Influences of reduced masticatory sensory input from soft-diet feeding upon spatial memory/learning ability in mice.

It has been reported that reduction of masticatory afferent stimulation might influence learning and memory function. In order to clarify the influences of reduced masticatory sensory input on spatial memory/learning ability and neuropathological changes, we conducted the Morris water maze experiment and investigated the number of hippocampal neurons in association with the differences in masticatory afferent stimuli from hard- and soft-diet feeding in mice. The water maze experiment showed no significant difference in learning ability between 180-day-old solid- and powderdiet groups. Meanwhile, the ability was significantly reduced in the 360-day-old powder-diet group as compared with the age-matched solid-diet group. The total number of pyramidal cells in the hippocampal CA1 and CA3 regions was significantly smaller in 360-day-old powder-diet group than in the remaining groups. These results demonstrate that reduction of masticatory afferent stimuli due to long-term soft-diet feeding may induce neuron loss in the hippocampus and reduced memory/learning ability.

Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome.

Cancer-prone syndrome of premature chromatid separation (PCS syndrome) with mosaic variegated aneuploidy (MVA) is a rare autosomal recessive disorder characterized by growth retardation, microcephaly, childhood cancer, premature chromatid separation of all chromosomes, and mosaicism for various trisomies and monosomies. Biallelic BUB1B mutations were recently reported in five of eight families with MVA syndrome (probably identical to the PCS syndrome). We here describe molecular analysis of BUB1B (encoding BubR1) in seven Japanese families with the PCS syndrome. Monoallelic BUB1B mutations were found in all seven families studied: a single-base deletion (1833delT) in four families; and a splice site mutation, a nonsense mutation, and a missense mutation in one family each. Transcripts derived from the patients with the 1833delT mutation and the splice site mutation were significantly reduced, probably due to nonsense-mediated mRNA decay. No mutation was found in the second alleles in the seven families studied, but RT-PCR of BUB1B and Western blot analysis of BubR1 indicated a modest decrease of their transcripts. BubR1 in the cells from two patients showed both reduced protein expression and diminished kinetochore localization. Their expression level of p55cdc, a specific activator of anaphase-promoting complex, was normal but its kinetochore association was abolished. Microcell-mediated transfer of chromosome 15 (containing BUB1B) into the cells restored normal BubR1 levels, kinetochore localization of p55cdc, and the normal responses to colcemid treatment. These findings indicate the involvement of BubR1 in p55cdc-mediated mitotic checkpoint signaling, and suggest that >50% decrease in expression (or activity) of BubR1 is involved in the PCS syndrome.

Neutralizing effects of an anti-vascular endothelial growth factor antibody on tooth movement.

Our recent studies demonstrated that local administration of recombinant human vascular endothelial growth factor (rhVEGF) during experimental tooth movement enhanced the number of osteoclasts and the rate of tooth movement. The purpose of this study was to examine the effect of anti-VEGF polyclonal antibody on osteoclastic differentiation, the amount of tooth movement, and the degree of tooth relapse in 30-day-old mice. First, these mice were subjected to various doses of anti-VEGF polyclonal antibody, with tooth movement for three days. In the next study, daily injections of 10-microg antibody were administered for 18 days during the experimental tooth movement. The amount of tooth movement was measured as in our previous study. Furthermore, in the third study, we administered daily injection of 10-microg antibody and measured tooth relapse after the experimental tooth movement for 45 days. The osteoclasts number in 10- and 50-microg antibody two-time injection group was significantly smaller than that in the controls (P < .05). The number of osteoclasts was decreased more substantially by daily injection of 10-microg antibody, showing more significant differences from the controls (P < .01). The amount of tooth movement was significantly less in the experimental group than in the controls on days 15 and 18 (P < .05). Furthermore, the amount of relapse in the experimental group was significantly less than that in the controls on days 9 and 11 after removal of the appliance (P < .05). These results show that the treatment of anti-VEGF polyclonal antibody markedly reduced the osteoclasts number and inhibited the amount of tooth movement and relapse of moved teeth.

Guided bone regeneration to repair an alveolar bone defect in a girl whose cleft lip and palate had been repaired.

We report the case of a girl aged 10 years whose alveolar bony defect was closed with a polytetrafluoroethylene membrane, which was incorporated in bone after 4 months. We suggest that the principle of guided bone regeneration can be used to repair cleft defects provided that the mucoperiosteal flaps are handled carefully and that good anti-infective measures are taken to prevent early exposure and microbial contamination of the membrane barrier.

Bactericidal effects of acidic electrolyzed water on the dental unit waterline.

Many studies have been conducted in the United States regarding the microbial contamination of dental unit waterline, but not in Japan. Recently, acidic electrolyzed water has been used in the medical and dental fields. In this study, we investigated the bactericidal effects of the temporary inflow of acidic electrolyzed water on microbial contamination of the dental unit waterline. First, in order to observe the daily bacterial contamination of the dental unit waterline, water samples were collected at the end of handpieces and three-way syringes before the inflow of acidic electrolyzed water. They were cultured to detect viable bacteria. Later, the inflow of acidic electrolyzed water was conducted through the piping box of the dental unit. Before starting operation on next day, water samples were collected and cultured, as described above. The mean viable bacteria count was 910 -/+ 190 CFU/ml at the end of handpieces, and 521 -/+ 116 CFU/ml at the end of three-way syringes before the inflow of acidic electrolyzed water. However, bacteria were detected in only small numbers at the end of handpieces and three-way syringes on the next day. These results indicated that acidic electrolyzed water could be applied as an appropriate measure against bacterial contamination of the dental unit waterline.

Effect of alendronate on osteoclast differentiation and bone volume in transplanted bone.

Alendronate, one of the bisphosphonates, is known to have an inhibitory effect on bone resorption. The purpose of this study was to investigate the effects of alendronate on ectopic bone graft resorption and to determine the optimal dose in the mouse. The grafted bone in the control group disappeared due to resorption by osteoclasts within 5 weeks. In the experimental groups, the area of bone tissue decreased by only 20-40% at 5 weeks post-operatively. At 8 and 9 weeks after surgery, the decreased area of bone structure was significantly less in all the 10(-4) M injected alendronate-immersed groups than in the 10(-4) M non-injected alendronate-immersed. At 9 weeks after surgery, the number of osteoclasts were significantly less in the 10(-4) M injected alendronate-treated groups than in the 10(-4) M non-injected alendronate-treated groups. These results suggest that alendronate inhibits resorption of ectopic bone graft at concentrations of 10(-4) and 10(-6) M.

Amyloid beta protein deposition and neuron loss in osteopetrotic (op/op) mice.

Formation of senile plaques (SPs) by amyloid beta (Abeta) protein is a neuropathological change which characterizes Alzheimer's disease (AD), and Abeta deposition and neuron loss are essential for the pathological cascade of the disease. Although the mechanism of Abeta deposition remains unclear, it has been suggested that clearance of Abeta protein may be impaired in the AD brain. Previous studies demonstrated that microglia were able to remove Abeta by releasing a metalloprotease or by phagocytosis, suggesting that microglia may play an important role in preventing Abeta deposition in the central nervous system (CNS). On the other hand, it was reported that the number of microglia was reduced in osteopetrotic (op/op) toothless mice resulting from the lack of functional macrophage colony-stimulating factor (M-CSF). The present study was thus designed to examine the Abeta deposition and the number of hippocampal neurons in the brain of op/op mice. A number of fibrillar plaques were detected in the cerebral cortex, hippocampus, amygdala and hypothalamus in op/op mice, however, no quantitative evidence of Abeta deposition was observed in normal mice. Moreover, the total number of pyramidal cells in the hippocampal CA1, and CA3 regions was significantly reduced in op/op mice when compared to the controls. These results demonstrate that Abeta deposition influence neuron loss and it may be suspected that expression of SPs may be in part regulated by microglia under physiological conditions.

Effect of insulin-like growth factor-I (IGF-I) on femoral bone modeling in growing mice.

The time-dependent effects of daily dosing of IGF-I (1.21 mg/g) on the linear growth of the femur were investigated in mice. The femoral length and volume and the number of osteoclasts were significantly greater after IGF-I injection as compared to the non-injected control, suggesting that the IGF-I imbalance might cause a quick turnover cycle of the bone resulting in the altered femoral modeling.