RANK-RANKL signaling in skeletal muscle regenaration

• Grant number: 23/14303-7
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2024
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Mariana Kiomy Osako
• Grantee: Maria Eduarda Ramos Cezine
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The interaction between bones and skeletal muscle initially referred to the mechanical interaction and anatomical proximity, however the bone-muscle unit has been updated by the description of several physiological effects mediated by soluble factors that are released by these two tissues. RANKL (receptor activator of NFkappaB ligand) and OPG (osteoprotegerin) are examples of bone-specific proteins that, together with RANK (receptor activator of NFkappaB), are essential for osteoclast activation and bone resorption, a process that involves mitochondrial biogenesis and increases the oxidative capacity of this cell. Recently, our group reported the role of the RANK-RANKL pathway in increasing oxidative metabolism through mitochondrial biogenesis in muscle fibers, as well as increased energy expenditure and resistance to fatigue in wild-type mice under RANKL treatment. Muscle regeneration is a physiological process that requires a high amount of energy to sustain tissue remodeling and the formation of new muscle fibers. Preliminary data show that the treatment with RANKL during the differentiation of myotubes derived from the C2C12 lineage leads to an increased fusion index of these cells. Therefore, in this project we evaluate the hypothesis that RANKL benefits muscle regeneration by inducing mitochondrial biogenesis and an oxidative metabolism, contributing to the stage of differentiation from the myoblast to the myotube. The results obtained in this project will contribute to the understanding of the signaling pathway activated by RANKL in muscle biology.