Efeito da diabetes mellitus na periodontite experimental em ratos: participação da via wnt/β-catenina

Abstract

Periodontitis (PE) and diabetes mellitus (DM) represent global public health problems. Both diseases are of multifactorial etiology and evidence indicates a bidirectional relationship. The involvement of the WNT / β-catenin pathway in the bone loss processes has been highlighted, but little is known about the role of this pathway in the presence of an underlying disease, such as DM. In this context, the objective of this work was to evaluate the effect of DM on the inflammatory bone loss of rats with emphasis on the participation of the WNT / β-catenin pathway. For this purpose, 72 male Wistar rats (200-220 g) divided into 4 groups (n = 6) were used: Naïve (N), DM, PE and DM + PE. Initially, DM and DM + PE animals were submitted to type 2 DM by intraperitoneal administration of nicotinamide (230 mg / kg) followed by streptozotocin (60 mg / kg) in single doses after 08 hours of fasting. Five days after the induction of DM, the glycemic rate of the rats was measured. The PE group received saline solution (1 ml / kg-i.p). Subsequently, the PE and DM + PE groups were submitted to PE induction, which consisted of the insertion of a nylon 3.0 wire, around the upper left 2nd molar of animals under anesthesia. The DM group, under anesthesia, underwent oral manipulation without ligature insertion, whereas the animals of the Naive group received no intervention. After 11 days of PE induction all animals were euthanized. Prior to euthanasia, under blood anesthesia, blood collection was performed to perform biochemical measurements. The analyzed parameters were: 1) macroscopic analysis and micro-tomography of the bone; 2) analysis of alveolar bone evaluating inflammatory infiltrate and osteoclast and osteoblast counts; 3) Analysis of the percentage of collagen fibers of the periodontal ligament; 4) Dosing of the gingival levels of IL-8 and IL-1β; 5) Quantification of the percentage of immunoexpression of the agonist (WNT -10b) and antagonist (Dkk-1) of the WNT / β-catenin pathway; 6) Analysis of serum glucose levels, Bone Alkaline Phosphatase (BALP), calcium and phosphorus. The findings of this study showed that DM + PE increased bone loss (p <0.05) compared to the other groups. Microscopically, a greater intensity of the inflammatory infiltrate was observed in the periodontium of DM + PE (p <0.05) compared to the other groups. The DM + PE showed an increase in the gingival levels of IL-8 (p <0.05) compared to the other groups in the study. The DM + PE presented an increase of the gingival levels of IL-1β (p <0.05) compared to Naive and DM. In histomorphometry there was an increase in the number of osteoclasts and a reduction in the number of osteoblasts in DM + PE (p <0.05) compared to the other groups. It was possible to observe an increase in the percentage of immunoblotting for DKK-1 and reduction of the percentage of immunoblotting for Wnt10b in DM + PE (p <0.05) compared to the other groups. Serum levels of calcium and phosphorus showed an increase in DM + PE (p <0.05), while serum levels of BALP remained lower in this group (p <0.05) when compared to the other groups. In summary, the findings of this study showed that DM enhanced bone loss and inflammation in the periodontium of animals with PE and the WNT pathway seems to participate in this process.