Date of Award

2018

Document Type

Thesis - MUSC Only

Degree Name

Master of Science (MS)

Department

Stomatology

College

College of Dental Medicine

First Advisor

Yan Huang

Second Advisor

Renata S. Leite

Third Advisor

Joe W. Krayer

Abstract

Background: Periodontitis is a complex multifactorial disease that results in loss of periodontal attachment and alveolar bone. The etiologies include pathogenic bacteria and the host’s immune response. Lipopolysaccharides (LPS) are large molecules that elicit strong immune responses. They consist of a lipid and a polysaccharide composed of O-antigen and are found in the outer membrane of gram-negative bacteria. Saturated fatty acids play an important role in the development of metabolic syndrome (MetS). MetS as a pre-diabetic state is associated with increased risk of periodontitis. It has also been shown that saturated fatty acids, such as palmitic acid, enhance LPS-induced tissue inflammation. Both CD36 and GPR40 are receptors for long-chain free fatty acids. LPS induces overexpression of CD36 and GPR40. The results of this study will be utilized to further understand the pathogenesis of periodontitis and be used for development of improved treatment modalities. Objective: The objective of this study was to determine if the expression of fatty acid receptors CD36 and GPR40 is increased in periodontal tissue of patients with periodontitis and/or MetS as compared to that of periodontally healthy control patients. Materials and Methods: The study included forty-eight (48) participants divided into 4 groups. One control group, with eleven (11) participants, who did not have periodontitis or metabolic syndrome; and three test groups, which included, a periodontitis alone group, with eleven (11) participants; a MetS alone, with twelve (12) participants; and a MetS-associated periodontitis group, with fourteen (14) participants. Periodontitis was defined as an area on a tooth with probing depth greater than, or equal to, 5 mm with bleeding on probing. To be included in the metabolic syndrome group, patients must have reported elevated waist circumference of greater than 40 inches for men, and greater than 35 inches for women (obese) plus two of the following characteristics: elevated triglycerides (equal to, or greater than, 150 mg/dL), reduced HDL cholesterol, (less than 40 mg/dL for men and less than 50 mg/dL for women), elevated blood pressure (equal to, or greater than 130/85 mm Hg) or use of medication for hypertension, and/or elevated fasting glucose (> 100 mg/dL) or use of medication for hyperglycemia. Tissue samples from healthy and periodontally involved teeth were obtained. Periodontal tissue was collected from all participants and histology and immunohistochemistry were performed to determine protein expression and identify the presence of CD36 and GPR40. Results: Immunohistochemistry and conventional histological examination of the tissue samples revealed that GPR40 is highly expressed in epithelial cells, fibroblasts and infiltrated leukocytes in the periodontitis, MetS, and MetS-associated periodontitis groups compared to that of the control group. CD36 is overexpressed mainly in the MetS-associated periodontitis group. Conclusions: Conventional histologic and immunohistochemistry examination of tissues showed that the fatty-acid receptor, GPR40, is highly expressed in epithelial cells, fibroblasts and infiltrated leukocytes in periodontal tissues of all test groups when compared to healthy controls. CD36, on the other hand, was overexpressed in the MetS-associated periodontitis group only. This suggests that patients with periodontitis and metabolic syndrome may have increased uptake of saturated fatty acids through GPR40 and CD36, resulting in increased periodontal attachment loss in response to LPS and/or saturated fatty acids. This study suggests that fatty acids may play an important role in MetS-associated periodontitis by enhancing LPS-induced expression of inflammatory cytokines.

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