Morsczeck C, Reck A, Beck H C
Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
Department of Clinical Biochemistry and Pharmacology, Centre for Clinical Proteomics, Odense University Hospital, Odense, Denmark.
Mol Cell Biochem. 2017 Apr;428(1-2):79-86. doi: 10.1007/s11010-016-2918-4. Epub 2017 Jan 23.
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.
牙囊干细胞（DFCs）是牙槽成骨细胞的前体细胞，先前的研究表明生长因子骨形态发生蛋白（BMP）2可诱导DFCs的成骨分化。然而，BMP2诱导成骨分化的下游分子机制仍不清楚。因此，我们研究了用BMP2诱导成骨分化后DFCs的磷酸化蛋白质组。在本研究中，处于刺猬信号“关闭”状态的磷酸化蛋白表达存在差异。进一步分析表明，BMP2诱导了刺猬信号通路抑制因子的表达，如patched 1（PTCH1）、融合抑制因子（SUFU）和甲状旁腺激素相关肽（PTHrP）。先前的研究表明，刺猬蛋白通过旁分泌途径诱导间充质干细胞的成骨分化。印度刺猬（IHH）诱导成骨转录因子RUNX2的表达。然而，在基于BMP2的成骨分化培养基中添加IHH并不能诱导RUNX2的表达。此外，IHH略微抑制了成骨分化DFCs的碱性磷酸酶（ALP）活性和矿化。总之，我们的结果表明，BMP2在诱导DFCs成骨分化后抑制了刺猬信号通路。
