title: Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro.
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.
authors: Laboratory of Oral Biology, Faculty of Odontology, University Paul-Sabatier, 3 Chemin des Maraîchers, 31062, Toulouse Cedex, France.
authors: Philippe
authors: P
authors: Kémoun
authors: Sara
authors: S
authors: Laurencin-Dalicieux
authors: Jacqueline
authors: J
authors: Rue
authors: Jean-Christophe
authors: JC
authors: Farges
authors: Isabelle
authors: I
authors: Gennero
authors: Françoise
authors: F
authors: Conte-Auriol
authors: Fabienne
authors: F
authors: Briand-Mesange
authors: Mélanie
authors: M
authors: Gadelorge
authors: Higinio
authors: H
authors: Arzate
authors: A Sampath
authors: AS
authors: Narayanan
authors: Gérard
authors: G
authors: Brunel
authors: Jean-Pierre
authors: JP
authors: Salles
mesh_terms: D000293:Adolescent; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D002648:Child; D003739:Dental Cementum / Q000378:metabolism / Q000502:physiology*; D003746:Dental Enamel Proteins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D003795:Dental Sac / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000494:pharmacology; D051898:Smad1 Protein / Q000378:metabolism / Q000502:physiology; D046509:Tissue Culture Techniques; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*
chemical_list: C525718:BMP2 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D003746:Dental Enamel Proteins; D011994:Recombinant Proteins; C497399:SMAD1 protein, human; D051898:Smad1 Protein; D016212:Transforming Growth Factor beta; C109069:enamel matrix proteins; D020928:Mitogen-Activated Protein Kinases; D052004:Bone Morphogenetic Protein Receptors; D000469:Alkaline Phosphatase