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Alveolar bone repair post tooth extraction of 129/SV- WT and 129/Sv 5LOKO elderly female mice treated with high-potency bisphosphonate

Grant number: 18/19409-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2019
Effective date (End): February 29, 2020
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Mariza Akemi Matsumoto
Grantee:Isabela do Carmo Custódio
Home Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

The chronicle use of nitrogen containing bisphosphonates (nBP) for the treatment of bone metabolism diseases and disorders, such osteoporosis, is a therapeutic treatment well established, mainly involving patients at age over to 60 years old. However, this treatment is also related to the development of Osteonecrosis of Jaw (ONJ), and the risk of ONJ occurrence increase after surgical and invasive treatments, such as dental extractions. Despite ONJ has been well recognized, the cellular and inflammatory mechanisms involving its pathogenesis remain poorly understood, mainly considering the role of nPBs on the immunological system components. Then, this study aims to analyze the influence of zoledronic acid administration on the bone repair post tooth extraction in 129-SV WT mice in comparison to mice with genetic disruption for the enzyme 5-lypoxigenase (129-SV 5LOKO), which has a osteopetrotic phenotype. Thus, 20 female mice 129/Sv WT and 20 mice 5LOKO, at the age of 64 weeks, will be submitted to the right upper incisor extraction and euthansied after 7 and 21 days post surgery to samples collection. Animal will be divided into two groups: Control (treated with saline solution, at 0,9%) and ZL (intraperitoneal injection [II] of 0,1mL of Zoledronic Acid [ZA] at the dosage of 250ug/Kg) starting the treatment at 4 weeks before the surgeries and continuing until the end of experimental periods (7 and 21 days). After the euthanasia, 5 specimens of each group and experimental period will be fixed in 10% formalin formalina and submitted to the microCT scanning, then submitted to histological processing for performing histolofical sections. The microCT scannings will be processed and analyzed for qualitative (tridimensional) and quantitative evaluations from bone inside of alveolar sockets after tooth extraction. The histological slices will be stainged with hematoxilin and eosin (H&E), as well anlyzed for immunolabeling of macrophages (F480+ cells), osteoblasts (Runx2+ cells) and osteoclasts (TRAP+ cells). After quantitative data acquisition, suitable statistical tests will be applied with significance level of 5%.

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)
BIGUETTI, CLAUDIA CRISTINA; DE OLIVA, ANDRE PRIME HERGESEL; HEALY, KENT; MAHMOUD, RAMEZ HASSAN; CUSTODIO, ISABELA DO CARMO; CONSTANTINO, DULCE HELENA; ERVOLINO, EDILSON; HUNGARO DUARTE, MARCO ANTONIO; FAKHOURI, WALID D.; MATSUMOTO, MARIZA AKEMI. Medication-related osteonecrosis of the jaws after tooth extraction in senescent female mice treated with zoledronic acid: Microtomographic, histological and immunohistochemical characterization. PLoS One, v. 14, n. 6 JUN 14 2019. Web of Science Citations: 0.

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