Title: 0625 - The Molecular Signature of Orthodontic Tooth Movement – A Time Course In-Vivo Analysis
Yehuda Klein (Presenter)
Faculty of Dental Medicine, Hebrew University-Hadassah School of Dental Medicine, Israel
David Polak, hadassah medical center - hebrew university
Offir Levin, Faculty of Dental Medicine, Hebrew University-Hadassah School of Dental Medicine, Israel
Sharona Elgavish, Hebrew University-Hadassah school of Medicine
Yuval Nevo, Hebrew University-Hadassah school of Medicine
Hadar Benyamini, Hebrew University-Hadassah school of Medicine
Omer Fleissig, Hebrew University
Stella Chaushu, Hebrew University
Objectives: New therapeutic interventions for orthodontic tooth movement (OTM) modulation have constantly been proposed. However, biological approaches lack a full understanding of the underlying molecular mechanisms. Here we aimed to provide a time-course gene expression profile of OTM in a mouse model.
Methods: Ni-Ti springs were set between upper left first molars and upper incisors of C57BL/6 mice. Total RNAs were extracted from dissected tissue blocks 1,3,7,14 days post force initiation and from 2 control groups (naïve and inactivated spring). Gene expression profiles were investigated using next generation RNA sequencing. Gene Set Enrichment Analysis (GSEA) was used to infer the gene function as time course dependency. K-means algorithm and Pathway analysis method were used to identify gene clusters according to their changing expression pattern. Genes of interest were validated by qRT-PCR (P<0.05).
Results: 3075 differentially expressed genes(DEGs) were identified, with the highest number found in day 3. GSEA of first days showed upregulation of DEGs associated with inflammatory response, complement immune reaction, allograft rejection, DNA repair and synthesis, cell cycle regulation and coagulation. These pathways were downregulated in day 14 and others, such as hypoxia, apoptosis, cell proliferation, epithelial to mesenchymal transition, wound healing and angiogenesis were upregulated. Among the 10 gene clusters found, two distinct patterns were recognized. Those in which DEG’s peaked in the first days and declined afterwards identified pathways related to cytoskeleton signaling, tissue degradation, phagocytosis, leukocyte extravasation, innate immune system response, mediators between innate and adaptive immunity and blood vessels formation. In contrast, clusters in which DEG’s were initially downregulated and increased at day 14 identified pathways related to cell proliferation and migration, cytoskeletal rearrangement, tissue homeostasis and immune cell chemotaxis. qRT-PCR exhibited a high level of agreement with RNA-seq.
Conclusions: This is the first in vivo report of the gene expression signature of OTM, in a time dependent manner. The gene sets constitute attractive targets for future studies into the molecular OTM modulation and will contribute finding novel therapeutic means to clinically control it.
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE