PMID- 28116542 OWN - NLM STAT- MEDLINE DCOM- 20170414 LR - 20181113 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 428 IP - 1-2 DP - 2017 Apr TI - The hedgehog-signaling pathway is repressed during the osteogenic differentiation of dental follicle cells. PG - 79-86 LID - 10.1007/s11010-016-2918-4 [doi] AB - 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. FAU - Morsczeck, C AU - Morsczeck C AD - Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany. christian.morsczeck@ukr.de. FAU - Reck, A AU - Reck A AD - Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany. FAU - Beck, H C AU - Beck HC AD - Department of Clinical Biochemistry and Pharmacology, Centre for Clinical Proteomics, Odense University Hospital, Odense, Denmark. LA - eng PT - Journal Article DEP - 20170123 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (Hedgehog Proteins) RN - 0 (Phosphoproteins) SB - IM MH - Bone Morphogenetic Protein 2/*pharmacology MH - Cell Differentiation/drug effects MH - Cells, Cultured MH - Dental Sac/*cytology/metabolism MH - Gene Expression Regulation MH - Hedgehog Proteins/*metabolism MH - Humans MH - Osteogenesis/drug effects MH - Phosphoproteins/metabolism MH - Phosphorylation MH - Proteomics/methods MH - Signal Transduction/drug effects MH - Stem Cells/*cytology/metabolism OTO - NOTNLM OT - Bone morphogenetic protein OT - Dental follicle cells OT - Hedgehog-signaling pathway OT - Osteogenic differentiation OT - Periodontium EDAT- 2017/01/25 06:00 MHDA- 2017/04/15 06:00 CRDT- 2017/01/25 06:00 PHST- 2016/09/16 00:00 [received] PHST- 2016/12/21 00:00 [accepted] PHST- 2017/01/25 06:00 [pubmed] PHST- 2017/04/15 06:00 [medline] PHST- 2017/01/25 06:00 [entrez] AID - 10.1007/s11010-016-2918-4 [pii] AID - 10.1007/s11010-016-2918-4 [doi] PST - ppublish SO - Mol Cell Biochem. 2017 Apr;428(1-2):79-86. doi: 10.1007/s11010-016-2918-4. Epub 2017 Jan 23.