Understand and shape bone regeneration by cellular metabolic adaptation in immune and stromal cells (P13)

• Subject Area: Medical Informatics and Medical Bioinformatics
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 427826188

After fracture, cells need to cope with a sudden change in nutrient and oxygen supply. Consequently, local mesenchymal cells as well as local and recruited immune cells must quickly undergo metabolic reprogramming to orchestrate bone regeneration. In the first funding period, we could identify specific differences in metabolic profiles in fast and delayed healing. A key player in the coordinated inflammatory response and successful healing seems to be the central carbon metabolism. We observed a fast increase in the expression of pro-inflammatory / glycolytic pathways, followed by osteoclast differentiation adjacent to the bone cortex. In parallel and in the bone marrow cavity, changes in monocytes seemed to be closely linked to T cell responses associated with healing kinetics. For the second funding period, we hypothesize that a spatiotemporal analysis of molecular and metabolic immune as well as stromal cells reprogramming will allow us to identify site-specific communication pathways driving successful bone healing (and the lack thereof in delayed), which can serve as targets to improve challenged healing settings.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1444: Directed Cellular Self-Organization to Advance Bone Regeneration
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Heads: Professor Dr.-Ing. Georg Duda; Professorin Dr. Birgit Sawitzki