Advanced Medical Scientist-Programm 2023

Thema: "The neurotrophic cytokine GDF15 - a potential epigenetic target for modulating orthodontic pain?"

Zusammenfassung:
During orthodontic therapy, 94 % of patients experiencing considerable pain with peaks around 24 hours after each treatment procedure. This should be considered critically, since it significantly affects the patient motivation and commitment to undergo and continue orthodontic therapy. Pharmacological treatment of orthodontic pain commonly targets the inflammatory component of nociceptor nerve activation. Unfortunately, this appears to be detrimental to tooth movement by impacting tissue and bone remodeling. These processes are triggered by a local aseptic inflammation modulated by periodontal ligament fibroblasts. We recently reported that GDF15, a TGF-β superfamily member, contributes to their mechanoresponse and in general agreement with other studies, our preliminary results also suggest a neurotropic role in the orthodontic context. Being discussed as potential intervention target in a variety of medical conditions, epigenetically adapting GDF15 levels by modulating histone modifications are considered as promising approach. However, with regard to orthodontics, the role of GDF15 in pain perception has not yet been addressed. Therefore, this study aims to investigate the neurotropic properties and underlying mechanisms of GDF15 in the context of orthodontic pain perception in vitro and in vivo, further focusing on the role of epigenetic regulation and a potential therapeutic inhibitor application.