（川島伸之、COE特任講師、1962生）
| ・ | Research Associate Professor（Junior）, Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone |
| ・ | Department of Pulp Biology and Endodontics, Graduate School, Tokyo Medical and Dental University |
Profile
My research field, which is based on the pulp biological curiosity, is categorized into four areas : the pulpal immuno-defense system, the periapical bone destruction, the mineralization mechanisms, and the odontoblast differentiation.
The main powers in the pulpal defense system are macrophages and dendritic cells that exist not only in the central portion of the pulp tissue but in the pulp-dentin border, and extend their cytoplasmic processes into the dentinal tubules as if they intend to catch the exogenous stimuli. They should work effectively to remove harmful challenges invading through dentinal tubules. If the exogenous stimuli are too strong to be coped with this innate immune system, the pulpitis is evoked and a variety of chemical mediators are produced in the course of inflammation. We found that nitric oxide is one of the key mediators in the pulpal inflammation, and blockade of its synthesis would be effective to cause the arrest of pulpal inflammation.
Following the progress of pulpal inflammation, the periapical tissue became the second defense line against bacterial invasion. The influx of macrophages into the periapical area at the beginning of periapical inflammation induces the production of abundant proinflammatory cytokines synthesis, which would induce periapical bone destruction. Initiation of the anti inflammatory cytokine synthesis should be a sign of transition from“acute”to“chronic”. Therefore, the balance between pro-inflammatory and antiinflammatory cytokines should be the point on the progress of periapical lesions. In addition, RANKL expression was correlated to the periapical bone resorption.
On order to reconstruct the bone defects around the root apex induced in the periapical lesions, not only the removal of bacterial challenges but induction of osteoblasts, which are the leads of mineralization, is essential. In the course of osteoblast differentiation and maturation, the importance of Notch signaling was clarified. Introduction of constitutive Notch signaling into the osteoblastic cell line : Kusa-A1 caused down-regulation of osteoblastic maker expression in vitro and mineralization in vivo. Controls on the Notch signaling in the osteoblasts might be effective to induce hard tissue formation.
My last research area is the odontoblast differentiation and the characterization of pulp cells, and is also my main program in this COE project. In the course of tooth development, dental pulp cells differentiate into odontoblasts under the effects from the epithelial cells of inner enamel, and they also possess a capacity to differentiate into odontoblasts after a severe injury even in the absence of epithelial cells in the mature dental pulp tissue. However, the mechanisms of the odontoblast differentiation are still unclear. Gene expression profiling in the pulp tissue may reveal some candidates of essential genes for pulpal cells. Whether they are the key factors in odontoblast differentiation would be confirmed through this project.
These four areas are relating to one another closely, and should be essential to induce the regeneration or reconstruction of pulpal and periapical tissues, which is my ultimate goal as a clinical endodontist.
1. Kawashima N, et al.. Immunology. 1999；97（1）：117-23.
2. Kawashima N, et al.. Arch Oral Biol. 1999；44（1）：55-66.