Effect of Alisquiren on alterations of RANK/RANKL/OPG axis in bone loss induced by periodontal disease in diabetic mice

• Grant number: 19/27273-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2020
• Effective date (End): December 31, 2020
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Sandra Helena Penha de Oliveira
• Grantee: Marcos Fernando Sobrinho
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Associated research grant: 15/03965-2 - Role of the renin-angiotensin system in different oral inflammatory models: an experimental interdisciplinary and clinical approach, AP.TEM

Abstract

Over the past years, possible correlations between periodontal disease (PD) and systemic diseases such as cardiovascular diseases, obesity, lung diseases and diabetes have been studied and pointed out. There is consistent evidence that severe periodontitis negatively affects glycemic control, so it is worth noting that in diabetics there is a direct relationship between periodontitis severity and diabetes complications, and vice-versa. In addition to soft tissue inflammation, PD can cause destruction of the alveolar bone (OA) by forming a network of changes in which the NF-ºB (RANKL)/Osteoprotegerin (OPG)/RANK receptor ligand system is activated, which plays an important role in the regulation of osteoclastogenesis and bone resorption. In diabetic patients the activation of this system may be more exacerbated leading to greater bone loss. The Renin-Angiotensin System (RAS) has a minor influence on the OPG/RANKL/RANK axis, as angiotensin II exerts an increase in RANKL and osteoclast activity, decreased bone deposition, osteoblast maturation, and osteocalcin (involved mineralization), ALP (alkaline phosphatase) and collagen. However, very little is known about this interaction. Thus, the aim of the present study is to evaluate the effect of renin role on OPG/RANKL/RANK axis alterations in PD-induced alveolar bone in diabetic mice, since renin is an enzyme involved in angiotensin formation. Diabetic mice with PD induced by 1st molar ligation will be used and we will evaluate the effect of aliskiren, renin inhibitor, on alveolar bone loss by histomorphometry, the expression of OPG/RANKL/RANK in OA by immunohistochemistry; OPG/RANKL/RANK expression in OA by real time RT-PCR; and the count of TRAP-positive osteoclasts in the alveolar bone by immunohistochemistry.