Spatial gene expression profiles within the periodontium in response to orthodontic forces

• Applicants: Professor Dr. Till Köhne; Julian Petersen, Ph.D.
• Subject Area: Dentistry, Oral Surgery
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 550694863

Our main goal is to comprehensively investigate the molecular changes in the soft and hard tissues of the periodontium following orthodontic tooth movement. To achieve this, our specific aims are as follows: In AIM 1, areas corresponding to the strain distribution upon orthodontic tooth movement in the murine periodontium will be investigated using spatial transcriptomics at various time points and with different forces. We will particularly examine spatial gene expression changes in the junctional epithelium (JE), gingiva, periodontal ligament (PDL), and surrounding bone in control mice and mice subjected to tooth movement for 1, 3, 7, and 12 days. Results from these experiments will create a high-fidelity spatiotemporal atlas of molecular responses upon orthodontic forces. In AIM 2, the collected spatial transcriptomic data from AIM 1 will be analyzed to identify differential gene expression patterns, analyze signaling pathways, and explore potential gene regulatory networks. The data will be presented on a user-friendly website that includes an interactive map and tools for researchers to easily navigate and explore the data. Anticipated results include the identification of molecular signatures associated with bone remodeling and tooth resorption. In AIM 3, we will further elucidate the potential of the data. The focus will be on identifying specific cells in the PDL, JE, and surrounding bone that respond to orthodontic forces through different signaling pathways (with a primary focus on the Wnt/β-catenin signaling pathway). Through detailed investigations, the cells and their activated signaling pathways responding to the applied forces in different regions will be determined. Molecular profiling from AIM 2 will be validated using immunohistochemistry and in situ hybridization. The results of these experiments will point to specific cells within the periodontal tissue that primarily respond to orthodontic tooth movements through certain signaling pathways. These can then be further investigated in later studies using cell-specific knockout models. Collectively, the proposed work promises to provide important new insights into the relationship between strains produced by orthodontic forces and molecular changes in the soft and hard tissues of the periodontium. Additionally, with the experimental setup, we can determine whether root resorption is a consequence of enhanced physiological processes or if it is triggered by pathological signals

• DFG Programme: Research Grants