Regulatory potential of the type 2 cannabinoid receptor in bone remodeling in an experimental orthodontic model in osteoporotic rats

• Grant number: 25/05156-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2025
• End date: March 31, 2027
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Joni Augusto Cirelli
• Grantee: Isabela Mendes Pazello
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

The endocannabinoid system (EC) of cell signaling regulates bone homeostasis, and activation of its CB2 receptor has been associated with the inhibition of bone resorption and increased bone formation, making it a potential therapeutic target for osteoporosis and other osteometabolic diseases. These sistemic diseases affect the orthodontic tooth movement (OTM). Thus, the aim of the present study is to evaluate the effects of the EC, specifically its CB2 receptor, on the bone remodeling process in rats with osteoporosis induced by ovariectomy (OVX) subjected to OTM. For this purpose, an ex vivo phase of the study will investigate the expression of the CB2 receptor at the transcriptional level (RT-qPCR) and protein level (via immunohistochemistry) in the periodontal tissues of molars from healthy or osteoporotic rats subjected to OTM (previous study supported by FAPESP). After confirming the involvement of the CB2 receptor, the in vivo phase will assess the role of selective CB2 activation in bone remodeling through the administration of the selective agonist HU-308. For this, 24 rats will be divided into 03 experimental groups (n=8/group): OTM Group, OVX + OTM Group, and OVX + OTM + HU-308 Group. After the animals are sacrificed, alveolar bone remodeling will be measured through micro-computed tomography, histological and histomorphometric analyses. The expression of genes and proteins related to osteogenesis, osteoclastogenesis, and inflammation will be respectively evaluated through RT-qPCR and immunohistochemistry. The collected data will be tabulated, and a significance level of 5% will be adopted to determine the validity of the tested hypothesis. (AU)