title: NOTCH1 signaling regulates the BMP2/DLX-3 directed osteogenic differentiation of dental follicle cells.
abstract: Dental follicle cells (DFCs) are dental stem/progenitor cells and the genuine precursors of alveolar osteoblasts and dental cementoblasts. A previous study showed that the transcription factor DLX3 (distal less homeobox 3) supports the osteogenic differentiation in DFCs via a positive feedback loop with the bone morghogenetic protein (BMP) 2. Until today, however, the control of this BMP2/DLX3 pathway by additional signaling pathways remains elusive. Previous studies also suggested that the NOTCH signaling pathway plays a role in the osteogenic differentiation of DFCs. In this study we showed that DLX3 overexpression and the initiation of the osteogenic differentiation by BMP2 or dexamethasone induced the NOTCH signaling pathway in DFCs. However, the induction of NOTCH-signaling impaired not only the osteogenic differentiation (ALP activity and mineralized nodules) but also the expression of the transcription factor DLX3 and the activation of the BMP-signaling pathway. So, NOTCH signaling plays a regulatory role for the osteogenic differentiation of DFCs. In conclusion, results of our study suggest that the NOTCH-signaling pathway, which is activated during the osteogenic differentiation of DFCs, regulates the BMP2/DLX3 directed differentiation of DFCs via a negative feed-back loop.
authors: Department of Cranio- and Maxillofacial Surgery, University Hospital Regensburg, D-93053 Regensburg, Germany.
authors: Sandra
authors: S
authors: Viale-Bouroncle
authors: Department of Cranio- and Maxillofacial Surgery, University Hospital Regensburg, D-93053 Regensburg, Germany.
authors: Martin
authors: M
authors: Gosau
authors: Department of Cranio- and Maxillofacial Surgery, University Hospital Regensburg, D-93053 Regensburg, Germany. Electronic address: christian.morsczeck@ukr.de.
authors: Christian
authors: C
authors: Morsczeck
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003239:Connective Tissue Cells / Q000166:cytology / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D009805:Odontogenesis / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology; D051881:Receptor, Notch1; D015398:Signal Transduction / Q000502:physiology; D014070:Tooth / Q000166:cytology* / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D014157:Transcription Factors
keywords: BMP2; DLX3; Dental follicle cells; NOTCH signaling pathway; Osteogenic differentiation