IADR Abstract Archives
ERV-1 Receptor in T2 Diabetes Induced Periodontitis
Objectives: Endogenous specialized proresolving mediators derived from n-3 fatty acids known as resolvins can reverse inflammation in chronic diseases, including periodontitis and type 2 diabetes (T2D). While endogenous resolution signals are present in inflammatory diseases, the mechanism behind the failure of these signals is unknown. ERV-1, the receptor for the resolvin RvE1, is a key molecule activating resolution signals. The goal of this study is to characterize the expression and function of murine ERV-1 receptors in type 2 diabetes associated periodontitis.
Methods: Periodontitis was induced with ligature around the maxillary second molar in four strains of mice, including T2D mice (db-/-/db-/-, leptin receptor KO), transgenic mice overexpressing ERV1, a backcrossed strain of T2D ERV1 transgenic mice (db/ERV1), and wild type (WT). Periodontal disease progression at day 0, 3, 7, and 14 quantified as the rate and amount of bone loss was evaluated by histomorphometric analysis, high-resolution μCT imaging, and TRAP staining. Expression and localization of ERV-1 in situ on neutrophils and monocytes was determined by immunohistochemistry.
Results: An increase in interproximal bone loss was seen at day 3 in db-/-/db-/- compared to WT, whereas ERV1 and db/ERV1 strains were resistant to disease. There was an increase in the number of osteoclasts present over 7-14 days in db-/-/db-/- mice as indicated by TRAP staining. μCT showed that over expression of the ERV-1 receptor prevents bone loss seen in db-/-/db-/- mice. Immunohistochemical analysis revealed increased expression of ERV1 in the transgenic animals (ERV1 and db/ERV1) as expected. An upregulation of ERV1 was observed in WT after periodontitis was established.
Conclusions: The data demonstrate that overexpression of ERV1 provides a gain-of-function model for investigating the actions of RvE1. Overexpression of ERV1 in T2D mice protects from ligature induced periodontitis suggesting a major role for inflammation in the increased susceptibility to periodontitis in T2D.
Methods: Periodontitis was induced with ligature around the maxillary second molar in four strains of mice, including T2D mice (db-/-/db-/-, leptin receptor KO), transgenic mice overexpressing ERV1, a backcrossed strain of T2D ERV1 transgenic mice (db/ERV1), and wild type (WT). Periodontal disease progression at day 0, 3, 7, and 14 quantified as the rate and amount of bone loss was evaluated by histomorphometric analysis, high-resolution μCT imaging, and TRAP staining. Expression and localization of ERV-1 in situ on neutrophils and monocytes was determined by immunohistochemistry.
Results: An increase in interproximal bone loss was seen at day 3 in db-/-/db-/- compared to WT, whereas ERV1 and db/ERV1 strains were resistant to disease. There was an increase in the number of osteoclasts present over 7-14 days in db-/-/db-/- mice as indicated by TRAP staining. μCT showed that over expression of the ERV-1 receptor prevents bone loss seen in db-/-/db-/- mice. Immunohistochemical analysis revealed increased expression of ERV1 in the transgenic animals (ERV1 and db/ERV1) as expected. An upregulation of ERV1 was observed in WT after periodontitis was established.
Conclusions: The data demonstrate that overexpression of ERV1 provides a gain-of-function model for investigating the actions of RvE1. Overexpression of ERV1 in T2D mice protects from ligature induced periodontitis suggesting a major role for inflammation in the increased susceptibility to periodontitis in T2D.