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en: Iroquois homeobox 3 regulates odontoblast proliferation and differentiation mediated by Wnt5a expression.

en: Iroquois homeobox (Irx) genes are TALE-class homeobox genes that are evolutionarily conserved across species and have multiple critical cellular functions in fundamental tissue development processes. Previous studies have shown that Irxs genes are expressed during tooth development. However, the precise roles of genes in teeth remain unclear. Here, we demonstrated for the first time that Irx3 is an essential molecule for the proliferation and differentiation of odontoblasts. Using cDNA synthesized from postnatal day 1 (P1) tooth germs, we examined the expression of all Irx genes (Irx1-Irx6) by RT-PCR and found that all genes except Irx4 were expressed in the tooth tissue. Irx1-Irx3 a were expressed in the dental epithelial cell line M3H1 cells, while Irx3 and Irx5 were expressed in the dental mesenchymal cell line mDP cells. Only Irx3 was expressed in both undifferentiated cell lines. Immunostaining also revealed the presence of IRX3 in the dental epithelial cells and mesenchymal condensation. Inhibition of endogenous Irx3 by siRNA blocks the proliferation and differentiation of mDP cells. Wnt3a, Wnt5a, and Bmp4 are factors involved in odontoblast differentiation and were highly expressed in mDP cells by quantitative PCR analysis. Interestingly, the expression of Wnt5a (but not Wnt3a or Bmp4) was suppressed by Irx3 siRNA. These results suggest that Irx3 plays an essential role in part through the regulation of Wnt5a expression during odontoblast proliferation and differentiation.

en: Biochemical and Biophysical Research Communications


en: 当科における5年間の障害児・有病児の初診時実態調査

ja: 当科における5年間の障害児・有病児の初診時実態調査

en: 障害児や有病児への理解の深まりから社会環境や福祉制度の整備が進みつつあるが，障害や全身疾患をもつ児が地域において疾病予防も含めた歯科医療を受けられる環境がいまだ十分にあるとは言えず，実情に応じた環境整備が求められる．そこで，今回，平成25年度から平成29年度に当科を受診した児のうち障害児・有病児の5年間の初診時実態調査を行い，過去に当科で行った調査と比較し，近年の変化を検討した．初診患者1,301名のうち，障害児・有病児の割合は49

en: The Japanese Journal of Pediatric Dentistry

ja: 小児歯科学雑誌


en: Fibroblast growth factor 2 suppresses the expression of C-C motif chemokine 11 through the c-Jun N-terminal kinase pathway in human dental pulp-derived mesenchymal stem cells

en: The regulation of the mesenchymal stem cell (MSC) programming mechanism promises great success in regenerative medicine. Tissue regeneration has been associated not only with the differentiation of MSCs, but also with the microenvironment of the stem cell niche that involves various cytokines and immune cells in the tissue regeneration site. In the present study, fibroblast growth factor 2 (FGF2), the principal growth factor for tooth development, dental pulp homeostasis and dentin repair, was reported to affect the expression of cytokines in human dental pulp-derived MSCs. FGF2 significantly inhibited the expression of chemokine C-C motif ligand 11 (CCL11) in a time- and dose-dependent manner in the SDP11 human dental pulp-derived MSC line. This inhibition was diminished following treatment with the AZD4547 FGF receptor (FGFR) inhibitor, indicating that FGF2 negatively regulated the expression of CCL11 in SDP11 cells. Furthermore, FGF2 activated the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNK) in SDP11 cells. The mechanism of the FGFR-downstream signaling pathway was then studied using the SB203580, U0126 and SP600125 inhibitors for p38 MAPK, ERK1/2, and JNK, respectively. Interestingly, only treatment with SP600125 blocked the FGF2-mediated suppression of CCL11. The present results suggested that FGF2 regulated the expression of cytokines and suppressed the expression of CCL11 via the JNK signaling pathway in human dental pulp-derived MSCs. The present findings could provide important insights into the association of FGF2 and CCL11 in dental tissue regeneration therapy.

en: Experimental and Therapeutic Medicine

ja: Experimental and Therapeutic Medicine


en: A Questionnaire Survey on the Guideline for Pediatric Dentistry in the National Dentistry Examination

ja: 歯科医師国家試験出題基準に対する日本小児歯科学会としての考え方


en: Survey of the Actual State of New Patients at the Pediatric Dentistry Department of Tokushima University Hospital between 1989 and 2018

ja: 当科における初診患者の実態調査∼平成における30年間の変遷∼

en:
The Heisei Era ended at the end of April 2019 and the Reiwa Era began.

For about 30 years in the Heisei era after the Showa era, the environment surrounding children changed rapidly, including the economic downturn, the acceleration of late marriage and declining birthrate, and progress in information and communication technology. As a result, individual households have diversified and a large polarization has become apparent. As pediatric dentists, we need to deal with and support children with all kinds of problems. Therefore, to clarify the transition of the first-visit patients in our clinic, we categorized the 30 years from 1989 to 2018 by five-year groups: early (1989-1993), middle (1997-2001) and late (2013-2018) stages, with a total of 5,892 patients, and then investigated and analyzed their properties. As a result, the number of new patients decreased from 2,477 in the early stage to 1,301 in the late stage. The male-female ratio was approximately 1:1 in each period. As for age, school age was the highest at about 40%, and there was no significant change in the age composition in each period. The most common chief complaint during each period was tooth decay, but it decreased from 44% in the early stage to 27% in the late stage. The proportion of children who brought a letter of referral increased from 23% in the early stage to 83% in the late stage, and the proportion of children with disabilities and illness increased from 13.8% in the early stage to 33% in the late stage. Compared to the early days, the chief complaints have diversified, and it has become clear that the functional differentiation of general dental clinics and university hospitals is progressing. Furthermore, it was suggested that the importance of medical and dental cooperation will increase in the future.

ja:
2019年4月末日をもって平成時代が終わり，令和時代が幕を開けた．平成の約30年間は経済成長の低迷，晩婚化・少子化の加速，一方で高度化する情報通信技術等，小児を取り巻く環境は，昭和時代から急速に変化しさまざまな領域で二極化が顕在化してきた側面もある．われわれ小児歯科医は，社会環境・家庭環境などの変化が子供の発育に及ぼす影響や問題を的確に読み取り，対応と支援を考えなければならない．そこで，平成元年から平成30年を初期(平成元年度∼5年度)，中期(平成9年度∼13年度)，後期(平成25年度∼29年度)の各5年間で区切り，15年間の計5,982人を対象に当科に来院した初診患者の調査・分析を行った．

その結果，初診患者数は，年少人口の減少に伴い初期2,477人から後期1,301人と減少した．男女比は，各時期ともに概ね1:1であった．年齢は，いずれも学童期が約40%と最も多く，年齢構成に大きな変化はみられなかった．主訴は，各時期ともに齲蝕が最も多いが，初期の44%から後期には27%と減少した．紹介状を持参した児の割合は，初期の23%から後期は83.3%に増加し，障害児・有病児の割合が初期13.8%から後期33%に増加した．初期に比べ，主訴は多様化し，かかりつけ歯科医院と大学病院の機能分化が進んでいることが明らかとなった．今後は，さらに医科歯科連携の重要性が高まることが示唆された．


en: Coordination of WNT signaling and ciliogenesis during odontogenesis by piezo type mechanosensitive ion channel component 1

en: Signal transmission from the mechanical forces to the various intracellular activities is a fundamental process during tissue development. Despite their critical role, the mechanism of mechanical forces in the biological process is poorly understood. In this study, we demonstrated that in the response to hydrostatic pressure (HP), the piezo type mechanosensitive ion channel component 1 (PIEZO1) is a primary mechanosensing receptor for odontoblast differentiation through coordination of the WNT expression and ciliogenesis. In stem cells from human exfoliated deciduous teeth (SHED), HP significantly promoted calcium deposition as well as the expression of odontogenic marker genes, PANX3 and DSPP, and WNT related-genes including WNT5b and WNT16, whereas HP inhibited cell proliferation and enhanced primary cilia expression. WNT signaling inhibitor XAV939 and primary cilia inhibitor chloral hydrate blocked the HP-induced calcium deposition. The PIEZO1 activator Yoda1 inhibited cell proliferation but induced ciliogenesis and WNT16 expression. Interestingly, HP and Yoda1 promoted nuclear translocation of RUNX2, whereas siRNA-mediated silencing of PIEZO1 decreased HP-induced nuclear translocation of RUNX2. Taken together, these results suggest that PIEZO1 functions as a mechanotransducer that connects HP signal to the intracellular signalings during odontoblast differentiation.

en: Scientific Reports

ja: Scientific Reports


en: Combination of ions promotes cell migration via extracellular signalregulated kinase 1/2 signaling pathway in human gingival fibroblasts.

en: Wound healing is a dynamic process that involves highly coordinated cellular events, including proliferation and migration. Oral gingival fibroblasts serve a central role in maintaining oral mucosa homeostasis, and their functions include the coordination of physiological tissue repair. Recently, surface pre-reacted glass-ionomer (S-PRG) fillers have been widely applied in the field of dental materials for the prevention of dental caries, due to an excellent ability to release fluoride (F). In addition to F, S-PRG fillers are known to release several types of ions, including aluminum (Al), boron (B), sodium (Na), silicon (Si) and strontium (Sr). However, the influence of these ions on gingival fibroblasts remains unknown. The aim of the present study was to examine the effect of various concentrations of an S-PRG filler eluate on the growth and migration of gingival fibroblasts. The human gingival fibroblast cell line HGF-1 was treated with various dilutions of an eluent solution of S-PRG, which contained 32.0 ppm Al, 1,488.6 ppm B, 505.0 ppm Na, 12.9 ppm Si, 156.5 ppm Sr and 136.5 ppm F. Treatment with eluate at a dilution of 1:10,000 was observed to significantly promote the migration of HGF-1 cells. In addition, the current study evaluated the mechanism underlying the mediated cell migration by the S-PRG solution and revealed that it activated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), but not of p38. Furthermore, treatment with a MEK inhibitor blocked the cell migration induced by the solution. Taken together, these results suggest that S-PRG fillers can stimulate HGF-1 cell migration via the ERK1/2 signaling pathway, indicating that a dental material containing this type of filler is useful for oral mucosa homeostasis and wound healing.

en: Molecular Medicine Reports

ja: Molecular Medicine Reports


en: Additional Maxillary Primary Central Incisor Root Causing Disturbance of Permanent Tooth Eruption:Case Report

ja: 2根2根管性上顎乳中切歯の存在により後継永久歯の萌出遅延がみられた1例

en: Teeth with a supernumerary root, such as a double, additional, extra, or accessory root, or multiple roots, are a deviation from the general form. A supernumerary root can occur in nearly all types of permanent teeth, while it is extremely rare in deciduous teeth. In Japan, there are only a few clinical reports of such an occurrence in maxillary and mandible primary canines, or maxillary second and mandibular primary molars, while clinical reports of a maxillary primary central incisor with a supernumerary root are available. Here, we report a case of a maxillary primary central incisor with an additional root that caused disturbance of permanent tooth eruption.

ja:
過剰根とは，一般的な形態から逸脱した歯(奇形歯)の一種であり，複根や副根を有した歯根をいう1)．永久歯ではほとんどすべての歯種において過剰根を認めることは知られているが，乳歯において過剰根を認めることは極めて稀とされている．国内の過去の報告例においても，上下顎乳犬歯，上顎第2乳臼歯，下顎第2乳臼歯の臨床報告が数例あるのみで，上顎乳中切歯での報告はない．

今回われわれは，上顎左側乳中切歯において2根2根管を有し，後継永久歯の萌出障害の一因となったと考えられた1例を経験したのでその概要を報告する．


en: Association Between Dental Caries and Lifestyle in Children

ja: 齲蝕罹患と生活習慣の相関とその解決課題

en: The prevalence of dental caries is low in younger children, while rapid progression occurs in adolescence. The purpose of this study was to clarify the association of prevalence of dental caries in children and daily lifestyle habits. A total of 100 children (57 boys, 43 girls, average age 4 years 6 months) who visited our department were enrolled and divided into the caries and non-caries group. Each parent or guardian was asked regarding the daily lifestyle of the child, including nutrition and oral health. We found that "maternal employment", "bedtime", and "frequent snacks" were correlated with dental caries prevalence. There was no significant differences in regard to "living with grandparents","presence of brothers and/or sisters", "wake-up time", and "knowledge of dental health". Furthermore, we found that all children with caries ate excessively during meals, excluding snacks. Dental health promotion contributes to specifically target dental caries, while establishment of healthy lifestyle habits in children, particularly healthy habits for eating, is important.

ja: 小児期の齲蝕は統計学上経年的に減少傾向を示しているが，学童期を過ぎ成人期に至る過程で急速に口腔内の健康状態が悪化していく．このことは歯科健康管理が他律期においては優れた成果を挙げてきたものの，子供達における健康の自律獲得支援の面では課題が存在することを示唆している．そこで今回，歯科疾患と生活習慣との関連について調査を行った．被験者は男児57名，女児43名(平均年齢4歳6か月，そのうち齲蝕あり57名，齲蝕なし43名)の100名を対象とした．被験者に対し家庭環境，基本的な生活習慣，歯科に関する事項，食生活習慣に関する調査を行ったところ，母親の就労ありの群および就寝時間が22時以降の群で齲蝕罹患が有意に多かった．祖父母の同居，きょうだいの有無，起床時間，齲蝕予防法に関する知識，歯みがきの回数，フッ化物の使用経験，かかりつけ歯科医の有無に関しては，有意差はみられなかった．さらに，齲蝕ありの群では甘味摂取の回数が有意に多く，かつすべての齲蝕ありの児が1日の推定エネルギー必要量(kcal/日)を超えたエネルギー量を摂取していた．さらに，1日に摂取した総エネルギー量から甘味による摂取エネルギー量を差し引いても，齲蝕ありの群では3回の食事だけですでに1日の推定エネルギー必要量を超えていることが明らかになった．子供を取り巻く環境の変化の中で，とりわけ味覚や食事に対する考え方など食行動の基本が形成される小児期に過栄養や偏った甘味優位な栄養習慣が歯科保健の自律獲得の過程に影響を及ぼしているのではないかと考えられた．


en: A study on the effect of Oral Myofunctional Therapy (MFT) in children

ja: 小児における口腔筋機能療法(MFT)の訓練効果について

en: Oral myofunctional therapy (MFT) is a specialized training technique taught to patients for selftreatment of a variety of oral muscle functional disorders and habit patterns that disrupt normal oral and dental development. Although various training methods have been proposed, there are few reports on the effects of training in individual subjects. The purpose of this study was to clarify the effects of various MFT methods in 20 children (15 boys, 5 girls : average age 7 years 7 months) who underwent training at our hospital. The results revealed that the percentage of children with poor lip seal improved from 55% to 33%,while tongue thrust during swallowing and articulating improved from 100% to 50% and 95% to 60% respectively. We also found that "Water Slurp Swallow" training significantly contributed to improved tongue thrust during swallowing. However, even though the subjects were able to master the training methods, they failed to obtain correct oral functions, thus new training methods as well as the timing for starting training must be considered. Oral function is regarded as important throughout life, with childhood a crucial stage for establishing a healthy foundation. Our results also showed that 20% of the child subjects had oral functional difficulties without morphological problems, indicating that both morphological and functional problems should be evaluated. MFT is an effective method for support of oral function and development.

ja: 口腔筋機機能療法(Oral Myofunctional Therapy : MFT，以下MFT)は口腔周囲筋のバランスの調和をとることで，歯列・咬合の形態を正常に維持することや，咀嚼・嚥下・構音といった小児期の口腔機能の発達支援を目的として行われる治療法の1 つである．様々な訓練方法が提案されているが，個々の訓練の効果について検討された報告は少ない．そこで，今回当科で実施したMFT について一連の訓練を行い，かつ発表に際して同意の得られた20 名(男児15 名，女児5 名，平均年齢7 歳7 か月)についてその治療効果の検討を行った． その結果，訓練前・後で比較して口唇閉鎖不全のある児は55%から35%，嚥下時舌突出のある児は100 %から50%，構音時舌突出のある児は95%から60%に減少し，改善がみられた．とくに嚥下時舌突出と訓練法の1 つである「スラープスワロー」との間に相関を認めた．しかし，訓練が達成できていても機能の改善が十分でない児もおり，さらなる訓練法や訓練時期の検討が必要であると考えられた． 様々な分野で口腔機能が注目されているが，とりわけ小児期での口腔機能の獲得は生涯を通じての健康に非常に重要な意味をもつ．本調査では20%の児は形態的な問題を有しておらず機能面の問題のみを呈していた．こうした児についても積極的に介入し口腔機能を向上させることは将来の健康寿命延伸に有意義である．そのため，小児の発育・発達に沿った訓練を構築し，口腔機能獲得の支援法として提案することが必要である．

en: The Japanese Journal of Pediatric Dentistry


en: Piezo type mechanosensitive ion channel component 1 functions as a regulator of the cell fate determination of mesenchymal stem cells

en: The extracellular environment regulates the dynamic behaviors of cells. However, the effects of hydrostatic pressure (HP) on cell fate determination of mesenchymal stem cells (MSCs) are not clearly understood. Here, we established a cell culture chamber to control HP. Using this system, we found that the promotion of osteogenic differentiation by HP is depend on bone morphogenetic protein 2 (BMP2) expression regulated by Piezo type mechanosensitive ion channel component 1 (PIEZO1) in MSCs. The PIEZO1 was expressed and induced after HP loading in primary MSCs and MSC lines, UE7T-13 and SDP11. HP and Yoda1, an activator of PIEZO1, promoted BMP2 expression and osteoblast differentiation, whereas inhibits adipocyte differentiation. Conversely, PIEZO1 inhibition reduced osteoblast differentiation and BMP2 expression. Furthermore, Blocking of BMP2 function by noggin inhibits HP induced osteogenic maker genes expression. In addition, in an in vivo model of medaka with HP loading, HP promoted caudal fin ray development whereas inhibition of piezo1 using GsMTx4 suppressed its development. Thus, our results suggested that PIEZO1 is responsible for HP and could functions as a factor for cell fate determination of MSCs by regulating BMP2 expression.


en: Disaster Prevention for Children and Adults with Disabilities

ja: 災害時要援護者である小児および障碍児・者を持つ保護者の防災意識に関する調査


en: Recruitment of mesenchymal stem cells by stromal cell-derived factor 1 in pulp cells from deciduous teeth

en: Dental pulp cells (DPCs), including dental pulp (DP) stem cells, play a role in dentine repair under certain conditions caused by bacterial infections associated with caries, tooth fracture and injury. Mesenchymal stem cells (MSCs) have also been shown to be involved in this process of repair. However, the mechanisms through which MSCs are recruited to the DP have not yet been elucidated. Therefore, the aim of the present in vitro study was to investigate whether stromal cell-derived factor 1 (SDF1)-C-X-C chemokine receptor type 4 (CXCR4) signaling is involved in tissue repair in the DP of deciduous teeth. A single-cell clone from DPCs (SDP11) and UE7T-13 cells were used as pulp cells and MSCs, respectively. The MG-63 and HuO9 cells, two osteosarcoma cell lines, were used as positive control cells. Reverse transcription polymerase chain reaction (RT-PCR) revealed that all cell lines (SDP11, UE7T-13 MG-63 and HuO9) were positive for both SDF1 and CXCR4 mRNA expression. Moreover, immunocytochemical analysis indicated that SDF1 and CXCR4 proteins were expressed in the SDP11 and UE7T-13 cells. SDF1 was also detected in the cell lysates (CLs) and conditioned medium (CM) collected from the SDP11 and UE7T-13 cells, and AMD3100, a specific antagonist of CXCR4, inhibited the migration of the UE7T-13 cells; this migration was induced by treatment with CM, which was collected from the SDP11 cells. In addition, real-time PCR showed that the expression of SDF1 in the SDP11 cells was inhibited by treatment with 20 ng/ml fibroblast growth factor (FGF)-2, and exposure to AZD4547, an inhibitor of the FGF receptor, blocked this inhibition. Collectively, these data suggest that SDF1 produced by DP plays an important role in homeostasis, repair and regeneration via the recruitment of MSCs.

en: International Journal of Molecular Medicine


en: Dental findings and management in a child with hypomelanosis of Ito

en: Pediatric Dental Journal

ja: Pediatric Dental Journal


en: Capillary Hemangioma on Palate of Infant:Case Report

ja: 幼児期の小児の口蓋に発生した血管腫の1例

en: A hemangioma frequently occurs on the tongue, lip, buccal mucosa, and gingiva in the oral region,though it relatively rarely seen on the palate. We report a case of capillary hemangioma found on the palate of a 2-year-10-month-old boy. He was referred to our department with the chief complaint of a tumor on the palate and a hemangioma was noted on the palatal side of the upper deciduous incisors.We performed surgical resection and the mass was extirpated. The postoperative course was uneventful. Although there was no evidence of recurrence at 6 months after surgery, careful follow-up examinations will be necessary until the upper permanent incisors erupt.

ja: 血管腫は血管の増殖を特徴とする良性腫瘍であり，小児の顎口腔領域における良性腫瘍のなかでは比較的多く，軟組織腫瘍の中で最も多い．顎口腔領域に発生する本腫瘍は舌，口唇，歯肉，頬粘膜に好発し，口蓋に発生することは稀である．今回，われわれは，2 歳10 か月男児の口蓋に発生した血管腫を経験したので，その概要を報告する．患児は初診の約4 か月前に下顎部を打撲したため近医歯科を受診した．その際，上顎両側乳中切歯口蓋側歯肉の腫瘤を指摘され，単純性歯肉炎の診断下にプラークコントロールを受けていたが改善しないため当科を紹介された．初診時，切歯乳頭から上顎両側乳中切歯口蓋側歯肉にかけて大きさ10×8×5mm類円形で境界明瞭，暗赤色，表面不整，弾性軟の腫瘤を認め，上顎腫瘍と診断した．局所麻酔下に腫瘍切除術を施行した．病理組織学的診断は毛細血管腫であった．今後，再発に注意しながら，少なくとも永久歯交換まで厳重な経過観察が必要と考えられた．


en: Forced mastication increases survival of adult neural stem cells in the hippocampal dentate gyrus.

en: In this study, we examined the effect of forced mastication on neurogenesis in the hippocampal dentate gyrus (DG) of adult mice. Six-week-old mice were subjected to either a hard or normal diet for 13 weeks. They received a daily injection of bromodeoxyuridine (BrdU) for 12 consecutive days beginning at 14 weeks of age. The number of BrdU-positive cells in the DG was counted 1 day after and 5 weeks after the final BrdU injection. The number of BrdU-positive cells 1 day after injection did not differ between the 2 diet groups. However, the number of BrdU-positive cells in the group fed the hard diet was significantly increased 5 weeks after BrdU injection compared to the group fed the normal diet. The results of the Morris water maze test showed that mice fed a hard diet required significantly less time to reach the platform than the control mice when tested at 10 days. Moreover, mice in the group fed the hard diet spent significantly more time in the former platform area than the group fed the normal diet, indicating that hard diet feeding improved spatial memory compared to normal diet feeding. Real-time PCR analysis showed that the expression of glutamate receptor 1 mRNA was significantly increased in the group fed the hard diet compared with the group fed the normal diet. These results suggest that mastication increases the survival of adult neural stem cells in the hippocampal DG.

ja: International Journal of Molecular Medicine


en: Many Congenital Missing Teeth in a Case of Bloch-Sulzberger Syndrome

ja: 色素失調症により多数歯欠損が認められた症例

en: Journal of the Japanese Society for Disability and Oral Health

ja: 障害者歯科