Project Details
Projekt
Linking traumatic brain injury and accelerated bone regeneration - a central role of alpha-adrenergic/CGRP signaling.
Subject Area
Orthopaedics, Traumatology, Reconstructive Surgery
Term
from 2016 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 326880412
Impaired fracture healing represents an ongoing clinical challenge, as treatment options remain limited. Therefore, the mechanistic understanding why traumatic brain injury (TBI) positively affects fracture repair holds great therapeutic potential. Using an experimental approach, we previously demonstrated that callus formation is increased in a mouse model combining surgically induced TBI and fracture of the femur. In our current work, we were able to elucidate the complex pathophysiologic processes linking TBI and bone regeneration in more detail. As a potential key element, we were able to identify increased alpha-adrenergic/CGRP signaling, which mediates accelerated bone regeneration following TBI. Specifically, we propose that TBI results in a temporary rise in sympathetic tone, resulting in norepinephrine (NE) release from nerve endings in the bone microenvironment. In intact bone, this leads to the inhibition of bone formation through beta-adrenergic signaling. In fractured bone however, the temporary rise of NE following TBI promotes bone regeneration through the activation of alpha-adrenergic receptors, the stimulation of local CGRP synthesis, and the activation of osteoblast precursors. Our current results raise specific questions that need to be address in order to fully understand the regulatory circuits linking bone and brain injury. The proposed study on the crosstalk between TBI and bone regeneration, as well as the comprehension of alpha-adrenergic/CGRP signaling as its putative central element, may aid in developing new therapeutic strategies for patients suffering from impaired fracture repair.
DFG Programme
Research Grants
