Pivotal Role of Tenascin-W (-N) in Postnatal Incisor Growth and Periodontal Ligament Remodeling.

The continuously growing mouse incisor provides a fascinating model for studying stem cell regulation and organ renewal. In the incisor, epithelial and mesenchymal stem cells assure lifelong tooth growth. The epithelial stem cells reside in a niche known as the cervical loop. Mesenchymal stem cells are located in the nearby apical neurovascular bundle and in the neural plexus. So far, little is known about extracellular cues that are controlling incisor stem cell renewal and guidance. The extracellular matrix protein tenascin-W, also known as tenascin-N (TNN), is expressed in the mesenchyme of the pulp and of the periodontal ligament of the incisor, and is closely associated with collagen 3 fibers. Here, we report for the first time the phenotype of tenascin-W/TNN deficient mice, which in a C57BL/6N background exhibit a reduced body weight and lifespan. We found major defects in the alveolar bone and periodontal ligament of the growing rodent incisors, whereas molars were not affected. The alveolar bone around the incisor was replaced by a dense scar-like connective tissue, enriched with newly formed nerve fibers likely leading to periodontal pain, less food intake and reduced body weight. Using soft food to reduce mechanical load on the incisor partially rescued the phenotype. In situ hybridization and Gli1 reporter mouse experiments revealed decreased hedgehog signaling in the incisor mesenchymal stem cell compartment, which coordinates the development of mesenchymal stem cell niche. These results indicate that TNN deficiency in mice affects periodontal remodeling and increases nerve fiber branching. Through periodontal pain the food intake is reduced and the incisor renewal and the neurovascular sonic hedgehog secretion rate are reduced. In conclusion, tenascin-W/TNN seems to have a primary function in rapid periodontal tissue remodeling and a secondary function in mechanosensation.

Changes in hippocampal orexin 1 receptor expression involved in tooth pain-induced learning and memory impairment in rats.

Orexin 1 receptor signaling plays a significant role in pain as well as learning and memory processes. This study was conducted to assess the changes in orexin 1 receptor expression levels in hippocampus following learning and memory impairment induced by tooth inflammatory pulpal pain. Adult male Wistar rats received intradental injection of 100 µg capsaicin to induce pulpal pain. After recording the pain scores, spatial learning and memory were assessed using Morris Water Maze test. The hippocampal levels of orexin 1 receptor mRNA and protein were determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblotting respectively. The data showed that capsaicin-induced tooth inflammatory pulpal pain was correlated with learning and memory impairment. Intra-hippocampal injection of orexin A inhibited pain-induced learning and memory impairment. However, orexin 1 receptor antagonist, SB-334867, had no effect on learning and memory impairment. Moreover, capsaicin-induced pain significantly decreased hippocampal orexin 1 receptor mRNA and protein levels. Meanwhile, reversed changes took place in the ibuprofen-pretreated group (p < 0.05). It seems that decrease in orexin 1 receptor density and signaling could be involved in tooth pain-induced learning and memory impairment.

Genetic and environmental factors in oral health among twins.

To date, studies on the contributions of genetic factors to oral health have been inconclusive. We hypothesized that major dental diseases show a significant genetic component. The study was based on self-reported oral health among young adult twins. The data were derived from the fourth wave of the longitudinal FinnTwin16 study, in which participants completed a questionnaire in 2000-2002 enquiring about the number of filled teeth and the prevalence of gingival bleeding. We used quantitative genetic modeling, based on the genetic similarity of identical and non-identical twins, to calculate the most probable model for both filled teeth and gingival bleeding. The models revealed a strong genetic component behind the number of filled teeth, differing between males (49%) and females (68%), and a weaker genetic component affecting gingival bleeding, being similar for males and females (32%). Genetic factors contribute to inter-individual differences in oral health among young adults.

Gene expression analysis of acutely traumatized pulps.

INTRODUCTION: Vertical root fracture of vital teeth is a relatively rare occurrence. To address early molecular biologic events that take place in the pulp of such cases, we measured mRNA expression levels of selected molecules related to nociception, bacterial pattern recognition, and hard tissue repair/mineralization. METHODS: Three extracted roots obtained from vital molars diagnosed as vertical root fracture were used. The samples were first analyzed with light and transmission electron microscopy. Then mRNA expression in the apical (root fractured) and coronal portions of the pulp was analyzed by using reverse transcription-polymerase chain reaction (PCR) or real-time PCR after laser capture microdissection. RESULTS: In all the samples, cracks and vital pulp tissue, but not signs of infection and inflammation, were recognized in the apical portion of the fractured root. The gene expression analysis showed that mRNAs of pattern recognition receptors (CD14, Toll-like receptor 2, and Toll-like receptor 4) and neurokinin-1 receptor were equally expressed in both regions of the pulp. On the other hand, mRNA expression levels of hard tissue-associated proteins (osteopontin, osteonectin, and osteocalcin) and calcium channel voltage-dependent alpha 2 delta subunit 1 (CACNA2D1) in the apical portion of the pulp tissue and periodontal ligaments were significantly up-regulated, as compared with those in the coronal portion of the pulp. CONCLUSIONS: In the traumatized apical pulp of vertically root-fractured vital teeth, elevated mRNA expression of CACNA2D1, a nociception-related molecule, and proteins related to hard tissue repair/mineralization occurs under noninfectious condition.