Study of the role of the Slc11a1 gene and genotypes selected for minimum and maximum inflammatory reactivity along alveolar bone repair process in mice.

• Grant number: 13/25824-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2014
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Gustavo Pompermaier Garlet
• Grantee: Priscila Maria Colavite Machado
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

Bone is a mineralized tissue formed by different cell types and a frequently remodeled matrix; being a tissue able to be repaired by production of a new tissue with similar morphofunctional features. Little is known about the possible influences of interaction between bone and immunology systems in the bone formation and repair, as well as the molecular mechanism involved in this process remains unknown. In this context, our research group (Processes FAPESP 2010/10379-9, 2010/15755-9 e 2012/16404-0) have been studied the alveolar repair process in the mice (Vieira et al., 2013), using histomorphometric, microtomographic, besides protein analyses (ELISA) and molecular (RealTimePCR e PCRarray) methods in isogenic and knockout strains. The preliminary (Vieira et al., 2013) shown that the both inflammatory and anti-inflammatory cytokines presents important roles in the bone repair process, modulating from the influx of inflammatory cells to the mesenchymal cells recruitment (MSCs) and the osteogenesis reparative process. Interestingly, among the different strains analyzed in the preliminary study, two lineages presents a clear dichotomy in the alveolar bone repair: the AIRmax strain presents a faster and efficient repair process than the AIRmin strain, being essential to emphasize that these lineages were derived from genetics selection focused in the maximum (AIRmax) or minimum (AIRmin) inflammatory reaction. Using this mice strains is possible to study the effect of genotype/phenotype inflammatory in bone repair process, since the differential responsiveness of AIRmin and AIRmax mice is attributed to the (1) presence of the Slc11a1 gene R and/or S alleles and/or (2) the occurrence of QTLs (Quantitative Trait Loci) that by control the dichotomy of inflammatory responsiveness in AIRmin and AIRmax strains (Borrego et al., 2006; De Franco et al., 2007; Peters et al., 2007; Galvan et al., 2011). In this context, this project has the objective to characterize the role of the Slc11a1 gene (alleles R and S) and the genotypes selected for minimum and maximum inflammatory reactivity (min and max QTLs) in the alveolar bone repair process in mice. Therefore, AIRmaxRR, AIRmaxSS, AIRminRR e AIRminSS mice strains will be evaluated regarding the alveolar bone repair process after tooth extraction at 0, 3, 7 and 14 days' time points. The samples will be analyzed by means of histomorphometry (histomorphometry and picro-sirius) and µCT to determine the kinetics of bone defect repair. In a second stage the samples will be evaluated in regarding the immunologic/inflammatory profile, through the analysis of cytokines, bone metabolism and tissue repair markers by PCRarray and ELISA. Thus, the investigation of bone repair process in AIRmaxRR, AIRmaxSS, AIRminRR e AIRminSS mice strains will be generate specific knowledge the respect of role Slc11a1 gene and inflammatory QTLs contribution to the bone repair process, and also will allow us to establish a cause/effect relationship between the nature and magnitude of the inflammatory/immune process and the alveolar repair process.

Scientific publications

(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)

COLAVITE, PRISCILA MARIA; VIEIRA, ANDREIA ESPINDOLA; PALANCH REPEKE, CARLOS EDUARDO; DE ARAUJO LINHARI, RAFAELLA PAVANELLI; CARNEIRO SPERA DE ANDRADE, RAISSA GONSALVES; BORREGO, ANDREA; DE FRANCO, MARCELO; TROMBONE, ANA PAULA FAVARO; GARLET, GUSTAVO POMPERMAIER. Alveolar bone healing in mice genetically selected in the maximum (AIRmax) or minimum (AIRmin) inflammatory reaction. CYTOKINE, v. 114, p. 47-60, FEB 2019. (13/25824-6, 15/24637-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MACHADO, Priscila Maria Colavite. Role of the gene Slc11a1 and selected genotypes for minimum and maximum inflammatory reactivity in the process of alveolar bone healing in mice. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Odontologia de Bauru (FOB/SDB) Bauru.