Molecular aspects of tooth pathogenesis and repair: in vivo and in vitro models.
Several growth factors and extracellular matrix molecules, which are expressed during embryonic tooth development, are re-expressed in dental tissues under pathological conditions. Pathological conditions such as caries lesions and dental injuries are often lethal to the odontoblasts, which are then replaced by other pulp cells. These cells are able to differentiate into odontoblast-like cells and produce a reparative dentin. Here we demonstrate the in vivo distribution of several molecules in human permanent teeth under normal and pathological conditions. The intermediate filament protein nestin, which is a marker of young odontoblasts, is absent from old permanent teeth. Similarly, the Notch protein, which is involved in cell fate specification and is localized in the sub-odontoblastic cell layer during odontogenesis, is not detected in adult dental tissues. In carious and injured teeth, nestin is expressed in a selective manner in odontoblasts surrounding the injury site, while Notch is expressed in the sub-odontoblastic layer of cells. We reproduced this physiological event in an in vitro culture system. Pulp cells cultured in the presence of beta-glycerophosphate formed mineralization nodules. As odontoblasts, pulp cells contributing to the nodule formation express type I collagen, osteonectin, dentin sialophosphoprotein, and nestin. In this in vitro assay system, nestin is up-regulated after local application of Bone Morphogenetic Protein 2 and 4. Fourier transform infrared microspectroscopy showed that both the organic and the mineral compositions of the nodules have the characteristics of human dentin and differ from those of enamel and bone. These findings show that both the molecular and the mineral characteristics of the human dentin matrix are respected in the in vitro culture conditions.
About
I
I
Faculté d'Odontologie, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille, France.
Mitsiadis
T A
TA
D000328:Adult; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D024042:Collagen Type I / Q000096:biosynthesis; D046508:Culture Techniques; D003731:Dental Caries / Q000503:physiopathology; D003782:Dental Pulp / Q000166:cytology / Q000378:metabolism; D003804:Dentin / Q000502:physiology* / Q000503:physiopathology; D003809:Dentin, Secondary / Q000502:physiology; D003810:Dentinogenesis / Q000502:physiology*; D016326:Extracellular Matrix Proteins; D005333:Fetus; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000096:biosynthesis; D008565:Membrane Proteins / Q000032:analysis; D009419:Nerve Tissue Proteins; D064231:Nestin; D009804:Odontoblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009805:Odontogenesis / Q000502:physiology; D015676:Osteonectin / Q000096:biosynthesis; D010750:Phosphoproteins / Q000096:biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis; D051880:Receptors, Notch; D012795:Sialoglycoproteins; D017550:Spectroscopy, Fourier Transform Infrared; D014074:Tooth Calcification / Q000502:physiology; D014076:Tooth Diseases / Q000503:physiopathology*; D018677:Tooth Injuries / Q000503:physiopathology; D015534:Trans-Activators / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation; D000099311:Dentin Sialophosphoprotein
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D015676:Osteonectin; D010750:Phosphoproteins; D011498:Protein Precursors; D051880:Receptors, Notch; D012795:Sialoglycoproteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D000099311:Dentin Sialophosphoprotein; C525718:BMP2 protein, human; C525809:BMP4 protein, human; C577484:NES protein, human