Zusammenstellung von Bildern aus dem Sonderforschungsbereich

C02: Osteoblast differentiation-stage specific mechanisms of glucocorticoid action during fracture healing

PIs: J. Tuckermann, A. Ignatius

Glucocorticoids (GCs) are a major pillar of the stress response upon bone fracture, but also modulate the immune response and shape bone tissue homeostasis. We found that GCs via their receptor GR, but also GC counteracting factors, influence bone integrity and fracture healing. We have strong evidence that GR deletion in skeletal stem cells/progenitor cells (SSPCs), positive for Sox9+, increases bone mass and regeneration, whereas GR deletion in Osterix (Osx, Sp7)-labeled committed osteogenic cells results in opposite effects.Beyond GR’s role as a transcriptional activator, we discovered that it regulates cellular energy metabolism and, vice versa, energy metabolites influence GR activity. Therefore, C02 hypothesizes that 1) GR influences SSPCs differentially at distinct differentiation stages and 2) GR regulation of cellular energy metabolism affects differentiation and function of SSPCs and committed osteoblasts. Using lineage tracing, transcriptional profiling and via assessment of energy metabolism in skeletal stem cells/progenitor cells and committed osteoblasts, we will elucidate the stage-specific action of GR on cellular differentiation and cell metabolism during bone regeneration after fracture in close cooperation with projects A09N, B03, B09, C03, C08 and Z02. Our results will help to better understand the role of GC signaling in fracture healing, and thus form the basis for the development of new therapies for trauma patients with healing complications.

Principle investigator

  • Prof. Dr. Jan Tuckermann
  • Universität Ulm
  • Institut für Allgemeine Zoologie und Endokrinologie 
  • Helmholtzstr. 8/1
  • 89081 Ulm
  • Tel.: +49 731 500 32600
  • Fax: +49 731 500 32609
  • jan.tuckermann(at)uni-ulm.de
  • Prof. Dr. Anita Ignatius
  • Institut für Unfallchirurgische Forschung und Biomechanik
  • Zentrum für Muskuloskelettale Forschung
  • Universitätsklinikum Ulm
  • Helmholtzstr. 14
  • 89081 Ulm
  • Tel.: +49 731 500 55301
  • Fax: +49 731 500 55302
  • anita.ignatius(at)uni-ulm.de
  • www.biomechanics.de
Glucocorticoid receptor expression (yellow) by immunofluorescence and Sox9-positive skeletal stem/progenitor cells by tdTomato expression (red) in the injury site 7 days after fracture. Grey: second harmonic generation of bone, Blue: nuclei.
Histological section of callus 10 days after fracture stained with Movat’s pentachrome.
MicroCT image of fractured femur at post-operative day 21.