Effects of social isolation, a model of depression in rats, on osteoblasts, osteoclasts and bone repair induced by mesenchymal stem cells

• Grant number: 24/10264-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2025
• End date: December 31, 2027
• Field of knowledge: Health Sciences - Dentistry - Oral and Maxillofacial Surgery
• Principal Investigator: Adalberto Luiz Rosa
• Grantee: Laís Kawamata de Jesus
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Depression is a chronic mental disorder that affects over 300 million people worldwide. During episodes of depression, people experience feelings of sadness, irritability, and emptiness, as well as a loss of interest in carrying out their activities. Depression has also been associated with reduced bone mineral density, with an increased risk of fractures. Thus, the effects of depression on osteoblasts, osteoclasts, and mainly on the interaction between these cells are of relevance as they can impair the outcomes of treatments to repair bone defects. Based on this, we hypothesized that social isolation, a model of depression in rats, negatively impacts osteoblasts, osteoclasts, their interaction and bone repair induced by cell therapy. To test this hypothesis, the effects of social isolation on osteoblast differentiation of mesenchymal stem cells (MSCs), osteoclast differentiation of monocytes, osteoblast-osteoclast interaction and bone repair induced by MSCs will be evaluated. As there are no studies comparing the effects of social isolation on bone tissue of male and female rats, such investigation will be performed and the genre that exhibits greater bone tissue alterations will be selected to conduct the further evaluations proposed in this project. Social isolation will consist of keeping 1 rat per cage and control animals will be kept 3 per cage for 10 weeks. At the end of 10 weeks, the animals will be submited to the sucrose preference and forced swim tests, and blood samples will be collected to quantify cortisol, norepinephrine and serotonin by ELISA, all parameters indicated to confirm the efficacy of this depression model. Then, the bone tissue of femurs, vertebrae and calvarias will be evaluated by microtomographic and histological analyzes. The next steps of the project will be carried out with animals of the genre in which bone tissue presents greater changes due to social isolation. MSCs and monocytes derived from the bone marrow of these animals will be cultured in osteogenic and osteoclastogenic medium, respectively, and genotypic and phenotypic markers of osteoblasts and osteoclasts will be evaluated. The interaction between osteoblasts and osteoclasts will be investigated in an indirect coculture model. MSCs will be injected into defects created in calvarias of control or socially isolated rats and the formed bone tissue will be evaluated by microtomographic and histological analyses. Our results may contribute to the development of new therapies to treat bone defects in patients with mental disorders, with applications in oral and maxillofacial surgery, implantology, periodontics and orthopedics, which would improve the quality of life of a significant part of the population