CREB activation affects mesenchymal stem cell migration and differentiation in periodontal tissues due to orthodontic force

During the orthodontic tooth movement, cells in periodontal ligament could differentiate into osteoblasts to synthesize alveolar bone as well as affect the proliferation, migration and differentiation of mesenchymal stem cells, which also contribute to bone remodeling. However, the mechanism is still largely elusive. Here, we evaluated the expression of CREB at the tension site of mouse periodontal ligament under orthodontic mechanical strain and in the cyclic tension strain treated human periodontal ligament cells. Then, through gain and loss of function analysis, we revealed that CREB in PDLCs promotes SDF-1 and FGF2 secretion, which enhance the migration and osteoblastic differentiation of BMSCs. We further discovered that CREB transcriptionally activates FGF2 and SDF-1 expressions by binding to the promoter regions.In conclusion, this study confirms that CREB is an upregulated gene in periodontal ligament under orthodontic tension strain stimulation and plays an important role in regulating BMSCs' physiological activity in orthodontic tension strain-induced bone formation.