Unravelling the importance of cytokines for successful bone healing
Bone fracture healing is a role model for successful endogenous regeneration, but delayed healing or non-union is a relevant clinical problem even when optimal medical treatment is available. The Federal Office of Statistics recorded 802,662 fractures in Germany in the year 2014, with 38% of the patients with fractures of the extremities older than 75 years. This indicates that bone injury is increasingly a problem occurring in elderly. Elderly patients always have an experienced (“aged”) immune system with enhanced frequencies of memory/effector cells of the adaptive immunity, thus they are in a constant systemic pro-inflammatory state. This elevated pro-inflammatory state could be a cause for the high percentages of disturbed bone healing in elderly. Fracture healing is a multistage healing process involving complex and well-orchestrated steps. In a joint effort K. Schmidt-Bleek and H-D. Volk were able to show that immune cells partake in bone healing, that they can have detrimental or beneficial effects on healing and that they also influence the resulting bone quality. These findings initiated the development of a biomarker for delayed bone healing and also the investigation of new immunomodulatory strategies to enhance bone healing.
During our research into bone regeneration the decisive role of signalling molecules expressed by immune cells has been confirmed and we have already been able to use inflammatory cytokines in a proof of concept study to change the bone healing outcome. These preliminary results lead to the hypothesis that cytokines can be used as immune modulators to enhance bone healing.
Within this PhD cytokines influencing bone healing will be analysed as well as the activation mode triggering their release. Results will be tested in a pre-clinical mouse osteotomy model with respect to potential therapeutical approaches and evaluated within a patient cohort of normal and delayed healing respectively.
1. Bucher CH, Schlundt C, Wulsten D, Sass FA, Wendler S, Ellinghaus A, Thiele T, Seemann R, Willie BM, Volk HD, Duda GN, Schmidt-Bleek K. Experience in the Adaptive Immunity Impacts Bone Homeostasis, Remodel-ing, and Healing. Front Immunol. 2019. 10:797.
2. Schlundt C, El Khassawna T, Serra A, Dienelt A, Wendler S, Schell H, van Rooijen N, Radbruch A, Lucius R, Hartmann S, Duda GN, Schmidt-Bleek K. Macrophages in bone fracture healing: Their essential role in endo-chondral ossification. Bone. 2018. 106: 78-89.