Analysis of mechanisms involved in periodontal tissue destruction in obese rats with experimental periodontal disease

Author(s)

Henrique de Oliveira Bianchi

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2012-12-13

Examining board members

Dagmar Ruth Stach Machado; Cristina Pontes Vicente; Luis Carlos Spolidorio

• Advisor: Dagmar Ruth Stach Machado

Abstract

Periodontal disease (PD) is a chronic inflammatory disease that affects the tissues that support the teeth and can result in tooth loss. The etiological agent of PD is the dental plaque, which can be formed on the surface of the tooth. However, the host immune response is determinant for the susceptibility to development and progression of PD. Immune responses with a pro-inflammatory profile, represented by T helper (Th) 1 and Th17 cells, leads to PD progression, whereas an anti-inflammatory profile, represented by Th2 and T regulatory cells, is associated with no disease development. Proinflammatory cytokines induce expression of matrix metalloproteinases (MMP) and inhibit expression of their inhibitors, called tissue inhibitors of metalloproteinases (TIMP). The imbalance of MMPs/TIMPs levels is responsible for the characteristic degradation of the extracellular matrix in PD. The proinflammatory response also leads to expression imbalance of the receptor activator of nuclear factor kappa B ligand (RANKL) and its inhibitor, osteoprotegerin (OPG), resulting in alveolar bone resorption, which is the key event in tissue damage in PD. It is known that obese individuals have a higher predisposition to PD development and present a greater disease severity. Thus, the present study aimed to evaluate the influence of obesity on gene and protein changes associated with the inflammatory response and tissue destruction during the development and progression ligature-induced PD in rats. The high fat diet-induced obesity (HFD) was characterized by impaired glucose tolerance, increased blood glucose level, increased Lee index, liver alterations, increased weight of visceral fat, hyperinsulinemia and changes in plasma levels of cholesterol. Animals from HFD group showed a higher protein and gene expression of pro-inflammatory cytokines in gingival tissue affected by PD. In particular, the expression of interleukin (IL) 17, of IL6 and interferon gamma (IFNG) was significantly higher compared to the group fed a normolipidic diet. There were not much significant differences between both groups in the expression of anti-inflammatory cytokines IL4, IL10 and transforming growth factor beta (Tgfb). HFD group showed an increased MMPs gene expression, especially Mmp13, and a decrease in the expression of Timp1, Timp2 and Reversion Inducing Cysteine-rich Protein with Kazal Motifs (Reck). Moreover, we observed a significant increase in Rankl/Opg ratio in group HFD, followed by greater alveolar bone resorption. HFD induced metabolic changes that are characteristic of obesity, which resulted in exacerbation of inflammatory response in gingival tissue with PD. This pro-inflammatory response, which was polarized to Th1 and Th17 profiles, led to an imbalance in MMPs/TIMPs and Rankl/Opg gene expression ratios. Finally, the deregulation of the mediators of tissue destruction and their inhibitors resulted in worsening of PD with increased alveolar bone resorption. Therefore, this study allowed a correlation between obesity and PD progression (AU)

• FAPESP's process: 10/02558-0 - Analysis of mechanisms involved in periodontal tissue destruction on obese and obese diabetic rats with experimental periodontal disease
• Grantee: Henrique de Oliveira Bianchi
• Support Opportunities: Scholarships in Brazil - Master