PubMed Health⌕ Search

Biomedical subjects

E Fukumoto

Publications and source records attributed to E Fukumoto.

5 recordsLinked to original sources

Cadherin-related neuronal receptors in incisor development.

Cadherins are cell adhesion molecules that are critical for tissue development. In this report, we identified members of the cadherin family cadherin-related neuronal receptors (CNRs) 1 and 5 expressed in rat incisors by the differential display method. Quantitative RT-PCR revealed that CNR1 mRNA is expressed in the secretory stage but reduced in the early-maturation stage, while CNR5 mRNA is expressed in both these stages. In situ hybridization showed that strong expression of CNR1 is strong in the secretory stage, but reduced in the early phase and diminished in the late phase of the early-maturation stage. CNR5 mRNA is expressed almost at the same levels in the secretory and in the early phase of the early-maturation stages but is absent in the late phase of the early-maturation stage. Both CNR1 and 5 mRNA are continuously expressed in odontoblasts. Immunohistology showed that CNR proteins are expressed in the secretory and early-maturation stages of ameloblasts, but no protein expression at the late-maturation stage was observed. CNR proteins were continuously expressed in odontoblasts. We found that recombinant CNR1 binds dental epithelial and mesenchymal cells through N-terminal domain EC1 in vitro. These results suggest that CNR1 and CNR5 may play an important role in enamel and dentin formation, probably through cell-cell and/or cell-matrix interactions.

Ameloblasts↗

Lactosylceramide is essential for the osteoclastogenesis mediated by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand.

Glycosphingolipids and their metabolites play important roles in a variety of biological processes. Several signal molecules are localized in a glycolipid-enriched microdomain on the cell surface, and their signals are regulated by the glycolipid composition. However, the function of glycolipids in osteoclastogenesis has not been clearly understood. We found that D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), a glucosylceramide synthase inhibitor, completely inhibits the osteoclast formation induced by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand (RANKL) in a dose-dependent manner. Expression of RANK, the receptor of RANKL, induced by macrophage colony-stimulating factor, was reduced markedly in D-PDMP-treated cells. d-PDMP also inhibited the phosphorylation of the inhibitor of nuclear factor-kappa B and extracellular signal-regulated kinase 1/2 induced by RANKL. In several experiments with the addition of glycolipids to D-PDMP-treated purified bone marrow cells, lactosylceramide (LacCer) strongly affected the differentiation into tartrate-resistant acid phosphatase mononucleated cells, but not positive multinucleated cells. GM3 and GM1 also recovered, but less effectively compared with LacCer. Moreover, exogenous LacCer recovered the reduced expression of RANK and the phosphorylation of inhibitor of NF-kappa B and extracellular signal-regulated kinase 1/2 after stimulation by RANKL at the same level of cells without D-PDMP treatment. Our data suggest that glycosphingolipids, especially LacCer, are necessary for the initiation step of RANKL-induced osteoclastogenesis.

Animals↗

FK506 promotes liver regeneration by suppressing natural killer cell activity.

We examined the mechanism of promotion of liver regeneration by tacrolimus hydrate (FK506), a potent immunosuppressant, after partial hepatectomy. The administration of FK506 significantly increased the bromodeoxyuridine (BrdU) labelling index at 36 and 48 h after 70% hepatectomy compared with the placebo group. Using the same model, we examined the effect of FK506 on the expression of hepatocyte growth factor (HGF) and transforming growth factor-beta 1 (TGF-beta 1) and found no changes in HGF and TGF-beta 1 mRNA expression in the liver or in the HGF protein concentration in plasma. We found that pretreatment with FK506 markedly reduced the activity and number of liver-resident natural killer (NK) cells at the time of partial hepatectomy. Our observations suggest that the promotion of liver regeneration by FK506 may be attributable to a reduction in the number of liver-resident NK cells and to inhibition of their activity.

Animals↗