Effect of cannabidiol on osteoblasts, osteocytes and osteoclasts, and on bone repair

• Grant number: 24/01364-0
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Dentistry - Oral and Maxillofacial Surgery
• Principal Investigator: Emanuela Prado Ferraz
• Grantee: Emanuela Prado Ferraz
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Adalberto Luiz Rosa ; Fernando Pozzi Semeghini Guastaldi ; Márcio Mateus Beloti

Abstract

Cannabidiol (CBD) is a non-psychotropic component of Cannabis sativa and has been proven to be effective in treating conditions such as chronic pain and neurodegenerative diseases. Several studies have demonstrated that CBD's mechanism of action involves its interaction with receptors of the endocannabinoid system, which is responsible for regulating several physiological processes. Therefore, CBD may interfere with the biological activity of tissues and systems when used continuously, which needs to be investigated. Some preliminary evidence indicated that CBD interferes positively with bone repair. However, the effects of CBD, used chronically, on the differentiation of different cell types related to bone remodeling, in bone tissue, and in the repair process need to be elucidated. Based on this, the project aims to investigate whether CBD, used chronically, (1) increases or decreases the osteoblastic differentiation of mesenchymal stem cells (MSCs), osteocytes, and osteoclasts; (2) differentially affects the morphology and bone quality of the femur, calvaria, and mandibular condyle of male and female mice, (3) improves the repair of non-critical defects. For this, MSCs harvested from mouse bone marrow, osteocytes (Ocy454), and osteoclasts (RAW 264.7) will be cultured in their differentiation media with CBD and evaluated for differentiation by phenotypic methods and specific genotypic markers for each cell type. To investigate which tissue is most affected and in which gender, male and female mice will be treated daily with CBD, and the femur, calvaria, and mandibular condyle bone tissue will be subjected to microtomography, morphometric, and histology analysis. Finally, a non-critical defect will be created in the bone tissue that presents the most significant alteration from either a male or female animal, and histological, immunohistochemical, and microtomographic analyses will be performed to assess the repair. Statistical tests will be used to compare the data, depending on the distribution of the normality curve, and a significance index of 5% will be adopted. The results of the present study will contribute to understanding the cellular and molecular mechanisms involved in the effect of CBD in the context of bone biology and may guide the treatment of bone defects in patients who chronically use CBD, leading to the development of more effective therapeutic approaches. (AU)