Kazumune Arikawa

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.

Effects of coenzyme Q10 on salivary secretion

OBJECTIVES Dry mouth is a condition associated with reduced salivary secretion and is thought to be related to aging. This study was conducted to test whether reduced (ubiquinol) or oxidized (ubiquinone) forms of CoQ10 affect salivary secretion and salivary CoQ10 content before and after treatment. DESIGN AND METHODS Sixty-six patients were given either ubiquinol or ubiquinone orally at a dosage of 100 mg/day, or a placebo for 1 month, and salivary secretion and salivary CoQ10 content were analyzed before and after treatment. RESULTS Both parameters were significantly improved following treatment with either form of CoQ10, suggesting the effectiveness of CoQ10 in attenuating dry mouth symptoms. CONCLUSION CoQ10 was locally detected in salivary glands, suggesting that orally administered CoQ10 was transported to the salivary glands via the blood stream and exerted its activity, improving salivary secretion.

Micromolar Levels of Sodium Fluoride Promote Osteoblast Differentiation Through Runx2 Signaling.

Bone remodeling is a vital physiological process of healthy bone tissue in humans. Imbalances in this vital process lead to pathological conditions, including periodontal diseases. In this study, we characterized the effects of micromolar levels of NaF on the proliferation and osteogenic differentiation of MC3T3-E1 osteoblastic cells. NaF significantly enhanced the proliferation, alkaline phosphatase (ALP) activity, and mineralization of MC3T3-E1 cells. Quantitative real-time PCR analysis revealed that the expression of mRNAs encoding runt-related transcription factor 2 (Runx2), Osterix, Osteopontin and Osteocalcin was up-regulated in NaF-treated MC3T3-E1 cells compared with untreated controls. Western blot analysis demonstrated that Runx2 and Osterix were inhibited by Runx2 siRNA but were re-activated by treatment with NaF. Furthermore, in vivo evidence indicated that NaF protects against Porphyromonas gingivalis-induced periodontal inflammation and alveolar bone loss in a P. gingivalis-challenged experimental periodontitis animal model. These data suggest that NaF promotes the osteoblastic differentiation of MC3T3-E1 cells through the Runx2/Osterix pathway and may be effective for the treatment of bone-related disorders.

Possible pharmacotherapy for nifedipine‐induced gingival overgrowth: 18α‐glycyrrhetinic acid inhibits human gingival fibroblast growth

This investigation aimed to establish the basis of a pharmacotherapy for nifedipine‐induced gingival overgrowth. Gingival overgrowth has been attributed to the enhanced growth of gingival fibroblasts. In this study, we investigated the effects of 18‐α‐glycyrrhetinic acid (18α‐GA) on growth, the cell cycle, and apoptosis and on the regulators of these processes in gingival fibroblasts isolated from patients who presented with nifedipine‐induced gingival overgrowth.

The epigenetic regulation of CXCL14 plays a role in the pathobiology of oral cancers

Background: Chemokines selectively attract and activate leukocytes and play roles in a variety of homeostatic and disease processes. Explore the biological properties of CXCL14 seems complicated due to unknown functional characteristics of CXCL14 in cancer. Methods: To study the multistep process of oral cancer development, we analyzed oral samples spanning normalcy, dysplasia and cancer from multiple perspectives, revealing a cascade of progressive changes. Results: CXCL14 protein was expressed in the cytoplasm adjacent to tumors. T classification (P<0.001), clinical stage (P=0.0013) and nodal metastasis (P=0.0035) were significantly associated with CXCL14 in relationships between CXCL14 expression levels and tumor and patient characteristics. Compared with non-tumor tissue, expression of the epidermal growth factor receptor (EGFR) gene was increased in dysplasia and was further sustained in cancer. Our data show an inverse relationship between CXCL14 and EGFR expression levels in tumor cells indicating that CXCL14 expression is beneficial for tumor suppression. To explore epigenetic regulation and the impact of CXCL14 on oral cancer, analysis of CpG islands methylation in the CXCL14 promoter region indicated that the abnormal hypermethylation of that promoter region in tumor cells and tissues is one of the mechanisms causing the reduced expression. Restoration of CXCL14 expression was induced by treatment with 5-aza-2′-deoxycytidine. Using in vivo mouse models, we demonstrate that the restoration of CXCL14 expression in irradiation-induced oral carcinoma cells induces the expression of Late Cornified Envelope (LCE) genes. Conclusions: Our data suggest that LCE genes are a novel target of CXCL14 and are likely to have a tumor suppressor function through the modulation of CXCL14 expression. In conclusion, CXCL14 might play a pivotal role in the pathobiology of oral cancer, probably by regulating DNA methylation and leukocyte migration. The level of CXCL14 expression may be a valuable adjuvant parameter to predict the prognosis of patients with oral carcinoma and may be a potential therapeutic target.

Influence of aging on experimental gastrointestinal motility in extraction of rat molar teeth

Abstract The purpose of the present study was to determine whether different consistency of diet and malocclusion induced by the extraction of molar teeth on the masticatory organs modulated gastric acid secretion, gastric emptying and intestinal transit in young and elder rats. Male Wistar rats (young, 5weeks; elder, 1.5years) were used in this experiment, and were divided into 2 groups. Group one (G1) was maintained with solid diet, Group two (G2) with mud diet. Further, the mandibular molar teeth of G2 were extracted. The experimental period was 10weeks. The effect of aging and malocclusion on the parameters of gastric secretion was examined using pylorus-ligated rats. The gastric emptying rate (GER) and small intestinal transit rate was determined in rats by evans blue from the stomach and charcoal from the small intestinal, respectively. In pylorus-ligated rats, Young-G2 rat of gastric juice volume, acid output and pepsin secretion remarkably showed significant decrease in comparison with Young-G1 group, but there was not significant difference between Elder-G1 and Elder-G2. GER of Young-G2 rat group was 44.2±7.9%, significantly lower than that of Young-G1 rat group (61.6±8.8%, P