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Modulation of Monocytic Myeloid-Derived Suppressor Cells by Cannabinoid Receptor Type 2: Implications for Osteoclastogenesis and Immunosuppression

Grant number: 25/04883-1
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Start date: September 01, 2025
End date: August 31, 2026
Field of knowledge:Health Sciences - Dentistry - Periodontology
Principal Investigator:Joni Augusto Cirelli
Grantee:Lélio Fernando Ferreira Soares
Supervisor: Keith Lough Kirkwood
Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Institution abroad: State University of New York, Buffalo State (SUNY), United States  
Associated to the scholarship:23/06881-0 - Evaluation of the anti-inflammatory and pro-osteogenic effect of OGP (10-14) in a model of induced periodontal disease: in vitro and in vivo study, BP.DR

Abstract

Monocytic myeloid-derived suppressor cells (M-MDSCs) play a crucial role in the immunopathology of periodontitis, contributing to inflammatory bone loss through immune suppression and osteoclast-mediated resorption. Similarly, the cannabinoid receptor type 2 (CB2) activation has been shown to modulate immune responses and bone remodeling, suggesting a potential role in periodontitis. However, no study to date has investigated whether CB2 receptor activation can regulate M-MDSC expansion, immune function, and differentiation into osteoclasts, thereby influencing periodontitis initiation and progression. This research aims to determine whether CB2 activation modulates M-MDSC function and osteoclastogenesis while evaluating the osteogenic growth peptide (10-14) [OGP(10-14)] as a potential therapeutic modulator of CB2 activity. Evaluations will be conducted using in vitro and ex vivo models to assess immune cell function, key marker expression, and bone remodeling outcomes. It is hypothesized that CB2 activation will suppress M-MDSC expansion and osteoclast differentiation, thereby mitigating inflammatory bone loss. In the future, this research could contribute to the development of targeted therapies for periodontitis by modulating CB2 signaling and M-MDSC activity, ultimately advancing new strategies for managing inflammatory bone diseases.

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