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Evaluation of the synergistic effect between systemic risedronate and local genistein on peri-implant repair in estrogen deficient rats and metabolic syndrome

Grant number: 19/13954-9
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2020
Effective date (End): February 28, 2021
Field of knowledge:Health Sciences - Dentistry - Oral and Maxillofacial Surgery
Principal researcher:Roberta Okamoto
Grantee:Jaqueline Suemi Hassumi
Home Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

The aim of this project is to investigate the synergistic action of systemic risedronate sodium and locally administered genistein through the functionalization of implants, in rats submitted to ovariectomy and with feeding habits that mimicks metabolic syndrome. This project will be executed in 3 steps. In the first step, will involve the entire characterization of the surface of implants functionalized with genistein, based on chemical physical tests. In the second step biological tests will be performed on cell cultures. For the biological tests, differentiated mesenchymal cells in osteoblasts, isolated from femurs of rats will be used. Cell activity and differentiation as well as gene expression for osteogenesis will be evaluated. After the validation by the tests performed on the functionalized surfaces, will be performed the third step performed the experiments in vivo. For this purpose, young adult female Wistar rats will undergo bilateral ovariectomy and receive a hypercaloric diet, kept in sedentary conditions, mimicking the condition of metabolic syndrome. Simultaneously, young adult female Wistar rats will undergo (sham) surgery and receive a balanced diet and water ad libitum. The animals will wait 30 days to start the drug treatment with risedronate sodium at the concentration of 0.35mg / kg or only the saline solution via gavage once a week. After 30 days of the medication, all animals will undergo surgery for upper first molar extraction bilaterally. In the same time they will receive the implants in the region where the exodontia were performed. The implants will have the surfaces treated with genistein. There will be groups where the implants will not receive drugs (negative control). The euthanasia of the animals will be at 60 days after implant installation and the samples will be reserved for biomechanical (counter-torque) and real-time PCR analysis (expression of OPG, RANKL, OPN, ALP, OCN, VEGF, Wnt3a). The contra-lateral maxillae will be reserved for the analysis of calcified sections, after the administration of fluorochromes at the dose of 20 mg/kg (calcein at 14 days and alizarin at 24 days after implant installation). Initially, the samples will be evaluated by computerized microtomography for the morphometric evaluation of the bone formed around the installed implants. Later, these same samples will be submitted to the laboratory processing for calcified sections, for later analysis by confocal microscopy (peri-implant bone dynamics, BIC and AON). The quantitative data will be submitted to the homoscedasticity test to select the appropriate statistical test (parametric or non-parametric), with a significance level of 5%. (AU)

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