DFG Collaborative Research Centre 1444

Schulz and Schmidt-Bleek investigate nutrition, ageing and adipogenesis in bone maintenance and regeneration. Induction of adipogenesis, especially under pathological conditions of impaired metabolism such as ageing and obesity, or even food deprivation, indicates that fat cells in the bone marrow play a crucial role in bone maintenance and fracture repair. Dietary habits, ageing and metabolic challenges will be used to investigate whether molecular and metabolic differences in bone marrow adipocytes can be linked to efficient bone healing. Single cell analyses of adipocytes and adipogenic stem cell pools from murine and human bone material will provide insight into whether impaired metabolism and ageing can be associated with bone marrow adipocyte dysfunction and bone healing outcomes in pre-clinical studies and under clinical conditions. In pre-clinical models, positive properties of adipogenic cells on bone healing were demonstrated to arise in the context of a PPARg agonist. This positive effect could be attributed to adiponectin secreted by adipocytes, which contributes to a positive energy balance for bone formation. Under pathological conditions, however, there is excessive accumulation of fat cells in the bone marrow and the project results show that this increased formation is due to the age-related reprogramming of mesenchymal stromal cells present in the bone towards adipogenesis.