Yukari Suzuki, Takamasa Kitamura, Kei Maeo, Tomohiro Kizuki, Mayu Noda, Hitomi Kuramoto, Yuki Akazawa, Hitomi Ishii, Akihiro Haga, Ryuzo Kanomi and Tomonori Iwasaki : Comprehensive Study on Quantitative Evaluation of Oral Muscle Tissue in Children With Low Tongue Posture Using Cone Beam Computed Tomography: A Comprehensive Study on Nasal Ventilation Conditions Using Computational Fluid Dynamics, Journal of Oral Rehabilitation, 53, 7, 1337-1346, 2026.
(要約)
Low tongue posture (LTP) results from nasal obstruction and impaired oral muscle function. However, the relationship between nasal obstruction-independent LTP and oral muscle function remains unclear. In this study, we aimed to comprehensively examine the relationship between nasal obstruction-independent LTP and oral muscle function by evaluating LTP, nasal ventilation conditions, and oral muscle function based on the cross-sectional area of the muscle-fat tissue surrounding the oral cavity. Participants included 28 children (LTP group: mean age: 8.71 years) with LTP and 24 children (control group: mean age: 8.89 years) without LTP. Nasal airway ventilation conditions were evaluated using nasal fluid analysis of the cone beam computed tomography (CBCT) data. Oral muscle function was assessed by measuring the cross-sectional area of muscle-fat in the upper and lower lips, upper and lower oral vermilions, and tongue using CBCT data. Compared with the control group, the LTP group exhibited higher nasal airway pressure and reduced muscle cross-sectional areas in the lower lip, lower orbicularis oris, and tongue. The LTP group without nasal obstruction had significantly smaller muscle cross-sectional areas of the lower lip and tongue than the group without LTP. The group without LTP but with nasal obstruction had a significantly larger tongue muscle cross-sectional area than the LTP group. LTP can involve nasal obstruction and reduced muscle components in the lower lip, orbicularis oris, and especially the tongue, being related to lower muscle function. The findings could help improve the management of LTP-associated disorders.
Katsuhiro Mieda, Tadashi Nakanishi, Hitomi Kuramoto, Yoshitaka Hosokawa, Ikuko Hosokawa, Daisuke Takegawa and Keiichi Hosaka : Sudachitin reduces inflammatory mediator expression in toll-like receptor 2 ligand-stimulated human dental pulp cells, Cell Biochemistry and Biophysics, 83, 2, 2431-2439, 2025.
(要約)
Sudachitin, which is a polymethoxy flavonoid derived from the peer of Citrus sudachi, has several biological properties. However, the effect of sudachitin on human dental pulp cells (HDPCs) remains unclear. The aim of this study was to investigate whether sudachitin could decrease the expression of inflammatory mediators such as cytokines and prostaglandin in HDPCs stimulated with Pam3CSK4, a ligand for toll-like receptor (TLR) 2. HDPCs were pre-incubated with different concentrations of sudachitin (6.25, 12.5, 25, or 50 μM) and stimulated with Pam3CSK4 (100 ng/mL). The quantification of inflammatory cytokines (interleukin (IL)-6, IL-8, and C-X-C motif chemokine ligand (CXCL) 10) and prostaglandin E (PGE) were performed by enzyme-linked immunosorbent assay (ELISA). The expression of cyclooxygenase (COX)-2, a key enzyme for PGE formation, was analyzed by western blot. Moreover, the activations of cell signal pathways were examined by western blot analysis. Sudachitin suppressed IL-6, IL-8, CXCL10, and PGE production and COX-2 protein expression in Pam3CSK4-stimulated HDPCs. In addition, we revealed that nuclear factor-kappa B (NF-κB) and protein kinase B (Akt) pathways in the Pam3CSK4-stimulated HDPCs were inhibited by sudachitin treatment. These findings suggest that sudachitin can reduce inflammatory mediator production in HDPCs stimulated with TLR2 ligand by inhibiting NF-κB and Akt activations.
Ikuko Hosokawa, Hitomi Kuramoto, Yoshitaka Hosokawa and Keiichi Hosaka : Tooth Bleaching to Bring out the Patients Smile -Initiatives in Department of Cariology at Tokushima University Hospital-, Journal of Oral Health and Biosciences, 37, 2, 32-37, 2025.
(要約)
In recent years, in our super-aged society, where people are striving for health and longevity, aesthetic awareness and interest in the oral cavity are increasing among men and women of all ages and both sexes. In particular, the number of patients requesting tooth bleaching procedures for discolored teeth has been increasing. Tooth bleaching is a minimally invasive esthetic dentistry that can make patients smile. To meet the needs of these patients, Department of Cariology at the University of Tokushima Hospital has reestablished a system for patients to receive tooth bleaching treatment for discolored teeth. Therefore, we would like to report on the bleaching procedures we are performing at our department.
Daisuke Takegawa, Yoshihito Naitou, Kohichi Kani, Takaaki Tsunematsu, Hitomi Kuramoto and Tadashi Nakanishi : Severe Root Resorption with Pulp Fibrosis Despite Normal Responses to Pulp Sensibility Tests: A Case Report, Operative Dentistry, Endodontology and Periodontology, 5, 1, 70-76, 2025.
(要約)
<p> Purpose: We report a rare case of atypical external root resorption in the mid-root region of a mandibular molar following direct pulp capping (DPC), despite the tooth consistently exhibiting normal responses to pulp sensibility tests. We discuss the diagnostic challenges presented by such cases, focusing on the limitations of conventional pulp testing, the potential role of pathological pulp fibrosis, and the importance of cone-beam computed tomography (CBCT) in early detection and accurate diagnosis.</p><p> Case: A 38-year-old male patient presented with a chief complaint of chronic discomfort and distal gingival swelling in the right mandibular second molar. The tooth had undergone DPC with calcium hydroxide nine years earlier due to pulp exposure following complete caries removal. Clinical examination revealed mild gingival swelling and slight tenderness to percussion, with normal periodontal probing depths. The electric pulp test (EPT) and cold test showed normal responses, which were consistent with the results from a previous visit six years earlier. A dental radiograph taken six years earlier showed no abnormalities; however, comparison with the radiograph obtained at presentation revealed extensive external root resorption localized to the mid-root area of the mesial root. CBCT images confirmed that the resorption had perforated the dentin and reached the pulp chamber, accompanied by substantial loss of lingual alveolar bone. The prognosis was ultimately deemed poor, and the tooth was extracted. The extracted tissue was subjected to histopathological examination using hematoxylin and eosin staining. Histopathological analysis revealed extensive fibrosis in the pulp tissue without bacterial infection. In addition, chronic inflammatory granulation tissue, mainly with neutrophil infiltration, was observed in the area of external root resorption.</p><p> Discussion: This case highlights the limitations of relying solely on pulp sensibility tests for assessing pulp health. Especially in teeth with a history of DPC and chronic symptoms, underlying pathological changes, such as fibrosis, may not alter nerve responses until later stages. Atypical external root resorption can occur secondary to these changes, potentially progressing significantly without typical symptoms or radiographic signs on conventional 2D imaging. CBCT proved useful for identifying the precise location, extent, and perforation of the resorption lesion, underscoring its value in diagnosing complex endodontic-periodontal conditions.</p><p> Conclusion: Early use of CBCT should be considered in teeth with persistent symptoms after DPC, even in patients with normal pulp sensibility tests results, to facilitate timely diagnosis and appropriate management.</p>
(キーワード)
root resorption / electric pulp test (EPT) / cone-beam computed tomography (CBCT)
Yukari Suzuki, Takamasa Kitamura, Kei Maeo, Tomohiro Kizuki, Mayu Noda, Hitomi Kuramoto, Yuki Akazawa, Hitomi Ishii, Ryuzo Kanomi and Tomonori Iwasaki : MuscleFat Composition Analysis of the Soft Palate in Mouth-breathing Children Using Cone-beam Computed Tomography: A Computational Fluid Dynamics Study, International Journal of Clinical Pediatric Dentistry, 2025.
Tadashi Nakanishi, Katsuhiro Mieda, Hitomi Kuramoto and Daisuke Takegawa : Effect of interleukin-17A on inflammatory mediator production in interleukin-1β-stimulated human dental pulp fibroblasts, European Journal of Oral Sciences, 132, 5, e13019, 2024.
(要約)
In response to pro-inflammatory cytokines such as interleukin (IL)-1β, dental pulp fibroblasts produce various inflammatory mediators, including IL-6, IL-8, CC chemokine ligand 20 (CCL20), and CXC chemokine ligand 10 (CXCL10), leading to the progression of pulpitis. IL-17/IL-17A (IL-17A) is a pro-inflammatory cytokine secreted by T helper (Th) 17 cells following their recruitment to inflamed sites; however, the roles of IL-17A during pulpitis remain unclear. The purpose of this study was to investigate the effect of IL-17A on IL-6, IL-8, CCL20 and CXCL10 production by human dental pulp fibroblasts (HDPFs) in vitro. IL-17A at a concentration of 100 ng/ml induced the production of 10 times more IL-8 and 4 times more CXCL10, but not IL-6 and CCL20, compared to controls. Co-stimulation of HDPFs with IL-17A and IL-1β synergistically enhanced the production of IL-6, CCL20, IL-8 and CXCL10. IL-1β increased expression of IL-17 receptor/IL-17RA (IL-17R) on HDPFs. Moreover, the cell signal pathways of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) were more potently activated by simultaneous stimulation with IL-17A and IL-1β. These findings suggest that IL-17A participates in the progression of dental pulp inflammation through the enhanced production of inflammatory mediators in HDPFs.
Hitomi Kuramoto, Tadashi Nakanishi, Daisuke Takegawa, MIEDA Katsuhiro and Keiichi Hosaka : Caffeic Acid Phenethyl Ester Induces Vascular Endothelial Growth Factor Production and Inhibits CXCL10 Production in Human Dental Pulp Cells, Current Issues in Molecular Biology, 44, 11, 5691-5699, 2022.
(要約)
The survival rate of root non-vital teeth is lower than that of vital teeth. Therefore, to preserve the dental pulp is very important. The vascular endothelial growth factor (VEGF) is the most potent angiogenic factor involved in the vitality of dental pulp including reparative dentin formation. Caffeic acid phenethyl ester (CAPE) is a physiologically active substance of propolis and has some bioactivities such as anti-inflammatory effects. However, there are no reports on the effects of CAPE on dental pulp inflammation. In this study, we investigated the effects of CAPE on VEGF and inflammatory cytokine production in human dental pulp cells (HDPCs) to apply CAPE to an ideal dental pulp protective agent. We found that CAPE induced VEGF production from HDPCs. Moreover, CAPE induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases (ERK), and stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) in HDPCs. Furthermore, CAPE inhibited C-X-C motif chemokine ligand 10 (CXCL10) production in Pam3CSK4- and tumor necrosis factor-alpha (TNF-α)-stimulated HDPCs. In conclusion, these results suggest that CAPE might be useful as a novel biological material for vital pulp therapy by exerting the effects of VEGF production and anti-inflammatory activities.
Hitomi Kuramoto, Kouji Hirao, Hiromichi Yumoto, Yuki Hosokawa, Tadashi Nakanishi, Daisuke Takegawa, Ayako Washio, Chiaki Kitamura and Takashi Matsuo : Caffeic acid phenethyl ester (CAPE) induces VEGF expression and production in rat odontoblastic cells, BioMed Research International, Article ID 5390720, 2019.
(要約)
Caffeic acid phenethyl ester (CAPE), the main component of propolis, has various biological activities including anti-inflammatory effect and wound healing promotion. Odontoblasts located in the outermost layer of dental pulp play crucial roles such as production of growth factors and formation of hard tissue termed reparative dentin in host defense against dental caries. In this study, we investigated the effects of CAPE on the upregulation of vascular endothelial growth factor (VEGF) and calcification activities of odontoblasts, leading to development of novel therapy for dental pulp inflammation caused by dental caries. CAPE significantly induced mRNA expression and production of VEGF in rat clonal odontoblast-like KN-3 cells cultured in normal medium or osteogenic induction medium. CAPE treatment enhanced nuclear factor-kappa B (NF-B) transcription factor activation, and furthermore, the specific inhibitor of NF-B significantly reduced VEGF production. The expression of VEGF receptor- (VEGFR-) 2, not VEGFR-1, was up regulated in KN-3 cells treated with CAPE. In addition, VEGF significantly increased mineralization activity in KN-3 cells. These findings suggest that CAPE might be useful as a novel biological material for the dental pulp conservative therapy.
Hiromichi Yumoto, Kouji Hirao, Yuki Hosokawa, Hitomi Kuramoto, Daisuke Takegawa, Tadashi Nakanishi and Takashi Matsuo : The Roles of Odontoblasts in Dental Pulp Innate Immunity, Japanese Dental Science Review, 54, 3, 105-117, Aug. 2018.
(要約)
Odontoblasts located in the outermost layer of dental pulp form a natural barrier between mineralized tissues, dentin, and soft tissues, dental pulp, of the vital tooth, and they first recognize caries-related pathogens and sense external irritations. Therefore, odontoblasts possess a specialized innate immune system to fight oral pathogens invading into dentin. Generally, the rapid initial sensing of microbial pathogens, especially pathogen-associated molecular patterns (PAMPs) shared by microorganisms, are mediated by pattern recognition receptors (PRRs), such as Toll-like receptor and the nucleotide-binding oligomerization domain (NOD). The innate immune responses in odontoblasts initiated by sensing oral pathogens provide host protective events, such as inflammatory reactions, to produce a variety of pro-inflammatory mediators, including chemokines and cytokines. These attract various inflammatory cells and cause antibacterial reactions, such as the production of defensins, to kill microorganisms in the proximal region of the odontoblast layer. This review focuses on innate immunity, especially cellular and molecular mechanisms regarding the sensing of PAMPs from oral pathogens by PRRs, in odontoblasts and provides information for future studies for the development of novel therapeutic strategies, including diagnosis and treatment, to prevent exceeding dental pulp inflammation and preserve the dental pulp tissues.
Hiromichi Yumoto, Kouji Hirao, Yuki Hosokawa, Hitomi Kuramoto, Katsuhiko Hirota, Yoichiro Miyake and Takashi Matsuo : Streptococcal histone-like DNA binding protein induces MINCLE expression on monocytes, 95th General Session & Exhibition of the International Association for Dental Research, San Francisco, Mar. 2017.
2.
Yuki Hosokawa, Hiromichi Yumoto, Kouji Hirao, Hitomi Kuramoto, Tadashi Nakanishi, Daisuke Takegawa and Takashi Matsuo : Anti-inflammatory effects of polyphenols on rat odontoblastic cells, 95th General Session & Exhibition of the International Association for Dental Research (San Francisco), Mar. 2017.