title: The hedgehog-signaling pathway is repressed during the osteogenic differentiation of dental follicle cells.
abstract: 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.
authors.affiliation: Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany. christian.morsczeck@ukr.de.
authors.forename: C
authors.initials: C
authors.lastname: Morsczeck
authors.affiliation: Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Reck
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Centre for Clinical Proteomics, Odense University Hospital, Odense, Denmark.
authors.forename: H C
authors.initials: HC
authors.lastname: Beck
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003795:Dental Sac / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D053823:Hedgehog Proteins; D010750:Phosphoproteins
keywords: Bone morphogenetic protein; Dental follicle cells; Hedgehog-signaling pathway; Osteogenic differentiation; Periodontium