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Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro

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Abstract

The dental follicle (DF) surrounding the developing tooth germ is an ectomesenchymal tissue composed of various cell populations derived from the cranial neural crest. Human dental follicle cells (HDFC) are believed to contain precursor cells for cementoblasts, periodontal ligament cells, and osteoblasts. Bone morphogenetic proteins (BMPs) produced by Hertwig’s epithelial root sheath or present in enamel matrix derivatives (EMD) seem to be involved in the control of DF cell differentiation, but their precise function remains largely unknown. We report the immunolocalization of STRO-1 (a marker of multipotential mesenchymal progenitor cells) and BMP receptors (BMPR) in DF in vivo. In culture, HDFC co-express STRO-1/BMPR and exhibit multilineage properties. Incubation with rhBMP-2 and rhBMP-7 or EMD for 24 h increases the expression of BMP-2 and BMP-7 by HDFC. Long-term stimulation of these cells by rhBMP-2 and/or rhBMP-7 or EMD significantly increases alkaline phosphatase activity (AP) and mineralization. Expression of cementum attachment protein (CAP) and cementum protein-23 (CP-23), two putative cementoblast markers, has been detected in EMD-stimulated whole DF and in cultured HDFC stimulated with EMD or BMP-2 and BMP-7. RhNoggin, a BMP antagonist, abolishes AP activity, mineralization, and CAP/CP-23 expression in HDFC cultures and the expression of BMP-2 and BMP-7 induced by EMD. Phosphorylation of Smad-1 and MAPK is stimulated by EMD or rhBMP-2. However, rhNoggin blocks only Smad-1 phosphorylation under these conditions. Thus, EMD may activate HDFC toward the cementoblastic phenotype, an effect mainly (but not exclusively) involving both exogenous and endogenous BMP-dependent pathways.

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Acknowledgments

The authors are grateful to Dr. P. TenDijke (The Netherlands Cancer Institute, Amsterdam, The Netherlands) and Dr. C. Heldin (Ludwig Institute for Cancer Research, Uppsala, Sweden) for providing pSmad1 antibody, and to Dr. Larry Fisher (NIH, NIDCR, Craniofacial and Skeletal Diseases Branch, Bethesda, Maryland) for providing BSP antibody. STRO-1 antibody was obtained from the Developmental Studies Hybridoma Bank (Dr. K. Jensen). HBMSC were the kind gift of Dr. P. Bourin (Etablissement Français du Sang, Toulouse, France). Dental follicles were kindly provided by Drs. F. Vaysse and B. Courtois (Faculty of Odontology, University Paul-Sabatier, Toulouse, France). The authors also thank M. Mus and A. Bros for helping with experiments.

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Authors and Affiliations

  1. Laboratory of Oral Biology, Faculty of Odontology, University Paul-Sabatier, 3 Chemin des Maraîchers, 31062, Toulouse Cedex, France

    Philippe Kémoun, Sara Laurencin-Dalicieux, Jacqueline Rue & Gérard Brunel

  2. Laboratory “Development and Regeneration of Dental Tissues”, INSERM ERI16, EA1892, IFR62, Faculty of Odontology, University Lyon 1, Rue Guillaume Paradin, 69372, Lyon Cedex 08, France

    Jean-Christophe Farges

  3. Institut Fédératif de Biologie, Clinical Biochemistry, 31059, Toulouse Cedex 9, France

    Isabelle Gennero

  4. Endocrine and Bone Diseases Unit and Growth Research Center, Children’s Hospital, 31059, Toulouse Cedex 9, France

    Françoise Conte-Auriol & Jean-Pierre Salles

  5. INSERM, U.563, Centre de Physiopathologie de Toulouse Purpan, University Paul-Sabatier, 31059, Toulouse Cedex 9, France

    Philippe Kémoun, Sara Laurencin-Dalicieux, Isabelle Gennero, Françoise Conte-Auriol, Fabienne Briand-Mesange & Jean-Pierre Salles

  6. Etablissement Français du Sang Pyrénées-Méditerranée, 75 Rue de Lisieux, 31300, Toulouse, France

    Mélanie Gadelorge

  7. Laboratorio de Biologia Celular y Molecular, Facultad de Odontologia, UNAM, Ciudad Universitaria, Coyoacan, 04510 DF, Mexico

    Higinio Arzate

  8. Department of Oral Biology, University of Washington, Health Science Building, Room B-224, Seattle, WA, 98195, USA

    A. Sampath Narayanan

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  1. Philippe Kémoun
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  2. Sara Laurencin-Dalicieux
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  9. Higinio Arzate
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  10. A. Sampath Narayanan
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  11. Gérard Brunel
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  12. Jean-Pierre Salles
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Correspondence to Jean-Pierre Salles.

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This work was supported by grants from the French Program of Hospital Clinical Research (PHRC, AOL 0304602), from the Conseil Régional de Midi Pyrénées (Cell and Gene Therapy Program), and from the Etablissement Français du Sang (Program 2003.02).

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Kémoun, P., Laurencin-Dalicieux, S., Rue, J. et al. Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro. Cell Tissue Res 329, 283–294 (2007). https://doi.org/10.1007/s00441-007-0397-3

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