title: A protein kinase A (PKA)/β-catenin pathway sustains the BMP2/DLX3-induced osteogenic differentiation in dental follicle cells (DFCs).
abstract: The directed expression of osteogenic transcription factors via a balanced activation of signaling pathways is an important prerequisite for the development of mineralized tissues. A positive-feedback loop of the BMP2-dependent SMAD signaling pathway and the DLX3 transcription factor (BMP2/DLX3 pathway) directs the osteogenic differentiation of periodontal precursor cells from the dental follicle (DFCs). However, little is known how this BMP2/DLX3 pathway interacts with other crucial signaling pathways such as the WNT/β-catenin signaling pathway. This study investigated the interaction between the BMP2/DLX3 pathway and the WNT pathway during the osteogenic differentiation of DFCs. BMP2 induced the WNT/β-catenin pathway in DFCs and phosphorylates β-catenin via protein kinase A (PKA). Moreover, only BMP2 facilitated the binding of LEF1/SMAD4/β-catenin complex to the DLX3 promoter, while an inducer of the canonical WNT pathway, WNT3A, act as an inhibitor. Although WNT3A inhibits the osteogenic differentiation of DFCs the expression of β-catenin was crucial for both the expression of DLX3 and for the osteogenic differentiation. In conclusion, while the activation of the canonical WNT pathway inhibits the osteogenic differentiation of DFCs, β-catenin sustains the BMP2/DLX3-mediated osteogenic differentiation via the activation of PKA.
authors.affiliation: Department of Cranio- and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Viale-Bouroncle
authors.affiliation: Department of Cranio- and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Klingelhöffer
authors.affiliation: Department of Cranio- and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Ettl
authors.affiliation: Department of Cranio- and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany.
authors.forename: T E
authors.initials: TE
authors.lastname: Reichert
authors.affiliation: Department of Cranio- and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany. Electronic address: christian.morsczeck@ukr.de.
authors.forename: C
authors.initials: C
authors.lastname: Morsczeck
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003795:Dental Sac / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics*; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D055396:Bone Morphogenetic Protein 2; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D014157:Transcription Factors; D060509:Wnt3A Protein; D051176:beta Catenin; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: BMP2; DLX3; Dental follicle cells (DFCs); PKA; WNT/β-catenin pathway