1. A protein kinase A (PKA)/β-catenin pathway sustains the BMP2/DLX3-induced osteogenic differentiation in dental follicle cells (DFCs)
- Author
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Torsten E. Reichert, Christian Morsczeck, Christoph Klingelhöffer, Tobias Ettl, and Sandra Viale-Bouroncle
- Subjects
animal structures ,Bone Morphogenetic Protein 2 ,SMAD ,Bone morphogenetic protein 2 ,Osteogenesis ,Wnt3A Protein ,Humans ,Phosphorylation ,RNA, Small Interfering ,Protein Kinase Inhibitors ,Wnt Signaling Pathway ,Transcription factor ,Cells, Cultured ,beta Catenin ,Homeodomain Proteins ,Chemistry ,Wnt signaling pathway ,Cell Differentiation ,Dental Sac ,LRP5 ,Cell Biology ,Cyclic AMP-Dependent Protein Kinases ,Recombinant Proteins ,Catenin ,embryonic structures ,Cancer research ,RNA Interference ,Signal transduction ,WNT3A ,Transcription Factors - 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.
- Published
- 2015
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