Diabetes Mellitus modify the osteogenesis signaling and compromise bone repair after rapid maxillary expansion

Author(s)

Maya Fernanda Manfrin Arnez

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Odontologia de Ribeirão Preto (PCARP/BC)
• Defense date: 2014-09-18

Examining board members

Maria Bernadete Sasso Stuani; Luciane Macedo de Menezes; Alexandra Mussolino de Queiroz; Yara Teresinha Corrêa Silva Sousa; Alexandre Elias Trivellato

• Advisor: Maria Bernadete Sasso Stuani

Abstract

Background: Diabetes mellitus (DM) is a disease associated with several disorders of health in humans and one of the most important is the jeopardizing of bone formation. However, to the best of our knowledge there is no information about the influence of diabetes on orthodontic and orthopedic treatment at cellular and molecular levels. Objective: The aim of this study was to evaluate bone remodeling process in palatal suture during orthopedic mecanotherapy in rats with type 1-induced diabetes mellitus. Material and Methods: One hundred and fifty Wistar male rats were randomly assigned to six groups. Groups: control (C, n=30), vehicle (B, n=15), type 1-induced diabetes mellitus using streptozotocin (D, n=30), control with RME (C+RME, n=30), vehicle with RME (C+RME, n=15) and type 1-induced diabetes mellitus using streptozotocin with RME (D+RME, n=30). The animals were euthanized at 3, 7 and 10 days after RME. Histologic evaluations, changes in genes and proteins expression of osteoprotegerin (OPG), RANK, RANKL, osteonectin (ONC), osteocalcin (OCC), bone sialoprotein (BSP), osteopontin (OPN) and bone morphognetic protein 2 (BMP2) were evaluated along with the changes in body weight, water intake and glycemic profile. Real-Time RT-PCR and Western Blotting were used to evaluate gene and the protein expression. Data were submitted to statistical analysis using two-way ANOVA followed by Tukey test ( α= 0,05). Results: On group D+RME it was observed an increased bone resorption, serveral undermining and tissue degradation areas. On the suture gap there were mainly inflammatory and osteoclasts cells associated with compromised bone formation compared to groups D and Cd. These results were observed also in molecular levels, since there were a reduced osteogenesis and an upregulation of osteoclastogenesis, mainly in early period of healing. On group D, bone formation was compromised compared to group C, due to changes on genes and proteins expression which regulates bone metabolism, considering that there was more immature bone and incresead active remodeling areas until late periods. On group Cd it was observed bone remodeling, characterized by desorganized tissue on the gap of midpalatal suture, with intense inflammatory hemorhagic and resorptive areas compared to group C. However until 10 days after RME, on group D the gap was not completely filled with bone tissue. These results were observed on the signaling of molecular biomarkers on group Cd, since they were changed compared to groups C and Dd. Conclusions: DM modify the signaling for bone metabolism and compromise bone repair after RME. During orthopedic and orthodontic treatment is necessary to evaluate metabolism status of subjects, since the application of these forces have been shown to promote undesirable effects mostly when associated with DM. (AU)

• FAPESP's process: 11/00166-0 - Diabetes Mellitus modify the osteogenesis signaling and compromise bone repair after rapid maxillary expansion
• Grantee: Maya Fernanda Manfrin Arnez
• Support Opportunities: Scholarships in Brazil - Doctorate