Dental follicle stem cells (DFCs) are precursor cells of alveolar osteoblasts, and previous studies have shown that the growth factor bone morphogenetic protein (BMP)2 induces the osteogenic differentiation of DFCs. However, the molecular mechanism down-stream of the induction of the osteogenic differentiation by BMP2 remains elusive. We investigated therefore the phosphoproteome of DFCs after the induction of the osteogenic differentiation with BMP2. In this study, phosphoproteins of the hedgehog “off” state were differentially expressed. Further analyses revealed that BMP2 induced the expression of repressors of the hedgehog-signaling pathway such as Patched 1 (PTCH1), Suppressor of Fused (SUFU), and Parathyroid Hormone-Related Peptide (PTHrP). Previous studies suggested that hedgehog proteins induce the osteogenic differentiation of mesenchymal stem cells via a paracrine pathway. Indian hedgehog (IHH) induced the expression of the osteogenic transcription factor RUNX2. However, a supplementation of the BMP2-based osteogenic differentiation medium with IHH did not induce the expression of RUNX2. Moreover, IHH inhibited slightly the ALP activity and the mineralization of osteogenic-differentiated DFCs. In conclusion, our results suggest that BMP2 inhibits the hedgehog signaling after the induction of the osteogenic differentiation in DFCs.
Hedgehog-signaling pathway Dental follicle cells Osteogenic differentiation Periodontium Bone morphogenetic protein
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Morsczeck C, Gotz W, Schierholz J et al (2005) Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol 24:155–165CrossRefPubMedGoogle Scholar
Viale-Bouroncle S, Klingelhöffer C, Ettl T et al (2014) A protein kinase A (PKA)/β-catenin pathway sustains the BMP2/DLX3-induced osteogenic differentiation in dental follicle cells (DFCs). Cell Signal. doi:10.1016/j.cellsig.2014.12.008PubMedGoogle Scholar
Viale-Bouroncle S, Felthaus O, Schmalz G et al (2012) The transcription factor DLX3 regulates the osteogenic differentiation of human dental follicle precursor cells. Stem Cells Dev 21:1936–1947. doi:10.1089/scd.2011.0422CrossRefPubMedGoogle Scholar
Melo-Braga MN, Meyer M, Zeng X, Larsen MR (2015) Characterization of human neural differentiation from pluripotent stem cells using proteomics/PTMomics–current state-of-the-art and challenges. Proteomics 15:656–674. doi:10.1002/pmic.201400388CrossRefPubMedGoogle Scholar
Klingelhöffer C, Reck A, Ettl T, Morsczeck C (2016) The parathyroid hormone-related protein is secreted during the osteogenic differentiation of human dental follicle cells and inhibits the alkaline phosphatase activity and the expression of DLX3. Tissue Cell 48:334–339. doi:10.1016/j.tice.2016.05.007CrossRefPubMedGoogle Scholar