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Role of resveratrol in controlling bone changes associated with osteoporosis: study in ovariectomized rats

Grant number: 15/24458-1
Support type:Regular Research Grants
Duration: August 01, 2016 - July 31, 2018
Field of knowledge:Health Sciences - Dentistry - Periodontology
Principal Investigator:Suzana Peres Pimentel
Grantee:Suzana Peres Pimentel
Home Institution: Instituto de Ciências da Saúde (ICS). Universidade Paulista (UNIP). São Paulo , SP, Brazil
Assoc. researchers:Fabiano Ribeiro Cirano ; Fernanda Vieira Ribeiro ; Márcio Zaffalon Casati ; Renato Corrêa Viana Casarin

Abstract

Resveratrol (RESV) is a compound of important biological effects acting in the modulation of inflammatory mediators in the cascade of events related to bone metabolism. However, there is no evidence on the impact of resv in bone repair and experimental periodontitis front the presence of osteoporosis or osteonecrosis (ONM). Thus, this study aims to: 1- To evaluate the influence of the systemic use of resveratrol in the repair of bone around titanium implants placed in tibia on ovariectomized rats by (a) computerized digital microtomography (Micro-Ct), (b) reverse torque analysis of implants for removing, (c) evaluation of bone healing by gene expression, determined by quantitative PCR and histology; 2-Determining the role of resveratrol in the modulation of bone loss during experimental periodontitis in ovariectomized animals by (a) morphometric analysis, (b) immunological and oxidative stress markers tissue concentration, (c) the analysis of gene expression, by qPCR, of molecules related to bone and/or oxidative stress on tissue resorption. 3-evaluate the influence of the systemic use of resveratrol in the incidence and severity of osteonecrosis of jaws in ovariectomized rats by (a) microtomography (micro-CT), (b) evaluating the gene expression, by qPCR, of molecules related to necrosis and bone repair, (c) and histological analysis, through the evaluation of tissue immunostaining and apoptosis of bone resorption mediators. Thus, rats will be distributed in the following groups: (1) OVT + RESV (n = 10): ovariectomized animals will receive treatment with resveratrol solution, (2) OVT + PLA (n = 10): negative control - ovariectomized animals will receive treatment with placebo solution (3) OVT + ZLD+PLA (n = 10): positive control - ovariectomized animals will receive treatment with zoledronate (4) OVT + RESV + ZLD (n = 10): the ovariectomized animals will receive treatment with resveratrol and zoledronate solution, (5) SHAM (n: 10): non-ovariectomized animals receive placebo treatment solution. Ovariectomy / sham will be held on day -84. On day -42 groups who will receive the zoledronate administration will begin the treatment. On day 0 will be done the induction of ONJ and placement of implants on the left tibia. On day 28, induction of experimental periodontitis will be made and placement of implants in the right tibia; and day 56, euthanasia will be made. The treatments (according to the group) will begin on day -84 and will go untill the end of the experiment. After euthanasia, one of the implants will be submitted to CT evaluation through Micro-Ct and the other will be accessed to reverse torque analysis and evaluation of gene expression of bone markers (BMP-2, OPN, OPG, RANKL, Runx2, Osx, ²-catenin and LRP-5) in the peri-implant tissue by means of Real-time PCR. The jaws on the right will be removed for morphometric analysis and the surrounding gingival tissues will be collected for enzyme immunoassay analysis of pro and anti-inflammatory and/or to oxidative stress related markers (OPG, RANKL, Runx2, Sost and SIRT1) by Luminex/Magpix assay and ELISA. On the left side, the surrounding gingival tissues will be collected for analysis of gene expression, while the jaw will be sent to microtomography analysis to evaluate the alveolar bone loss. Osteonecrosis bone loss will be confirmed and determined on the severity of clinical parameters, microtomographic (microCT), histological and differentially expressed genes (DXX5, CTX, TRACP5b, TNF-±, OPG, RANKL, ²-catenin, SOD, GSH and GAPDH). Data will be statistically analyzed according to the degree of normality (or ANOVA Kruskal Wallis test), 5% significance level. (AU)