Clinical Oral Investigations

, 13:383 | Cite as

Gene expression profiles of dental follicle cells before and after osteogenic differentiation in vitro

  • Christian MorsczeckEmail author
  • Gottfried Schmalz
  • Torsten Eugen Reichert
  • Florian Völlner
  • Michael Saugspier
  • Sandra Viale-Bouroncle
  • Oliver Driemel
Original Article


Recently, osteogenic precursor cells were isolated from human dental follicles, which differentiate into cementoblast- or osteoblast-like cells under in vitro conditions after the induction with dexamethasone or insulin. However, mechanisms for osteogenic differentiation are not understood in detail. In a previous study, real-time RT-PCR results demonstrated molecular mechanisms in dental follicle cells (DFCs) during osteogenic differentiation that are different from those in bone-marrow-derived mesenchymal stem cells. We analysed gene expression profiles in DFCs before and after osteogenic differentiation with the Affymetrix GeneChip® Human Gene 1.0 ST Array. Transcripts of 98 genes were up-regulated after differentiation. These genes could be clustered into subcategories such as cell differentiation, cell morphogenesis, and skeletal development. Osteoblast-specific transcription factors like osterix and runx2 were constitutively expressed in differentiated DFCs. In contrast, the transcription factor ZBTB16, which promotes the osteoblastic differentiation of mesenchymal stem cells as an up-stream regulator of runx2, was differentially expressed after differentiation. Transcription factors NR4A3, KLF9 and TSC22D3, involved in the regulation of cellular development, were up-regulated as well. In conclusion, we present the first transcriptome of human DFCs before and after osteogenic differentiation. This study sheds new light on the complex mechanism of osteogenic differentiation in DFCs.


Dental follicle Microarray Osteogenic differentiation ZBTB16 



This work was supported by the DFG (Deutsche Forschungsgemeinschaft) MO1875/2-1. We thank the “Centre of Excellence for Fluorescent Bioanalytics” of the University of Regensburg for the realisation of microarray hybridizations and Dr. Thomas Langmann for his support in the evaluation of raw-data. Finally, we would like to thank Dr. Merle Windgassen-Morsczeck for careful reading and valuable suggestions.

Conflict of interest

Authors declare that they have no conflict of interests.

Supplementary material

784_2009_260_MOESM1_ESM.docx (25 kb)
Supplemental Table Genes regulated after osteogenic differentiation (DOCX 25 kb)


  1. 1.
    Ten Cate AR (1997) The development of the periodontium—a largely ectomesenchymally derived unit. Periodontol 2000 13:9–19CrossRefPubMedGoogle Scholar
  2. 2.
    Morsczeck C, Schmalz G, Reichert TE, Vollner F, Galler K, Driemel O (2008) Somatic stem cells for regenerative dentistry. Clin Oral Investig 12:113–118CrossRefPubMedGoogle Scholar
  3. 3.
    Morsczeck C, Gotz W, Schierholz J, Zeilhofer F, Kuhn U, Mohl C, Sippel C, Hoffmann KH (2005) Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol 24:155–165CrossRefPubMedGoogle Scholar
  4. 4.
    Morsczeck C, Moehl C, Gotz W, Heredia A, Schaffer TE, Eckstein N, Sippel C, Hoffmann KH (2005) In vitro differentiation of human dental follicle cells with dexamethasone and insulin. Cell Biol Int 29:567–575CrossRefPubMedGoogle Scholar
  5. 5.
    Kemoun P, Laurencin-Dalicieux S, Rue J, Farges JC, Gennero I, Conte-Auriol F, Briand-Mesange F, Gadelorge M, Arzate H, Narayanan AS, Brunel G, Salles JP (2007) Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro. Cell Tissue Res 329:283–294CrossRefPubMedGoogle Scholar
  6. 6.
    Morsczeck C (2006) Gene expression of runx2, Osterix, c-fos, DLX-3, DLX-5, and MSX-2 in dental follicle cells during osteogenic differentiation in vitro. Calcif Tissue Int 78:98–102CrossRefPubMedGoogle Scholar
  7. 7.
    Winer J, Jung CK, Shackel I, Williams PM (1999) Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro. Anal Biochem 270:41–49CrossRefPubMedGoogle Scholar
  8. 8.
    Scherf M, Epple A, Werner T (2005) The next generation of literature analysis: integration of genomic analysis into text mining. Brief Bioinform 6:287–297CrossRefPubMedGoogle Scholar
  9. 9.
    Seifert M, Scherf M, Epple A, Werner T (2005) Multievidence microarray mining. Trends Genet 21:553–558CrossRefPubMedGoogle Scholar
  10. 10.
    Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4:3CrossRefGoogle Scholar
  11. 11.
    Bansal MP, Kaur P (2005) Selenium, a versatile trace element: current research implications. Indian J Exp Biol 43:1119–1129PubMedGoogle Scholar
  12. 12.
    Livesey FJ (1999) Netrins and netrin receptors. Cell Mol Life Sci 56:62–68CrossRefPubMedGoogle Scholar
  13. 13.
    Abdallah BM, Boissy P, Tan Q, Dahlgaard J, Traustadottir GA, Kupisiewicz K, Laborda J, Delaisse JM, Kassem M (2007) dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by modulating gene expression of pro-inflammatory cytokines and immune response-related factors. J Biol Chem 282:7339–7351CrossRefPubMedGoogle Scholar
  14. 14.
    Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084CrossRefPubMedGoogle Scholar
  15. 15.
    Sze SK, de Kleijn DP, Lai RC, Khia Way TE, Zhao H, Yeo KS, Low TY, Lian Q, Lee CN, Mitchell W, El Oakley RM, Lim SK (2007) Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells. Mol Cell Proteomics 6:1680–1689CrossRefPubMedGoogle Scholar
  16. 16.
    Hou W, Medynski D, Wu S, Lin X, Li LY (2005) VEGI-192, a new isoform of TNFSF15, specifically eliminates tumor vascular endothelial cells and suppresses tumor growth. Clin Cancer Res 11:5595–5602CrossRefPubMedGoogle Scholar
  17. 17.
    Hardy K, Mansfield L, Mackay A, Benvenuti S, Ismail S, Arora P, O’Hare MJ, Jat PS (2005) Transcriptional networks and cellular senescence in human mammary fibroblasts. Mol Biol Cell 16:943–953CrossRefPubMedGoogle Scholar
  18. 18.
    Mullican SE, Zhang S, Konopleva M, Ruvolo V, Andreeff M, Milbrandt J, Conneely OM (2007) Abrogation of nuclear receptors Nr4a3 and Nr4a1 leads to development of acute myeloid leukemia. Nat Med 13:730–735CrossRefPubMedGoogle Scholar
  19. 19.
    Ayroldi E, Zollo O, Bastianelli A, Marchetti C, Agostini M, Di VR, Riccardi C (2007) GILZ mediates the antiproliferative activity of glucocorticoids by negative regulation of Ras signaling. J Clin Invest 117:1605–1615CrossRefPubMedGoogle Scholar
  20. 20.
    Robertson EJ, Charatsi I, Joyner CJ, Koonce CH, Morgan M, Islam A, Paterson C, Lejsek E, Arnold SJ, Kallies A, Nutt SL, Bikoff EK (2007) Blimp1 regulates development of the posterior forelimb, caudal pharyngeal arches, heart and sensory vibrissae in mice. Development 134:4335–4345CrossRefPubMedGoogle Scholar
  21. 21.
    Kim M, Li D, Cui Y, Mueller K, Chears WC, DeJong J (2006) Regulatory factor interactions and somatic silencing of the germ cell-specific ALF gene. J Biol Chem 281:34288–34298CrossRefPubMedGoogle Scholar
  22. 22.
    Simmen FA, Xiao R, Velarde MC, Nicholson RD, Bowman MT, Fujii-Kuriyama Y, Oh SP, Simmen RC (2007) Dysregulation of intestinal crypt cell proliferation and villus cell migration in mice lacking Kruppel-like factor 9. Am J Physiol Gastrointest Liver Physiol 292:G1757–G1769CrossRefPubMedGoogle Scholar
  23. 23.
    Ikeda R, Yoshida K, Tsukahara S, Sakamoto Y, Tanaka H, Furukawa K, Inoue I (2005) The promyelotic leukemia zinc finger promotes osteoblastic differentiation of human mesenchymal stem cells as an upstream regulator of CBFA1. J Biol Chem 280:8523–8530CrossRefPubMedGoogle Scholar
  24. 24.
    Xu X, Mannik J, Kudryavtseva E, Lin KK, Flanagan LA, Spencer J, Soto A, Wang N, Lu Z, Yu Z, Monuki ES, Andersen B (2007) Co-factors of LIM domains (Clims/Ldb/Nli) regulate corneal homeostasis and maintenance of hair follicle stem cells. Dev Biol 312:484–500CrossRefPubMedGoogle Scholar
  25. 25.
    Bai G, Sheng N, Xie Z, Bian W, Yokota Y, Benezra R, Kageyama R, Guillemot F, Jing N (2007) Id sustains Hes1 expression to inhibit precocious neurogenesis by releasing negative autoregulation of Hes1. Dev Cell 13:283–297CrossRefPubMedGoogle Scholar
  26. 26.
    Ciarrocchi A, Jankovic V, Shaked Y, Nolan DJ, Mittal V, Kerbel RS, Nimer SD, Benezra R (2007) Id1 restrains p21 expression to control endothelial progenitor cell formation. PLoS ONE 2:e1338CrossRefPubMedGoogle Scholar
  27. 27.
    Felty Q, Porther N (2008) Estrogen-induced redox sensitive Id3 signaling controls the growth of vascular cells. Atherosclerosis 198:12–21CrossRefPubMedGoogle Scholar
  28. 28.
    Schuller U, Zhao Q, Godinho SA, Heine VM, Medema RH, Pellman D, Rowitch DH (2007) Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors. Mol Cell Biol 27:8259–8270CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Christian Morsczeck
    • 1
    • 2
    Email author
  • Gottfried Schmalz
    • 1
  • Torsten Eugen Reichert
    • 3
  • Florian Völlner
    • 1
    • 2
  • Michael Saugspier
    • 2
  • Sandra Viale-Bouroncle
    • 1
    • 2
  • Oliver Driemel
    • 3
  1. 1.Department of Operative Dentistry and PeriodontologyUniversity of RegensburgRegensburgGermany
  2. 2.Institute of Human GeneticsUniversity of RegensburgRegensburgGermany
  3. 3.Department of Oral and Maxillofacial SurgeryUniversity of RegensburgRegensburgGermany

Personalised recommendations