Distinct Expression Patterns of Cxcl12 in Mesenchymal Stem Cell Niches of Intact and Injured Rodent Teeth.

Specific stem cell populations within dental mesenchymal tissues guarantee tooth homeostasis and regeneration throughout life. The decision between renewal and differentiation of stem cells is greatly influenced by interactions with stromal cells and extracellular matrix molecules that form the tissue specific stem cell niches. The Cxcl12 chemokine is a general marker of stromal cells and plays fundamental roles in the maintenance, mobilization and migration of stem cells. The aim of this study was to exploit Cxcl12-GFP transgenic mice to study the expression patterns of Cxcl12 in putative dental niches of intact and injured teeth. We showed that endothelial and stromal cells expressed Cxcl12 in the dental pulp tissue of both intact molars and incisors. Isolated non-endothelial Cxcl12+ dental pulp cells cultured in different conditions in vitro exhibited expression of both adipogenic and osteogenic markers, thus suggesting that these cells possess multipotent fates. Taken together, our results show that Cxcl12 is widely expressed in intact and injured teeth and highlight its importance as a key component of the various dental mesenchymal stem cell niches.

Evoked and spontaneous pain assessment during tooth pulp injury.

Injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the mouse orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. In this study we sought to address this problem using the Mouse Grimace Scale and a novel approach to the application of mechanical Von Frey hair stimuli. We use a dental pulp injury model that exposes the pulp to the outside environment, a procedure we have previously shown produces inflammation. Using RNAscope technology, we demonstrate an upregulation of genes that contribute to the pain state in the trigeminal ganglia of injured mice. We found that mice with dental pulp injury have greater Mouse Grimace Scores than sham within 24 hours of injury, suggestive of spontaneous pain. We developed a scoring system of mouse refusal to determine thresholds for mechanical stimulation of the face with Von Frey filaments. This method revealed that mice with a unilateral dental injury develop bilateral mechanical allodynia that is delayed relative to the onset of spontaneous pain. This work demonstrates that tooth pain can be quantified in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammatory pain and other forms of trigeminal pain.

Traumatic dental injuries in twins: is there a genetic risk for dental injuries?

Traumatic dental injuries are a major cause of morbidity among children. Investigation of risk factors of dental trauma is important to take preventive measures in patients at high risk for tooth accidents. The aim of this work was to conduct a pilot study in twins, assessing concordance of suffered traumatic dental and facial injuries. Comparison of concordances between monozygotic and dizygotic twin pairs was performed in order to investigate possible genetically determined accident-proneness. Standardized interviews were conducted focusing on the frequency of orofacial accidents and their circumstances. In addition, the front teeth of all participating twins were clinically examined. A total of 104 twins (52 twin pairs) were surveyed: 31 of the 52 twin pairs were DZ and 21 pairs were MZ. 36 (34.6%) of the 104 interviewees had already suffered from a tooth injury, whereas 53 (51%) of the participants had experienced a facial injury. Investigation of concordances of suffered traumatic dental injuries revealed that 66.7% of the MZ twin pairs and 58.1% of the DZ pairs were concordant. With respect to facial traumata, 52.4% of the MZ pairs compared to 58.1% of the DZ pairs were concordant. Differences between zygosity were not statistically significant (P >/= 0.05). With the present pilot study, no statistical evidence of genetic risk for dental and facial injuries could be displayed. On the contrary, environmental factors seem to dominate in determining an individual's risk for orofacial traumata.

Parallels between tooth development and repair: conserved molecular mechanisms following carious and dental injury.

The reparative mechanisms that operate following carious and traumatic dental injury are critical for pulp survival and involve a series of highly conserved processes. It appears that these processes share genetic programs-linked to cytoskeletal organization, cell movement, and differentiation-that occur throughout embryogenesis. Reactionary dentin is secreted by surviving odontoblasts in response to moderate stimuli, leading to an increase in metabolic activity. In severe injury, necrotic odontoblasts are replaced by other pulp cells, which are able to differentiate into odontoblast-like cells and produce a reparative dentin. This complex process requires the collaborative efforts of cells of different lineage. The behavior of each of the contributing cell types during the phases of proliferation, migration, and matrix synthesis as well as details of how growth factors control wound cell activities are beginning to emerge. In this review, we discuss what is known about the molecular mechanisms involved in dental repair.