ピエゾ型機械受容チャネル1による歯の発生過程におけるWNTシグナルと一次繊毛発現の調整

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

ピエゾ型機械受容イオンチャネル1は間葉系幹細胞の分化運命決定の調節因子として機能する

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

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

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

COMBINATION OF IONS PROMOTES GINGIVAL FIBROBLAST MIGRATION

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

A case report of posttraumatic growth from a psychosomatic disorder due to traumatic stress in a 50s woman

【目的】本研究では，トラウマ性ストレスによる心身障害を抱えた50代女性に対する，トラウマ体験を物語ることに焦点を当てた介入の症例から心的外傷後成長（Posttraumatic growth: PTG）の生起過程を考察する。【現病歴】a 市における自然災害死目撃を機に不安，恐怖が持続。薬物治療で回復に向かうも，a 市に帰郷すると体調が増悪するというサイクルを繰り返した。【事例の経過】トラウマ体験を物語ることを目的に，ナラティブ・エクスポージャー・セラピー（Narrative Exposure Therapy: NET）を実施した結果，不安と恐怖が軽減した。その過程の中で夫との親密さが増し，ともにトラウマに立ち向かった結果，症状なくa 市に帰郷できるようになった。【考察】トラウマ体験を物語ることで，PTG に必要な「意図的反芻」，「語りの発展」，「スキーマの変化」を促進し「人間としての強さ」，「他者との関係」の領域においてPTG が生起したと考えられる。【Purpose】 This clinical study is to report the effectiveness of narrative approach for PTG to open up traumatic experiences in a 50s women with psychosomatic disorder due to traumatic stress.【History of present illness】 I anxiety and fear continued after witnessing the death of a natural disaster in a city. The patient recovered with medication. However, she repeated the cycle that his physical condition got worse when he returned to a city.【Progress】 As she described her traumatic experience, her anxiety and fear lessened. In the process, the intimacy with the husband increased, and they faced the trauma together. Two years after intervention, She was back to a city without symptoms.【Disccusion】 It is considered that “intentional rumination”, “development of the narrative”, and “change of the schema”necessary for PTG were promoted by telling the traumatic experience, and PTG arose in the region of “strength as a human” and “relation with others

Lavender Oil Reduces Depressive Mood in Healthy Individuals and Enhances the Activity of Single Oxytocin Neurons of the Hypothalamus Isolated from Mice: A Preliminary Study

Background. The aim of the present study was to assess the effects of lavender oil inhalation on blood pressure, pulse measurements, cortisol levels, depressive mood, and anxiety in healthy male adults. The mechanism was investigated by the action on oxytocin single neurons in the hypothalamus of rodents. Methods. The participants (n = 7) were aged 20–40 years. After randomisation, they received an inhaled dose of lavender oil or distilled water for 20 min. They received the other treatment after a washout period of one week. We assessed the outcomes using the Self-Rating Depression Scale, State-Trait Anxiety Inventory, and self-rated unidimensional Visual Analogue Scale for depression; anxiety; and hunger, thirst, and appetite, respectively. Blood pressure, pulse rate, and cortisol concentration in the peripheral blood were assessed before and after inhalation. In the rodent study (n = 4), oxytocin single neurons were isolated from the mouse hypothalamus. Intracellular Ca2+ concentration in the oxytocin neurons isolated from the hypothalamus was measured following direct administration of lavender oil. Results. Seven participants completed the study. Lavender inhalation decreased Self-Rating Depression Scale score and systolic and diastolic blood pressure. Ex vivo administration of lavender oil increased intracellular Ca2+ concentration in the hypothalamic oxytocin neurons. Conclusions. Lavender oil might be a useful therapy for stress relief, and its mechanism of action may include activation of the central oxytocin neurons