Abstract
Signaling transduction pathways are established by interactions between growth factors, protein kinases, and transcription factors, and they play a crucial role in tooth development. Precursor cells of the dental follicle (DFCs) are used for in vitro studies about molecular mechanisms during periodontal development. Previous studies have already shown that the growth factor BMP2 and the transcription factor EGR1 are involved in the osteogenic differentiation in DFCs while interactions with protein kinase-based pathways remain elusive. In this current study, we investigated the role of the AKT kinase signaling pathway for the osteogenic differentiation in DFCs. The AKT signaling pathway was activated in DFCs after the induction of the osteogenic differentiation by BMP2. The inhibition of AKT in DFCs repressed the differentiation and the expression of the transcription factor EGR1. Interestingly, EGR1 bound to the phosphorylated form of SMAD1/5 (pSMAD). The binding of pSMAD to EGR1 was increased after the induction with BMP2. Moreover, the overexpression EGR1 increased the osteogenic differentiation of DFCs. Our results suggest that the AKT signaling pathway submits the BMP2-dependent osteogenic differentiation in DFCs via the expression of the transcription factor EGR1.
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References
Sodek J, McKee MD (2000) Molecular and cellular biology of alveolar bone. Periodontol 24:99–126
Chai Y, Maxson RE Jr (2006) Recent advances in craniofacial morphogenesis. Dev Dyn Off Publ Am Assoc Anat 235:2353–2375. doi:10.1002/dvdy.20833
Ten Cate AR (1997) The development of the periodontium—a largely ectomesenchymally derived unit. Periodontol 2000(13):9–19
Morsczeck C, Götz W, Schierholz J et al (2005) Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol J Int Soc Matrix Biol 24:155–165. doi:10.1016/j.matbio.2004.12.004
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.2011.0422
Depew MJ, Simpson CA, Morasso M, Rubenstein JLR (2005) Reassessing the Dlx code: the genetic regulation of branchial arch skeletal pattern and development. J Anat 207:501–561. doi:10.1111/j.1469-7580.2005.00487.x
Choi YH, Choi H-J, Lee K-Y, Oh J-W (2012) Akt1 regulates phosphorylation and osteogenic activity of Dlx3. Biochem Biophys Res Commun 425:800–805. doi:10.1016/j.bbrc.2012.07.155
Gu Y-X, Du J, Si M-S et al (2013) The roles of PI3K/Akt signaling pathway in regulating MC3T3-E1 preosteoblast proliferation and differentiation on SLA and SLActive titanium surfaces. J Biomed Mater Res A 101A:748–754. doi:10.1002/jbm.a.34377
Platt MO, Wilder CL, Wells A et al (2009) Multipathway kinase signatures of multipotent stromal cells are predictive for osteogenic differentiation: tissue-specific stem cells. Stem Cells Dayt Ohio 27:2804–2814. doi:10.1002/stem.215
Ghosh-Choudhury N, Abboud SL, Nishimura R et al (2002) Requirement of BMP-2-induced phosphatidylinositol 3-kinase and Akt serine/threonine kinase in osteoblast differentiation and Smad-dependent BMP-2 gene transcription. J Biol Chem 277:33361–33368. doi:10.1074/jbc.M205053200
Yu J, Zhang SS, Saito K et al (2009) PTEN regulation by Akt-EGR1-ARF-PTEN axis. EMBO J 28:21–33. doi:10.1038/emboj.2008.238
Chu L, Wang T, Hu Y et al (2013) Activation of Egr-1 in human lung epithelial cells exposed to silica through MAPKs signaling pathways. PLoS ONE 8:e68943. doi:10.1371/journal.pone.0068943
Sukhatme VP, Cao XM, Chang LC et al (1988) A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization. Cell 53:37–43
Hofer G, Grimmer C, Sukhatme VP et al (1996) Transcription factor Egr-1 regulates glomerular mesangial cell proliferation. J Biol Chem 271:28306–28310
Press T, Viale-Bouroncle S, Felthaus O et al (2014) EGR1 supports the osteogenic differentiation of dental stem cells. Int Endod J. doi:10.1111/iej.12299
Viale-Bouroncle S, Gosau M, Morsczeck C (2014) Laminin regulates the osteogenic differentiation of dental follicle cells via integrin-α2/-β1 and the activation of the FAK/ERK signaling pathway. Cell Tissue Res. doi:10.1007/s00441-014-1869-x
Viale-Bouroncle S, Gosau M, Morsczeck C (2014) Collagen I induces the expression of alkaline phosphatase and osteopontin via independent activations of FAK and ERK signalling pathways. Arch Oral Biol 59:1249–1255. doi:10.1016/j.archoralbio.2014.07.013
Pantovic A, Krstic A, Janjetovic K et al (2013) Coordinated time-dependent modulation of AMPK/Akt/mTOR signaling and autophagy controls osteogenic differentiation of human mesenchymal stem cells. Bone 52:524–531. doi:10.1016/j.bone.2012.10.024
Mukherjee A, Wilson EM, Rotwein P (2010) Selective signaling by Akt2 promotes bone morphogenetic Protein 2-mediated osteoblast differentiation. Mol Cell Biol 30:1018–1027. doi:10.1128/MCB.01401-09
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.2014.12.008
Saugspier M, Felthaus O, Viale-Bouroncle S et al (2010) The differentiation and gene expression profile of human dental follicle cells. Stem Cells Dev 19:707–717. doi:10.1089/scd.2009.0027
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Viale-Bouroncle, S., Klingelhöffer, C., Ettl, T. et al. The AKT signaling pathway sustains the osteogenic differentiation in human dental follicle cells. Mol Cell Biochem 406, 199–204 (2015). https://doi.org/10.1007/s11010-015-2437-8
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DOI: https://doi.org/10.1007/s11010-015-2437-8