol 126:42-51
Fincham, A G; Moradian-Oldak, J; Simmer, J P (1999) The structural biology of the developing dental enamel matrix. J Struct Biol 126:270-99
Wen, H B; Moradian-Oldak, J; Fincham, A G (1999) Modulation of apatite crystal growth on Bioglass by recombinant amelogenin. Biomaterials 20:1717-25

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