Immunomodulation by PDL cells under orthodontic forces

Orthodontic treatment involves the application of mechanical forces on teeth, which induce a non- infectious inflammation in the periodontal ligament (PDL). The PDL is a highly specialized structure within the periodontium, anchoring the teeth to the jawbone. This inflammation is a requirement for moving teeth into the desired position and involves increased levels of cytokines and interactions between PDL and immune cells. PDL cells respond to orthodontic forces (tension and compression) in several ways, such as releasing cytokines. An essential property of PDL cells is their ability to regulate the immune response, which is crucial for maintaining the health of the tissues around the teeth. These immunomodulatory activities are based on the production of specific immunomodulatory molecules triggered by cytokines. So far, limited research has explored how PDL cells contribute to inflammatory reactions during orthodontic tooth movement. There are no studies investigating the role of the cytokine-triggered immunomodulatory activities of PDL cells during orthodontic treatment. Hence, this study aims to elucidate the role of the immunomodulatory abilities of PDL cells during orthodontic treatment and how they help restore a healthy balance in the tissues around the teeth. More specifically, this study aims to assess how different orthodontic forces (tension and compression) affect the interaction between PDL cells and immune cells under non-infectious inflammatory conditions and how these forces functionally and mechanistically change the immunomodulatory processes within the PDL cells. We hypothesize that these forces impact the immunomodulatory abilities of PDL cells differently under various non-infectious inflammatory conditions. To investigate this, PDL cells will be treated with different cytokines and subjected to compressive and tensile mechanical forces. The treated PDL cells will be co-cultured with immune cells, and their influence on functional immune cell-related parameters will be observed. The complex interplay between immunomodulatory and biomechanical processes will be unraveled by applying single-cell RNA sequencing and knockdown approaches. Moreover, analysing the immunomediator and cytokine levels in the gingival crevicular fluid from orthodontic patients will allow us to bridge the gap between laboratory findings and the clinical situation. In summary, this study will provide a comprehensive understanding of how cytokine-induced immunomodulatory properties of PDL cells contribute to tooth movement and the associated inflammation. It will explore how orthodontic forces functionally and mechanistically influence these processes and how the immunomodulatory mechanisms of PDL cells interact with the biomechanical aspects of orthodontic treatment. The newly acquired knowledge may contribute to using the immunomodulatory mechanisms of PDL cells as a new point of action for the pharmacological acceleration of orthodontic treatment.