Cell adhesion molecules during odontogenesis and tooth-related diseases

Sammanfattning: Cell adhesion molecules play essential roles in the development and disease of tooth and oral structures, as well as in the maintenance of adult tissue structure/function. It has been shown that different types of cell adhesion molecules (CAMs) play an important part in craniofacial development when ectomesenchymal cells migrate from the neural list to the primitive oral cavity, giving rise to the palatal processes and tooth germs. The role of CAMs in craniofacial development and during odontogenesis is not well understood. Mammalian teeth, regardless of shape, have the same histological structures: enamel, dentine, pulp, cementum, and periodontal ligament. The mechanisms of tooth development include initiation, morphogenesis and cytodifferentiation. The overall aim of this study was to investigate the distribution of members of different CAM families (classical cadherins, protocadherins and IgSF) during tooth development and in tooth- related diseases. The expression pattems of the different molecules was detected by in situ hybridisation and immunohistochemistry. E-cadherin expressed at the early bell stage, in murine teeth, was located to the cells of the dental organ. By mineralisation, the pre-secretory ameloblasts were positive. At the onset of enamel secretion, repolarisation of the ameloblasts correlated with E-cadherin expression. Furthermore, E- cadherin was expressed in Hertwig's root sheath. This expression pattern was similar to that seen in human teeth. Interestingly, in normal developing human teeth, E-cadherin expression in the dental epithelium followed an apical-coronal gradient that was opposite to that observed for N-cadherin. E- cadherin was strongly expressed in proliferating epithelial cells. However, N-cadherin was detected in differentiating epithilial cells such as ameloblasts, and in differentiating mesenchymal cells such as odontoblasts. Neither E- nor N-cadherin was detected in intact permanent human teeth. Furthermore, E-cadherin was not expressed in the junctional epithelium. However, N-cadherin was reexpressed in the odontoblast surrounding a traumatic or caries lesion. Similarly, this was also observed in vitro in cultured primary pulp cells. We further investigated the expression pattems of two novel families of protocadherins (CNRs and Pcdh-gamma) during murine odontogenesis. Moreover, we compared their expression with that of reelin, which is the potential ligand of CNRs. Throughout murine odontogenesis CNRs, Pcdh-gamma, reelin and Dab 1 (an effector molecule of reelin) showed spatiotemporal expression pattems that correlated with specific morphogenetic and differentiation events. Finally, CEACAM1 has been showed to be expressed in the reduced enamel epithelium and persisted in junctional epithelium. To investigate the mechanisms behind this we used conventional rats and mice that were compared with germ-free counterparts. We found that CEACAM1 was highly expressed in the junctional epithelium and that no differences in CEACAM1 expression pattems were observed between the four groups investigated. Furthermore, the polymorphonuclear leucocyte invasion was unaltered in the four groups. In conclusion, these findings indicate that E-cadherin and N-cadherin are involved in tooth development and that N-cadherin may be involved in odontoblast differentiation or/and function under normal and pathological conditions. Furthermore, E-cadherin seems to be involved in the repolarisation process of the secretory ameloblasts. The specific spatio-temporal expression of protocadherins and reelin indicate important functions during odontogenesis. However, these expression pattems did not always correlate with Dab 1, an important effector molecule. Finally, the levels of CEACAM1 expression is probably genetically programmed and not a result of bacterial infection. Since E-cadherin was not expressed in the same tissue, we believe that CEACM 1 is important for maintaining the integrity of the junctional epithelium.