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Defects in the formation of the dental organ

Grant number: 04/10994-4
Support type:Research Projects - Thematic Grants
Duration: May 01, 2005 - April 30, 2010
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Sergio Roberto Peres Line
Grantee:Sergio Roberto Peres Line
Home Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
Co-Principal Investigators:Pedro Duarte Novaes


Developmental defects of tooth development are among the most common alterations of humans. Although enamel defects are not a treat to the patients' health, they may cause serious esthetical problems and interfere with masticatory and speech functions. Tooth agenesis and defects in enamel formation are among the most common alterations of human dentition. The importance of several genes in tooth development was evidenced by the lack of teeth in mutant knockout mice models and mutations in human families. Mutations in PAX9 coding sequences have been implicated in autosomal dominant oligodontia (the lack of more than 6 teeth) affecting predominantly permanent molars and second premolar. The origin of hydopontia (the lack of one to 6 teeth) is not well understood. In a previous study we have found that two polymorphisms in the promoter region of PAX9 gene are associated with hypodontia in humans (proc. FAPESP 01/08972-4, submitted for publication). These results led us to focus our analysis on the 5' region of PAX9 gene studying: (1) the association of two other polymorphisms present in this region with hypodontia; 2) study the influence of these (the 2 already identified and the two that will be investigated) polymorphisms in the transcriptional activity of PAX9 gene by the use of reporter gene systems and gel shift analysis; (3) compare the human promoter sequence with other primates from Africa (have the same number of teeth as humans) and Brazil (have 3 premolars in each hemi arc; (4) analyze the pattern of methylation in the CpG rich regions of the PAX9 promoter; (5) study the influence of vitamin A, and dexamethasone on the activity of PAX9 promoter. Enamel defects are caused by genetic or environmental factors that interfere in the formation of this tissue. These factors can interfere with the metabolism of ameloblasts or interfere directly with the formation of enamel matrix. Mutations in the amelogenin, enamelin, amelobasltin and MM-20 genes were shown to cause severe enamel malformations known as amelogenesis imperfecta in humans and mice. However, the major causes of enamel defects in human population are environmental factors. Enamel defects can be caused by fluoride, lead, biphosphonates, virus infections and high fever. Despite of many studies much remain to be known about the role of the organic matrix in the mineralization of tooth enamel as well as how genetic and environmental factors will influence the formation of this structure. The aim of the present project is: (1) study of the birrefringency of enamel matrix in the diverse phases of amelogenesis. (2) Study the effect of fluoride in the supramolecular organization of enamel matrix. (3) In collaboration with Dr. John D. Bartlett from Harvard Medical School and Dr. Ashok Kulkarni NIH-USA we intend to study the birrefringency of the enamel matrix in MMP 20 and amelogenin knockout mice (homozygous and heterozygous mice. (5) Study the effect of protease inhibitors in vitro on the birrefringency of enamel matrix. (AU)

Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RIBEIRO, MARIANA M.; DE ANDRADE, SIMONE C.; DE SOUZA, ANA PAULA; LINE, SERGIO R. P. The Role of Modularity in the Evolution of Primate Postcanine Dental Formula: Integrating Jaw Space With Patterns of Dentition. Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology, v. 296, n. 4, p. 622-629, APR 2013. Web of Science Citations: 1.
MOFATTO, LUCIANA SOUTO; FROZONI, MARCOS R. S.; DO ESPIRITO SANTO, ALEXANDRE R.; GUIMARAES, GUSTAVO NARVAES; DE SOUZA, ANA PAULA; VIDAL, BENEDICTO DE CAMPOS; PERES LINE, SERGIO ROBERTO. Fluoride effect on the secretory-stage enamel organic extracellular matrix of mice. Connective Tissue Research, v. 52, n. 3, p. 212-217, JUN 2011. Web of Science Citations: 1.
DO ESPIRITO SANTO, A. R.; MARQUES, M. R.; LINE, S. R. P. A study in situ of the effect of metallo- and serine proteinase inhibitors on the birefringence of the secretory stage enamel organic extracellular matrix. BIOTECHNIC & HISTOCHEMISTRY, v. 86, n. 2, p. 108-114, APR 2011. Web of Science Citations: 0.
RAMENZONI, LIZA L.; SAITO, CRISTIANE P. B.; JUSTIN MCCORMICK, J.; LINE, SERGIO R. P. Transcriptional activity analysis of promoter region of human PAX9 gene under dexamethasone, retinoic acid, and ergocalciferol treatment in MCF-7 and MDPC23. Cell Biochemistry and Function, v. 28, n. 7, p. 555-564, OCT 2010. Web of Science Citations: 1.
DO ESPÍRITO SANTO‚ A.R.; FROZONI‚ M.R.S.; RAMOS-PEREZ‚ F.M.M.; NOVAES‚ P.D.; LINE‚ S.R.P. Birefringence of the secretory-stage enamel organic extracellular matrix from rats submitted to successive injections of bisphosphonates. Connective Tissue Research, v. 51, n. 3, p. 208-215, 2010.
CEREDA, CÍNTIA MARIA SAIA; BRUNETTO, GIOVANA BRUSCHINI; ARAÚJO, DANIELE RIBEIRO DE; PAULA, ENEIDA DE. Liposomal formulations of prilocaine, lidocaine and mepivacaine prolong analgesic duration. Canadian Journal of Anesthesia : Journal canadien d'anesthésie, v. 53, n. 11, p. 1092-1097, Nov. 2006.
ESPÍRITO SANTO, ALEXANDRE R. DO; NOVAES, PEDRO D.; LINE, SÉRGIO R. P. Anisotropic properties of the enamel organic extracellular matrix. European Journal of Oral Sciences, v. 114, n. supl.1, p. 333-337, May 2006.

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