Allergic Oral Mucositis due to Musical Instrument Metal : A Case Report

金属アレルギーとは金属が皮膚や粘膜に接触し，その部位から溶出した金属イオンが体内に取り込まれることで起きるアレルギー反応である。今回われわれは，楽器のチューバのマウスピースによる金属アレルギーが原因と疑われる口腔粘膜炎を発症した1例を経験したのでその概要を報告する。 患児は10歳8か月女児。小学校の金管バンドクラブに所属して以降，歯肉の腫脹や口腔内の炎症所見を認めたため，近医にてパッチテストや血液検査を施行されるも金属アレルギーおよび自己免疫疾患は否定された。当科初診時には，唇頰側歯肉と頰粘膜に軽度自発痛ならびに発赤を伴う瀰漫性腫脹を認めた。歯肉は易出血性で，増殖し仮性ポケットが形成されていた。歯周病原細菌検査にて歯周病原細菌は基準値以下であった。歯肉増殖部位の病理組織検査は，歯肉炎の診断であり口腔衛生指導を徹底したが，症状の改善はみられなかった。ところが，楽器（チューバ）とマウスピースの変更を契機に口腔内の炎症が劇的に改善し，その1か月後には，健全な口腔粘膜の状態を呈していた。新旧のマウスピースを比較したところ，旧マウスピースではめっきが剥がれている箇所が多数みられた。金属組成分析ならびに金属パッチテスト検査を行ったところ，Crにアレルギーがある可能性が高いことが明らかとなり，金属アレルギーが原因で引き起こされた口腔粘膜炎と診断した。口腔内はマウスピースの変更以降，良好な状態が継続している。Metal allergy is an allergic reaction that occurs when metal touches the skin or mucous membranes, and eluted metal ions are taken into the body. Here we report a case of metal allergy caused by the mouthpiece of a musical instrument. The patient was a girl of 10 years and 8 months. Since joining the brass band club of her elementary school, gingival swelling and inflammation in the oral cavity had appeared. Therefore, a patch test and a blood test were performed by a local clinic, but both metal allergies and autoimmune diseases were denied. At the first visit to our hospital, the labial and buccal gingiva and buccal mucosa presented mild spontaneous pain and diffuse swelling with redness. The gingiva bled easily, and had grown over, forming false pockets. The periodontopathic bacteria were below reference values in the periodontopathic bacteria test. Histopathological examination revealed that the gingival overgrowth was periodontitis. Although we started to provide professional oral care, her condition did not improve. Eleven months later, the inflammation in the oral cavity drastically improved. We found that the musical instrument (tuba) had been changed to a new one. After that, the condition of the oral mucosa was healthy. The old mouthpieces had some spots where the plating had peeled off. Energy dispersive X-ray fluorescence spectrometry was carried out for an element analysis of the mouthpieces, and a metal patch test was also performed. The results showed that she may have had an allergic response to Cr. Finally, we diagnosed oral mucositis caused by metal allergies. The patient made steady progress after the mouthpiece was changed

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

FGF2 SUPPRESSED CCL11 EXPRESSION IN HUMAN DENTAL PULP-DERIVED MSCs

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

Pannexin3 regulates odontoblast proliferation and differentiation

Highly coordinated regulation of cell proliferation and differentiation contributes to the formation of functionally shaped and sized teeth; however, the mechanism underlying the switch from cell cycle exit to cell differentiation during odontogenesis is poorly understood. Recently, we identified pannexin 3 (Panx3) as a member of the pannexin gap junction protein family from tooth germs. The expression of Panx3 was predominately localized in preodontoblasts that arise from dental papilla cells and can differentiate into dentin-secreting odontoblasts. Panx3 also co-localized with p21, a cyclin-dependent kinase inhibitor protein, in preodontoblasts. Panx3 was expressed in primary dental mesenchymal cells and in the mDP dental mesenchymal cell line. Both Panx3 and p21 were induced during the differentiation of mDP cells. Overexpression of Panx3 in mDP cells reduced cell proliferation via upregulation of p21, but not of p27, and promoted the Bone morphogenetic protein 2 (BMP2)-induced phosphorylation of Smad1/5/8 and the expression of dentin sialophosphoprotein (Dspp), a marker of differentiated odontoblasts. Furthermore, Panx3 released intracellular ATP into the extracellular space through its hemichannel and induced the phosphorylation of AMP-activated protein kinase (AMPK). 5-Aminoimidazole-4-carboxamide-ribonucleoside (AICAR), an activator of AMPK, reduced mDP cell proliferation and induced p21 expression. Conversely, knockdown of endogenous Panx3 by siRNA inhibited AMPK phosphorylation, p21 expression, and the phosphorylation of Smad1/5/8 even in the presence of BMP2. Taken together, our results suggest that Panx3 modulates intracellular ATP levels, resulting in the inhibition of odontoblast proliferation through the AMPK/p21 signaling pathway and promotion of cell differentiation by the BMP/Smad signaling pathway

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

Prevention of Sports-related Dental Injuries in Children

A sports-related dental injury is defined as injuries to the oral and maxillofacial regions associated with sports activities, and involves tooth fracture and luxation, facial bone and temporomandibular fractures, and soft tissue injury. Participants in sports activities are always at risk for traumatic injury, with the oral and maxillofacial region often affected. Dental injuries also have a high rate of occurrence among sports-related injuries received during school physical education classes and club activities. Unfortunately, nearly all such dental injuries are irreversible, and the loss of teeth or their supporting tissues has a significant impact on the quality of life of affected individuals. Thus, for prevention of sports-related dental injuries, it is important for dental professionals to disseminate correct knowledge regarding oral health, as well as provide information to reduce and treat risk factors such as dental caries, periodontal disease, and occlusal problems. In particular, use of mouthguard is one of the most effective ways to prevent sports-related dental injuries that occur in sports and physical activity participants. Recently, along with increased health consciousness, the number of individuals who participate in sports and fitness activities is also increasing. Outside of the bounds of conventional dental clinical treatment, dentists are encouraged to actively be involved in local and regional organizations related to sports, recreation, and physical activity opportunities, in order to contribute to promotion of safety and health, including injury prevention. In this review, we discuss various findings to prevention of sports-related dental injuries in children