Molecular Traumatology

Denise Jahn, Jason Witte, Achim Kramer, Johannes Keller, Serafeim Tsitsilonis

Impaired bone healing occurs in around 10 percent of fractures and leads to pain, a long-term reduction in the quality of life and high socio-economic costs. More than 50 years ago, clinicians observed the phenomenon of traumatic brain injury (TBI) accelerating fracture healing. Until now, the underlying pathophysiology remained unknown, but we previously found compelling evidence that the stimulatory effect of TBI on fracture healing is transmitted through an increased adrenergic signaling, caused by an interrupted circadian clock. Several studies have shown a circadian rhythm in bone metabolism, affecting osteoclast activity, osteocytes and osteoblast function. Furthermore, the circadian clock regulates the body physiology through the sympathetic nervous system, which has a strong impact on bone tissue. Although there are a number of studies investigating the influence of the circadian clock on bone metabolism, the impact on fracture healing is largely unknown. In our project, we investigate the role of the circadian clock in fracture healing with the use of a mouse line with a disrupted circadian clock. The understanding of the role of the circadian clock in fracture healing holds great potential to aid in the development of new drugs to improve impaired bone healing.