Ikuo Nasu

Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss.

Osteoclasts are bone-specific multinucleated cells generated by the differentiation of monocyte/macrophage lineage precursors. Regulation of osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone-lytic diseases. Periodontitis is an inflammatory disease characterized by extensive bone resorption. In this study, we investigated the effects of sodium fluoride (NaF) on osteoclastogenesis induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. NaF strongly inhibited the P. gingivalis-induced alveolar bone loss. That effect was accompanied by decreased levels of cathepsin K, interleukin (IL)-1β, matrix metalloproteinase 9 (MMP9), and tartrate-resistant acid phosphatase, which were up-regulated during P. gingivalis-induced osteoclastogenesis. Consistent with the in vivo anti-osteoclastogenic effect, NaF inhibited osteoclast formation caused by the differentiation factor RANKL (receptor activator of nuclear factor κB ligand) and macrophage colony-stimulating factor (M-CSF). The RANKL-stimulated induction of the transcription factor nuclear factor of activated T cells (NFAT) c1 was also abrogated by NaF. Taken together, our data demonstrate that NaF inhibits RANKL-induced osteoclastogenesis by reducing the induction of NFATc1, ultimately leading to the suppressed expression of cathepsin K and MMP9. The in vivo effect of NaF on the inhibition of P. gingivalis-induced osteoclastogenesis strengthens the potential usefulness of NaF for treating periodontal diseases.

Association of natural tooth loss with genetic variation at the human matrix Gla protein locus in elderly women

AbstractNatural tooth loss represents a major medical issue within the elderly population, since it impairs masticatory function critical for oral intake of essential nutrition. Contribution of genetic factors has been implicated in the determination of natural tooth loss; degree of reduction in number of natural teeth remaining intact (NTI) varies among individuals; thus, heterogeneity in NTI might reflect genetic variation within the population. One candidate gene, the matrix Gla protein gene (MGP), has been implicated in the pathogenesis of bone loss through a repression of bone/tooth formation. We have investigated a possible association between the CA repeat polymorphism at the humanMGP gene locus and the NTI in 458 elderly Japanese women. In 916 chromosomes tested, ten alleles of the polymorphic nucleotide repeat were observed (designated A1-A10), among which five alleles were regarded as major alleles to be tested for the association. Twenty-seven women who possessed an A6 allele (164 bp) had significantly higher NTI than the remaining participants (n=431), who did not carry an allele of that size (mean: 10.0 teeth vs 5.6 teeth; P=0.007, Mann-Whitney test). An eight-year longitudinal follow-up study of NTI suggested that the genetic variations at the MGP locus did not affect the rate of tooth loss in the elderly period. These results suggest that genetic variation at the MGP gene locus is associated with some determinants for tooth loss in elderly women.

Evaluation of the Proportion of Cariogenic Bacteria Associated with Dental Caries

Background: Public oral health surveys have shown that the prevalence of dental caries in adults is increasing worldwide, resulting in increased workload and costs of dental and other clinical oral health services. Total streptococci are broadly grouped into mutans streptococci and three other species. They constitute a majority of bacteria found in the mouth. Of the total streptococci, the group of bacteria that primarily causes dental caries is mutans streptococci, which consists of seven species. Streptococcus mutans (S. mutans) is the mutans streptococcus most strongly associated with dental caries. To date, no simple assay (kit) has been developed for detecting S. mutans using plaque samples for caries risk assessment. This study aimed to evaluate the association between S. mutans and dental caries in adults based on the number and proportion of cariogenic bacteria in toothbrush plaque samples by culture methods to obtain basic data to develop clinical and chairside culture assay for caries risk assessment. Materials and Methods: Plaque samples from 164 adult volunteers were obtained using sterile toothbrushes. The ratio of S. mutans to total streptococci (Sm/TS ratio) was determined by counting the number of colonies by culture methods. The extent of dental caries and the relative risk based on bacterial counts were assessed. Results: The differences between Sm/TS ratios (%) in caries-free, medium-caries, and caries-active groups were statistically significant (p<0.001). The difference in the number of decayed, missing, and filled teeth (DMFT) in the four risk groups, each defined by Sm/TS ratio (%), was statistically significant (p<0.01). The risk associated with Sm/TS ratio was more significantly associated with the number of DMFT than with the number of S. mutans, and this parameter was useful in the selection of high-risk dental caries subjects. Conclusions: The results of the present study suggested a significant association between the levels of S. mutans and dental caries using dental plaque samples in adults and indicate that quantification of Sm/TS ratio is effective for detecting subjects with the severity of dental caries. This approach has the potential for previous study of the development of simple culture assay for a risk assessment that may be incorporated into future clinical or epidemiological studies measures for the improvement of oral health wor ldwide.

Evaluation of Dental Caries and Concomitant Infection Based on the Ratio of Cariogenic Bacteria using Plaque Samples in Adults

Background: The aim of this study was to evaluate the association between dental caries and concomitant infections of Streptococcus mutans (S. mutans) and Streptococcus sobrinus (S. sobrinus) according to the ratio of cariogenic bacteria in plaque samples from adults to obtain basic data to develop clinical and chairside culture assay (kits) for assessment of dental caries risk. Methods and Materials: Plaque samples from 192 adult volunteers (age range, 20-28 years) were obtained using sterile toothbrushes. Caries history and the number of decayed, missing, and filled (DMF) teeth were determined. Subjects were divided into high- and low-risk groups according to the ratio of S. mutans to total streptococci (Sm/TS ratio) and the number of S. mutans. Results: The numbers of S. mutans and S. sobrinus and the Sm/TS ratio were significantly greater in the cariesactive (CA) group than in the caries-free (CF) group. The number of bacteria and the Sm/TS ratio for the high-risk S. mutans plus detectable S. sobrinus subgroup was significantly greater in the CA group than in the CF group. High levels of S. mutans and S. sobrinus were significantly associated with dental caries. A significantly high caries risk was found between DMF teeth and the Sm/TS ratio for S. mutans when S. sobrinus was detected. Conclusions: The number of dental caries was greater in adults with plaque samples concomitantly infected with high levels of S. mutans and S. sobrinus than in those with a single infection. These findings indicate the usefulness of analysis of cariogenic dental bacteria to detect adult populations with the severity of dental caries according to the Sm/TS ratio using dental plaque samples.

Power Spectrum Analysis of Urinary Fluoride Excretion in Human Adults

Abstract The power spectrum analysis of the rhythm obtained from a study in which 6 healthy adults were fed a space food 3 times a day for 6 days is reported here. Urine samples were collected every 4 hours for determination of fluoride. The results were used for the calculation of the autocorrelation coefficient and power spectrum. The experimental data indicate that the rhythm exhibited by urinary fluoride excretion consisted of a 24-hour main cycle with minor peaks at 6, 8, and 12 hours. The data suggest periodicities in urine volume and 4 and 6 hour feeding cycles of adult subjects.