title: The AKT signaling pathway sustains the osteogenic differentiation in human dental follicle cells.
abstract: Signaling transduction pathways are established by interactions between growth factors, protein kinases, and transcription factors, and they play a crucial role in tooth development. Precursor cells of the dental follicle (DFCs) are used for in vitro studies about molecular mechanisms during periodontal development. Previous studies have already shown that the growth factor BMP2 and the transcription factor EGR1 are involved in the osteogenic differentiation in DFCs while interactions with protein kinase-based pathways remain elusive. In this current study, we investigated the role of the AKT kinase signaling pathway for the osteogenic differentiation in DFCs. The AKT signaling pathway was activated in DFCs after the induction of the osteogenic differentiation by BMP2. The inhibition of AKT in DFCs repressed the differentiation and the expression of the transcription factor EGR1. Interestingly, EGR1 bound to the phosphorylated form of SMAD1/5 (pSMAD). The binding of pSMAD to EGR1 was increased after the induction with BMP2. Moreover, the overexpression EGR1 increased the osteogenic differentiation of DFCs. Our results suggest that the AKT signaling pathway submits the BMP2-dependent osteogenic differentiation in DFCs via the expression of the transcription factor EGR1.
authors.affiliation: Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Viale-Bouroncle
authors.forename: C
authors.initials: C
authors.lastname: Klingelhöffer
authors.forename: T
authors.initials: T
authors.lastname: Ettl
authors.forename: C
authors.initials: C
authors.lastname: Morsczeck
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D003795:Dental Sac / Q000166:cytology / Q000201:enzymology; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D004790:Enzyme Induction; D006801:Humans; D010012:Osteogenesis; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D051057:Proto-Oncogene Proteins c-akt; D000469:Alkaline Phosphatase