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Parallels between Tooth Development and Repair: Conserved Molecular Mechanisms following Carious and Dental Injury
T.A. Mitsiadis1,* and
C. Rahiotis2
1 Department of Craniofacial Development, Floor 27, GKT Dental Institute, King’s College, Guy’s Hospital, London Bridge, London SE1 9RT, UK; and 2 Department of Oral Biology, Dental Institute, University of Athens, Thivon 2 Street, 115 27, Goudi, Athens, Greece;
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Figure 1. Patterns of Notch2 (A), nestin (B), and N-cadherin (C,D) immunostaining in pulp cells of deciduous human teeth (About et al., 2000; Heymann et al., 2002; Mitsiadis et al., 2003). Abbreviations: d, dentin; o, odontoblasts; p, pulp; soc, sub-odontoblastic cells. Scale bars: 50 µm. Fig. 1B is reprinted from Am J Pathol 157:287–295, 2000, with permission from the American Society for Investigative Pathology. Figs. 1C and 1D are reprinted from Am J Pathol 160:2123–2133, 2002, with permission from the American Society of Investigative Pathology. Fig. 1A is reprinted from Exp Cell Res 228:101–109 (Mitsiadis et al., "Notch 2 protein...", 2003), with permission from Elsevier.
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Figure 2. Comparison between the patterns of Notch2 (D), nestin (E), and N-cadherin (F) immunostaining in human dental tissues after dental injury. (A) Schematic illustration showing reparative dentin production (asterisk) after a cavity preparation in an incisor. The blue line indicates an equivalent wounding area of a premolar shown in panel B. (B) Hematoxylin-eosin staining showing reparative dentin production (asterisk) 9 wks after class V cavity preparation (About et al., 2000). The deep blue line indicates an equivalent area shown in panel C. (C) Hematoxylin-eosin staining. Higher magnification of the reparative dentin area (asterisk) (Mitsiadis et al., 2003). (D-F) Immunostaining showing expression of Notch2 protein in sub-odontoblastic cells and blood vessels (Mitsiadis et al., 2003) (D), nestin protein in odontoblasts (About et al., 2000) (E), and N-cadherin in newly formed odontoblasts (Heymann et al., 2002) (F), after cavity preparation. Abbreviations: ab, alveolar bone; c, cementum; cav, cavity; d, dentin; e, enamel; nfo, newly formed odontoblasts; o, odontoblasts; oe, oral epithelium; p, pulp; rd, reparative dentin; soc, sub-odontoblastic cells. Scale bars: 50 µm. Figs. 2B and 2E are reprinted from Am J Pathol 157:287–295, 2000, with permission from the American Society for Investigative Pathology. Fig. 2F is reprinted from Am J Pathol 160:2123–2133, 2002, with permission from the American Society of Investigative Pathology. Figs. 2C and 2D is reprinted from Exp Cell Res 228:101–109 (Mitsiadis et al., "Notch 2 protein...", 2003), with permission from Elsevier.
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Figure 3. Patterns of Notch2 (D,E) and nestin (F,G) immunostaining in human dental tissues in different culture conditions. (A) Schematic representation showing ink diffusion (blue) from the cavity area to the dental pulp (asterisk) in a human tooth. (B) The human tooth-slice culture system. The dark blue spot shows the area where the ink-containing tube is placed, thus permitting diffusion of the ink to the dental pulp (asterisk) (Melin et al., 2000). Growth factors can be used instead of the ink to influence pulp cell activities (i.e., migration, proliferation, differentiation). (C) Diffusion of the ink (blue) through the dentin to the dental pulp (asterisk) (Melin et al., 2000). (D) In a cultured human tooth slice, Notch2 immunostaining is localized in odontoblasts and sub-odontoblastic cells (Mitsiadis et al., 2003). (E) Under the influence of TGFβ-1, Notch2 immunostaining is localized only in sub-odontoblastic cells (Mitsiadis et al., 2003). (F) Nestin immunostaining is localized around BMP4-releasing beads in cultured pulp explants (About et al., 2002). (G) Nestin immunostaining is detected in pulp cells cultured in the presence of β-glycerophosphate (About et al., 2000). Abbreviations: b, bead; cav, cavity; d, dentin; e, enamel; n, mineralized nodule; nf, nerve fibers; o, odontoblasts; p, pulp; pc, pulp chamber; pe, pulp explant; soc, sub-odontoblastic cells. Scale bars: 50 µm. Figs. 3F and 3G are reprinted from Am J Pathol 157:287–295, 2000, with permission from the American Society for Investigative Pathology. Figs. 3B and 3C are reprinted from J Dent Res 79:1689–1696, 2000, with permission from the International Association for Dental Research. Figs. 3D and 3E are reprinted from Exp Cell Res 228:101–109 (Mitsiadis et al., "Notch 2 protein...", 2003), with permission from Elsevier.
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Figure 4. Schematic representation of the molecular events occurring during reparative dentinogenesis. (A) Illustration of the reparative dentin area showing expression of AP-1, nestin, N-cadherin, and connexin 43 (Cx43) in odontoblasts, and of Notch2 in sub-odontoblastic cells. (B) Diagram showing the sequence of molecular events during tooth repair. Shorter arrows indicate early events, longer arrows late events. FGF and TGFβ molecules that are released from dentin and pulp cells activate wound healing. Abbreviations: d, dentin; o, odontoblasts; p, pulp; rd, reparative dentin; soc, sub-odontoblastic cells.
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Journal of Dental Research, Vol. 83, No. 12,
896-902 (2004)
DOI: 10.1177/154405910408301202
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