Hirotaka Kikuchi

Tumor Specificity and the Type of Cell Death Induced by Heterocycles

Considering the presence of multiple types of cell death induced by chemicals, it is important to determine a definitive strategy for the exploration of new highly tumor-selective compounds. The screening of highly selective compounds should be performed before the identification of the type of cell death (either apoptosis, autophagy, or necrosis) and the cell death induction mechanism. The tumor specificities of heterocyclic compounds and the type of cell death induced by them are summarized.

Hyaluronan induces odontoblastic differentiation of dental pulp stem cells via CD44

BackgroundDental pulp tissue contains many undifferentiated mesenchymal cells, which retain the ability to differentiate into mature cells. Induced pluripotent stem cells have been developed from various cell sources, including dental pulp-derived stem cells, and evaluated for potential application to regenerative therapy. Dental pulp tissues overexpress CD44, a cell-adhesion factor involved in the induction of mineralization. In this study, we investigated the effects of hyaluronan—a known CD44 ligand—on dental pulp stem cells (DPSCs).MethodsDPSC CD44 expression was analyzed using immunofluorescence staining, flow cytometry, and western blotting. Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Effects of hyaluronan on the cell cycle were analyzed by flow cytometry. Alkaline phosphatase activity was employed as marker of mineralization and measured by fluorometric quantification and western blotting. Bone morphogenetic protein (BMP)-2, BMP-4, dentin sialophosphoprotein (DSPP), and dentin matrix acidic phosphoprotein 1 (DMP-1) levels were measured using real-time polymerase chain reaction. Odontoblastic differentiation and the close cell signaling examination of DPSC differentiation were determined using western blotting.ResultsHyaluronan induced expression of the odontoblastic differentiation markers DMP-1 and DSPP. Moreover, the odontoblastic differentiation induced by hyaluronan was mediated by CD44—but not by Akt, Smad1 or MAPK signaling.ConclusionsOur results indicate that hyaluronan induces odontoblastic differentiation of DPSCs via CD44. This suggests that hyaluronan plays a crucial role in the induction of odontoblastic differentiation from DPSCs. Our findings may aid the development of new, inexpensive, and effective conservative treatments for dental pulp repair.

Adhesion of Porphyromonas gingivalis to Hybrid Restorative Materials.

近年, 優れた物性と色調再現性をその主たる特徴とするハイブリッド修復材料が開発され臨床応用されてきているが, 歯周病原性細菌の易付着性という見地からの評価は十分なされていない。そこで, 3種類のハイブリッド修復材料 (エステニア®アートグラス®コンクエスト™), および従来から修復材として用いられている常温重合レジン (即時重合レジン), 20K金合金について, それぞれの表面粗さおよびPorphyromonas gdngivalis (P. gingivalis) 付着量, さらにヒト・モノサイト細胞株THP-1 (THP-1) を用いた細胞傷害性の有無について検討を行った。その結果, 3種類のハイブリッド修復材の表面粗さは20K金合金に次いで滑沢であり, 常温重合レジンが最も粗かった。細菌付着量は, 20K金合金, ハイブリッド歯冠修復材料の順表に増大し, 表面粗さとP. gingivalisの付着量とは相関することが示唆された。また, 細胞傷害性は, どの材料にも認められなかった。これらのことからハイブリッド修復材料は歯周病学的にも臨床での応用が期待される材料であることが示唆された。