Thimios Mitsiadis - Professor
Notch receptors and ligands are expressed in developing mouse teeth (Mitsiadis et al., 1997; Mitsiadis et al., 1998; Mitsiadis et al., 1995; Mitsiadis et al., 2005; Mitsiadis et al., 2010). Notch1 and Notch2 are mainly expressed in distinct epithelial cell populations (i.e. stratum intermedium, stellate reticulum) of the developing teeth that are in close contact with epithelial cells giving rise to the terminally differentiated ameloblasts, which produce the enamel matrix and express the Notch ligands Jagged1, Jagged2 and Delta1. A similar expression pattern is detected in the mesenchymal compartment of the developing teeth, where the ligands are expressed in differentiated cells (i.e. odontoblasts) producing the dentin matrix, while the Notch receptors are expressed in proliferating cells. Thus expression of the Notch ligands in teeth is complementary to that of Notch receptors. In the continuously growing rodent incisors, Notch1 and Notch2 are expressed in epithelial cell populations of the cervical loop, which represents the area where the stem cell niche is located.
Our findings in injured teeth suggest a role of Notch pathway in neovascularisation and cytodiferentiation during tooth repair. Delta1 is not expressed in intact adult teeth, while during dental pulp injury Delta1 expression is upregulated in odontoblasts and endothelial cells (Mitsiadis et al., 1999; Mitsiadis et al., 1998). Similarly, Notch receptors are not expressed in healthy adult teeth, whereas after dental injury expression of all four receptors, and especially of the Notch2 receptors, is upregulated in distinct cell populations of the dental pulp and blood vessels either close to the injury site or far away from this site (Mitsiadis et al., 1999; 2003).
More precisely, Notch2 expression is stimulated in a population of mesenchymal cells (i.e. subodontoblastic cells) after tooth injury in humans (Mitsiadis et al., 2003). Subodontoblastic cells contribute to the replacement of the disintegrating odontoblasts after injury and the formation of a reparative dentin matrix. Finally, we have identified a population of cells in vessels (i.e. pericytes) that express Notch3 following dental injury in rats (Lovschall et al., 2007). It has been suggested that pericytes represent progenitors of odontoblasts following dental injury and able to form reparative dentin. Taken together these results convince us to investigate more in details the exact role of the Notch proteins in the diverse fates of dental stem cell populations. Very recently, in collaboration with Prof. G. Pappaccio, we developed a new method of dental pulp culture for the collection of stem cells. In addition, using in vitro and in vivo techniques, we have demonstrated that periosteal and synovial stem cells from adults share common properties with mesenchymal stem cells from other origins (De Bari et al., 2008; De Bari et al., 2006; Karystinou et al., 2009). These cells can be used to form bone or cartilage in vivo when combined with biomaterials. 

Notch-Jagged
Notch-Jagged
Notch-Jagged
Notch-Jagged
Notch-Tubulin
Notch-Tubulin
Notch-Map
Notch-Map
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