
DFG Collaborative Research Centre 1444
This Collaborative Research Centre aims to unravel the basic mechanisms that differentiate between success and failure in regeneration of musculoskeletal tissue using bone healing as a role model.
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Subproject 12 - Principal Investgators
CRC 1444 Representative of all non‐university partner institutions, Subproject 12 | RU 2165 Subproject 6

CRC 1444 Deputy Scientific Coordinator & Implementation of 3R principles, Subprojects 1 & 12 | RU 2165 Subprojects 5 & 6

Bone marrow adipose tissue: Nutrient metabolism and immunomodulation during bone maintenance and regeneration

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.
Adiponectin enhances healing
Inflammatory Response | Energy Supply & Consumption
In bone regeneration, the signalling molecule adiponectin expressed by adipocytes located directly adjacent to the fracture gap enhance the healing outcome by providing energy for the anabolic bone formation process.
In collaboration with subproject P01

Age-related marrow fat accumulation
Inflammatory Response | Energy Supply & Consumption
In bone regeneration, the signalling molecule adiponectin expressed by adipocytes located directly adjacent to the fracture gap enhance the healing outcome by providing energy for the anabolic bone formation process.
In collaboration with subproject P14 and the central service project C01
Team
The benefits of adipocyte metabolism in bone regeneration

Computational Analysis of the Effects of Ageing and Diet on Stem Cell Function and Ectopic Fat Accumulation in the Musculoskeletal System

Impact of nutrient regulation on bone-resident progenitor cells, bone marrow adipogenesis and bone health

Biochemical and functional characterisation of bone regenerative marrow adipose tissue

Publications
- Authors:Burkhardt, L. M.; Bucher, C. H.; Loffler, J.; Rinne, C.; Duda, G. N.; Geissler, S.; Schulz, T. J.; Schmidt-Bleek, K.
Journal:Front Cell Dev Biol. Year:2023; Volume:11:Pages:1104709.
Title:The benefits of adipocyte metabolism in bone health and regeneration - Authors:Haueise, T.; Stefan, N.; Schulz, T. J.; Schick, F.; Birkenfeld, A. L.; Machann, J.
Journal:Z Med Phys Year:2023;
Title:Automated shape-independent assessment of the spatial distribution of proton density fat fraction in vertebral bone marrow