Zusammenstellung von Bildern aus dem Sonderforschungsbereich

B09: Elucidating the pathomechanisms of compromised fracture healing in osteoporosis: Consequences of mitochondrial dysfunction

PIs: A. Ignatius, J. Riegger-Koch

Osteoporotic fractures are frequently associated with healing complications, but the underlying mechanisms are still unclear. Previously, we demonstrated that mitochondrial (mt) ROS accumulation in osteoblasts disturbs osteogenic differentiation, pathways involved in mitophagy/autophagy, and cellular senescence, using a new mouse model with osteoblast lineage specific Sod2 deficiency, which phenocopies age-related osteoporosis. Therefore, we hypothesize that excessive mtROS production in osteoporotic bone is a key driver of compromised fracture healing by impairing intramembranous and endochondral bone formation. Combining bone healing experiments in mice with a Sod2 deletion specifically in osteoblast lineage cells or hypertrophic chondrocytes with comprehensive in vitro studies, we aim to elucidate how excessive mtROS affect osteoblast and chondrocyte function and fate during fracture healing. We will also study whether pharmacological stabilization of mt function ameliorates compromised fracture healing in mice with mtROS-induced osteoporosis as a potential therapeutic approach. Our results will help to better understand the role of oxidative stress in fracture healing and to develop novel therapies to improve bone healing in osteoporotic patients.

Principle investigators

  • Prof. Dr. Anita Ignatius
    Institut für Unfallchirurgische Forschung und Biomechanik
    Zentrum für Traumforschung Ulm
    Universitätsklinikum Ulm
    Helmholtzstr. 14
    89081 Ulm
    Tel.: +49 731 500 55301
    Fax: +49 731 500 55302

    Dr. biol. hum. Jana Riegger-Koch
    Universitätsklinikum Ulm c/o RKU
    Sektion Biochemie für Gelenks- und Bindegewebserkrankungen
    Oberer Eselsberg 45
    89081 Ulm
    Tel.: +49 731 500 63288
    E-mail: jana.riegger(at)uni-ulm.de

Bone mass loss in osteoblast-specific Sod2-deficient female mice aged 12 and 52 weeks. Representative 2D μCT images of vertebral bodies. Upper row: 12-week-old mice, lower row 52-week-old mice. (Schoppa er al., Disease Models & Mechanisms, 2022, https://doi.org/10.1242/dmm.049392)