Aliskiren modulates bone metabolism in diabetic mice with periodontal disease

Author(s)

Bianca da Silva Ribeiro

• Document type: Master's Dissertation
• Press: Araçatuba. 2023-02-17.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araçatuba
• Defense date: 2022-12-21
• Advisor: Sandra Helena Penha de Oliveira

Abstract

In addition to inflammation, the renin-angiotensin system (RAS) is associated with bone remodeling through the action of angiotensin. In the present study, we evaluated the role of renin in mandibular bone metabolism in normal (N) and diabetic (D) mice with Periodontal Disease (PD). We used male Balb/c mice and diabetes was induced by peritoneal injection of streptozotocin (STZ). PD was induced by the insertion of a bilateral ligature in the lower first molars. Treatment was administered concomitantly for 15 days at a dose of 50 mg/kg of Aliskiren (Alisk). Animals were euthanized and the mandibles were collected for morphological analysis, gene expression, tissue labeling, and production of pro-inflammatory cytokines. Morphological analysis showed a marked bone loss in both groups, with worsening bone loss in group D treated with Alisk (DAlisk+PD). The production of pro-inflammatory cytokines had an increase in the expression of IL1-β in both groups with PD (NPD and DPD), an increase in the expression of IL-6 only in D mice with PD (DPD), and an increase in the TNF-α expression in N mice, but not in D mice. Treatment with Alisk significantly decreased IL-6 production in D and IL-1β mice in both groups. The gene expression of bone formation factors showed a decrease in Alp, Col1a1, and Ocn, and an increase in Bmp2 and Opn in the DPD group. Treatment with Alisk did not change Alp, Col1a1, and Ocn, but decreased Opn. In group N with PD (NPD), there was an increase in the expression of Col1a1 and Bsp. Treatment with Alisk decreased the expression of these markers (NAlisk+PD). The expression of bone resorption markers Trap, Mmp9, Oscar, and Socs1 was higher in the NPD group, while in the DPD group, there was an increase in the expression of Trap, Mmp9 Ctsk, and Oscar, and we observed the same result in the DPD group in relation to tissue labeling. Treatment in the DALisk+PD, Alisk group significantly increased the expression of Oscar and Socs1. In the NAlisk+PD group, Alisk reduced Trap and Mmp2. In conclusion, our study suggests that renin has a protective role in bone metabolism in D animals with PD since its inhibition by Alisk caused a significant deterioration in bone metabolism in these animals since in the absence of renin an increase in Oscar was observed. and SOCS-1, as well as IL-6 and IL-1β which are osteoclastogenic cytokines. (AU)

• FAPESP's process: 20/03068-9 - The role of renin-angiotensin system on bone metabolism of the mandible of diabetic mice with induced-periodontal disease
• Grantee: Bianca da Silva Ribeiro
• Support Opportunities: Scholarships in Brazil - Master