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Objectives: To elucidate the imaging characteristics of the gubernaculum tract (GT) in patients with cleidocranial dysplasia (CCD) as visualized with computed tomography (CT)., Study Design: This was a retrospective analysis of the presence and shape of GTs of unerupted permanent teeth and supernumerary teeth on CT in 9 patients with CCD., Results: The overall GT detection rate for unerupted permanent teeth was 83.5% (81/97), with no significant difference between permanent teeth without and with adjacent supernumerary teeth (P = .414). The overall GT detection rate for unerupted supernumerary teeth was 83.1% (49/59). Of the 156 total unerupted teeth analyzed, 83.3% (130/156) were judged to have GTs. No significant difference in detection rate of GTs was found between permanent and supernumerary teeth (P > 0.999). A composite morphology consisted of a single GT for a permanent unerupted tooth with 1 or 2 supernumerary teeth in which the dental follicles of the permanent and supernumerary teeth were confluent. In total, 44 groups consisted of 1 permanent and 1 or 2 supernumerary teeth; 79.5% (35/44) had GTs., Conclusions: A specific composite structure of GTs and dental follicles may signify that 2 or 3 teeth are derived from a single dental lamina in patients with CCD. In such cases, tooth eruption may fail due to the presence of only 1 GT for multiple teeth., Competing Interests: DECLARATION OF INTERESTS None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Since there are many differential diagnoses for cemento-osseous dysplasia (COD), it is very difficult for dentists to avoid misdiagnosis. In particular, if COD is related to an embedded tooth, differential diagnosis is difficult. However, there have been no reports on the characteristics of the imaging findings of COD associated with embedded teeth. The aim of the present study was to investigate the occurrence and imaging characteristics of cemento-osseous dysplasia (COD) associated with embedded teeth, in order to appropriately diagnose COD with embedded teeth., Methods: The radiographs with or without histological findings of 225 patients with COD were retrospectively analyzed. A retrospective search through the picture archiving and communication system (PACS) of the Division of Oral and Maxillofacial Radiology of Kyushu Dental University Hospital was performed to identify patients with COD between 2011 and 2022., Results: Fifteen COD-associated embedded mandibular third molars were identified in 13 patients. All 13 patients were asymptomatic. On imaging, COD associated with embedded mandibular third molars appeared as masses that included calcifications around the apex of the tooth. On panoramic tomography, COD showed inconspicuous internal calcification similar to that of odontogenic cysts or simple bone cysts, especially in patients with COD only around the mandibular third molar region. Those with prominent calcification resembled cemento-ossifying fibroma, calcifying epithelial odontogenic tumor, calcifying odontogenic cyst, adenomatoid odontogenic tumor, and so on, as categories of masses that include calcifications on panoramic tomography and computed tomography., Conclusions: The current investigation is the first to report and analyze the imaging characteristics of COD associated with embedded teeth. It is important to consider the differences between COD and other cystic lesions on panoramic tomography, and the differences between COD and masses that include calcifications on CT.

Background: Very recently, a significant relationship between tonsilloliths and dental plaque-related pathologies was reported using digital panoramic radiographs. Their dynamics over time suggest that tonsilloliths may be in a permanently active phase that functions to remove foreign matter. The aim of the study was to evaluate the relationship between the occurrence of tonsilloliths and the extent of periodontitis., Methods: A total of 608 patients who underwent both CT and panoramic radiographs were included in the study. Both of two imaging were retrospectively and independently assessed with respect to the presence of tonsilloliths detected on CT and panoramic radiographs, and bone defects caused by periodontitis detected on panoramic radiographs. The type of retrospective study is case-control. Then, the differences between age groups were evaluated with respect to the degree of bone resorption and its correlation with the presence of tonsilloliths. The relationships between categorical variables were assessed using Pearson's correlation coefficient or Spearman's correlation coefficient., Results: There was a significant relationship between tonsilloliths on CT and the extent of the bone defect on panoramic radiographs (Spearman's correlation coefficient, r = 0.648, p = 0.043). In addition, there was a significant difference in the extent of the bone defect caused by periodontitis between subjects with and without tonsilloliths in the 60 to 69-year-old group (Mann-Whitney U test, p = 0.025), 70 to 79-year-old group (Mann-Whitney U test, p = 0.002), and 80 to 89-year-old group (Mann-Whitney U test, p = 0.022), but not in other age groups (Mann-Whitney U test: under 9-year-old group, p = 1.000; 10 to 19-year-old group, p = 1.000; 20 to 29-year-old group, p = 0.854; 30 to 39-year-old group, p = 0.191, 40 to 49-year-old group, p = 0.749; 50 to 59-year-old group, p = 0.627; ≥90-year-old group, p = 1.000)., Conclusions: The presence of tonsilloliths was related to the extent of periodontitis because the structures were responding dynamically., (© 2023. The Author(s).)

Background: The distribution and drainage of the sublingual gland ducts have various patterns that might be related to sublingual gland-related diseases, including ranula. This study aimed to elucidate the characteristics of the distribution of Bartholin and/or Rivinus ducts in patients with ranula using magnetic resonance (MR) sialography., Methods: In this retrospective cross-sectional study, the distributions and drainage patterns of sublingual gland ducts on MR sialography were classified in 74 subjects without sublingual gland-related disease as confirmed by both medical history and clinical examination and 15 patients with ranula, respectively. All patients had visited Kyushu Dental University Hospital from July 2015 to June 2022 to undergo MR imaging. Data on the distributions and drainage patterns of the sublingual gland ducts, including the characteristics of the Bartholin and/or Rivinus ducts, were then statistically compared between subjects without sublingual gland-related disease and patients with ranula. The images were assessed by an experienced oral and maxillofacial radiology specialist certified by the Japanese Society for Oral and Maxillofacial Radiology. The distributions (five groups) and drainage patterns (three patterns) of the sublingual gland ducts on MR sialography were classified in reference to previous studies, with some modifications in all subjects without sublingual gland-related disease and patients with ranula., Results: A significant difference in the distribution of the ducts (P<0.001), with a low number of patients exposing an undetected canal or Rivinius duct, was found in the group of patients with ranula (P<0.05). Regarding drainage patterns, no patient with ranula presented a Rivinius duct only. A significant difference in the drainage patterns of the sublingual gland ducts on MR sialography was observed between subjects without sublingual gland-related disease and patients with ranula (P=0.001)., Conclusions: The present results suggest that the distribution of the sublingual gland ducts, mainly, the Bartholin duct, may be related to ranula formation. These findings also demonstrate that MR sialography contributes well to preoperative evaluation and is effective for assessing the complex excretory distribution of the sublingual gland ducts., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-948/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

The aim of this prospective cohort study was to compare changes in nasal cavity and function between Le Fort I with and without horseshoe osteotomy after superior repositioning of the maxilla. The patients were divided into 2 groups, a Le Fort I alone (LF alone) group and a combination Le Fort I and horseshoe osteotomy (HS) group. The nasal cavity volume was measured using 3-dimensional computed tomographic images, and nasal resistance was assessed by anterior active mask rhinomanometry. The HS group consisted of 17 patients, and the LF alone group consisted of 15 patients. The magnitude of change in nasal cavity volume was significantly smaller in the HS group than in the LF alone group (p < 0.001), even though the mean amount of superior maxillary movement was considerably larger in the HS group than in the LF alone group (p < 0.001). Mean nasal resistance was significantly smaller postoperatively than preoperatively in the HS group (p < 0.05). Furthermore, the change in nasal resistance was smaller in the HS group than in the LF alone group (p < 0.001). Within the limitations of this study, it seems that horseshoe osteotomy is useful for maintaining the nasal cavity and function after superior repositioning of the maxilla., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2023 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Cancer stem cells (CSCs) are considered to be responsible for recurrence, metastasis, and resistance to treatment in many types of cancers; therefore, new treatment strategies targeting CSCs are attracting attention. In this study, we fabricated a polyethylene glycol-tagged microwell device that enabled spheroid formation from human oral squamous carcinoma cells. HSC-3 and Ca9-22 cells cultured in the microwell device aggregated and generated a single spheroid per well within 24-48 h. The circular shape and smooth surface of spheroids were maintained for up to five days, and most cells comprising the spheroids were Calcein AM-positive viable cells. Interestingly, the mRNA expression of CSC markers ( Cd44 , Oct4 , Nanog , and Sox2 ) were significantly higher in the spheroids than in the monolayer cultures. CSC marker-positive cells were observed throughout the spheroids. Moreover, resistance to cisplatin was enhanced in spheroid-cultured cells compared to that in the monolayer-cultured cells. Furthermore, some CSC marker genes were upregulated in HSC-3 and Ca9-22 cells that were outgrown from spheroids. In xenograft model, the tumor growth in the spheroid implantation group was comparable to that in the monolayer culture group. These results suggest that our spheroid culture system may be a high-throughput tool for producing uniform CSCs in large numbers from oral cancer cells.

The purpose of this study was to elucidate the imaging characteristics of the gubernaculum tracts in successional teeth related to fused deciduous teeth on computed tomography. The imaging findings of 15 gubernaculum tracts in successional teeth related to fused deciduous teeth were retrospectively analyzed using cone-beam computed tomography or multidetector computed tomography. In cases without a congenitally defected successor, the two gubernaculum tracts of two successional teeth related to fused deciduous teeth were fused into one. Gubernaculum tracts (GTs) in mesial successors were vertical, but in distal successors they were inclined to mesial. The major abnormalities of the successional teeth related to fused deciduous teeth were delayed eruption and delayed formation. No inclined mesial successors were found, whereas most of the distal successors were inclined to mesial along with the inclined GT. The gubernaculum tracts of successors with a congenital defect of the other successors were vertical, and such successors had no abnormalities. The present study showed the imaging characteristics of gubernaculum tracts in successional teeth related to fused deciduous teeth. The abnormal eruption of successional teeth related to fused deciduous teeth may be associated with the characteristics of their gubernaculum tracts., (© 2022 The Authors. Congenital Anomalies published by John Wiley & Sons Australia, Ltd on behalf of Japanese Teratology Society.)

This study investigated the relationship between the direction of maxillary repositioning after Le Fort I osteotomy and changes in external nasal morphology using lateral cephalograms and frontal facial photographs. The results indicated greater changes in external nasal morphology, such as a more forward position of the nasal tip and an increased alar base width, with anterosuperior repositioning than with posterosuperior repositioning. In conclusion, this study demonstrated that the external nasal morphology changes after Le Fort I osteotomy, and that the changes vary depending on the direction of maxilla repositioning.

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse side effect of antiresorptive agents. However, withdrawal of such agents in patients with osteoporosis may increase the risk of fracture. The treatment of MRONJ is challenging, and standard treatment guidelines have yet to be established. In this study, the aim was to find out whether adjuvant daily or weekly teriparatide (TPTD) injections were beneficial for exposed bony MRONJ lesions compared with standard conservative management. We also studied the complications and the patients' response to TPTD therapy. We enrolled 27 patients (January 2012 - December 2016) with chronic and refractory MRONJ. There were four men and 23 women (85% female). Nine patients who did not select TPTD therapy for several reasons formed the non-TPTD group; the remaining 18 were randomly assigned to the daily (n=9) or weekly (n=9) groups. All patients in both groups continued standard conservative therapy in addition to their daily or weekly subcutaneous injection of TPTD (20 μg or 56.5 μg, respectively). We evaluated the complications of TPTD and its benefits. Three patients in the daily group did not complete the study, resulting in six patients in the daily group, nine in the weekly group, and nine in the non-TPTD group in the final analysis. The exposed bone was completely covered with normal mucosa in all patients in the TPTD groups, and the healing period was shorter than that in the non-TPTD group. No patient had complications of atypical fractures of the femoral head. Daily and weekly TPTD treatment resulted in a shortened treatment period compared with standard conservative therapy, with no increase in the rate of complications or worsening of osteoporosis., Competing Interests: Conflict of interest We have no conflicts of interest., (Copyright © 2021 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objectives: The shapes of gubernaculum tracts (GTs) in molars as accessional teeth remain unidentified. To elucidate imaging peculiarities of GTs in molars with aging on multidetector-row computed tomography (MDCT)., Material and Methods: This retrospective study was conducted using CT images, including maxillary and mandibular molars, with no abnormal findings from 239 patients. Shapes of alveolar bone, GTs, and dental sacs of the maxillary and mandibular molars were analyzed multi-sectionally. Correlations between 2- and 3-dimensional imaging figures of GTs in molars and chronological age or stage of molar formation were analyzed., Results: Some forms of GTs in maxillary and mandibular third molars were observed. In the early stage, GTs were visualized as bone defect lines on the dentition and grooves on the mesial alveolar crest continuous with the dental sac to mesial tooth bud. GTs of the third molar formed a J-shape in maxillary teeth and Y-shape in mandibular teeth in the middle stage, as alveolar bone around the GT developed. In the mature stage, the course of the GT changed to straight and perpendicular. Some GT forms were also identified in first and second molars. Significant correlations were found between GT alterations and chronological age or stage of molar formation. Moreover, tracts continuing from the distal side of mandibular third molars were detected., Conclusions: This paper describes the peculiarities and process of progression for GTs in molars, and the existence of tracts continuing from the distal side of mandibular third molars, unlikely dentition with deciduous predecessors. These preliminary data should prove beneficial for studies focusing on GTs in molars., (© 2021 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

The eruption pathway from the dental follicle to the gingiva for permanent teeth is known as the gubernaculum tract (GT), a physiologic structure thought to play a role in tooth eruption. Cone beam computed tomography and multi-detector computed tomography have recently been used to visualize the GT, with the results indicating that this structure might be related to the normal eruption of teeth. By contrast, curved and/or constricted GTs may lead to abnormal tooth eruption. In addition, complex odontomas have been reported from within the GT or dental sac of unerupted permanent teeth. If an odontoma occurs within the GT, the tooth will not erupt normally. Moreover, the imaging characteristics of the GT from the top of the odontogenic mass to the alveolar crest are extremely useful for making a differential pathological diagnosis and for differentiating between odontogenic and non-odontogenic masses. Therefore, radiological studies on the GT have been attracting increasing attention. Given this background, the present review aims to clarify the imaging characteristics and review recent studies on the GT considering the importance of the research.

Objective: Cleft palate is among the most frequent congenital defects in humans. While gene-environment multifactorial threshold models have been proposed to explain this cleft palate formation, only a few experimental models have verified this theory. This study aimed to clarify whether gene-environment interaction can cause cleft palate through a combination of specific genetic and environmental factors., Methods: Msx1 heterozygosity in mice ( Msx1 +/- ) was selected as a genetic factor since human MSX1 gene mutations may cause nonsyndromic cleft palate. As an environmental factor, hypoxic stress was induced in pregnant mice by administration of the antiepileptic drug phenytoin, a known arrhythmia inducer, during palatal development from embryonic day (E) 11 to E14. Embryos were dissected at E13 for histological analysis or at E17 for recording of the palatal state., Results: Phenytoin administration downregulated cell proliferation in palatal processes in both wild-type and Msx1 +/- embryos. Bone morphogenetic protein 4 ( Bmp4 ) expression was slightly downregulated in the anterior palatal process of Msx1 +/- embryos. Although Msx1 +/- embryos do not show cleft palate under normal conditions, phenytoin administration induced a significantly higher incidence of cleft palate in Msx1 +/- embryos compared to wild-type littermates., Conclusion: Our data suggest that cleft palate may occur because of the additive effects of Bmp4 downregulation as a result of Msx1 heterozygosity and decreased cell proliferation upon hypoxic stress. Human carriers of MSX1 mutations may have to take more precautions during pregnancy to avoid exposure to environmental risks.

Background: Tonsilloliths are related clinically to halitosis and tonsillar abscess. However, the dynamics of tonsilloliths over time are unknown. The aim of the study was to evaluate change in the characteristics of tonsilloliths in a time-dependent fashion by follow-up computed tomography (CT)., Methods: Tonsilloliths were analyzed in 326 CT scan pair sets of initial and at least two follow-up CT examinations of patients with whole palatine tonsils and various diseases of the oral and maxillofacial regions., Results: Over the follow-up period, 12.1% of tonsilloliths disappeared. Approximately 26.1% of tonsilloliths changed in size during follow-up, mostly increasing in size. In tonsilloliths that showed enlargement, the mean (± standard deviation) growth rate was 0.61 ± 0.41 mm per year. Approximately 37.3% of tonsilloliths changed position during the follow-up period; of these, movement was toward the respiratory tract in 92% at a mean rate of - 1.38 ± 1.59 mm per year. The calcification levels of almost all tonsilloliths showed dynamic change: HU number increased in 84.3% and decreased in 12.7% of tonsilloliths over the follow-up period. The mean rate of HU increase was 63.8 ± 96.3 HU/year, and the mean rate of HU decrease was - 38.4 ± 66.8 HU/year., Conclusions: The calcification levels of all tonsilloliths showed dynamic fluctuation, and a tendency for excretion of tonsilloliths from the body. Their dynamics over time suggest that tonsilloliths may be in a permanently active phase which functions to remove foreign matter.

Objectives: We evaluated the relationships between depth of invasion (DOI) of tongue cancer, as measured with preoperative T1- and T2-weighted magnetic resonance imaging (MRI) and postoperative histopathologic (Path) specimens, with cervical lymph node metastasis (CLNM) and tumor stage. We also calculated the correlation of MRI and Path DOI measurements., Study Design: This retrospective study included 101 patients who had squamous cell carcinoma of the tongue and were treated surgically. Two observers measured DOI on all 3 modalities., Results: DOI thresholds for predicting CLNM with high diagnostic efficacy were 6.99 mm and 8.32 mm for MRI and 5 mm for Path. DOI values from all modalities were significantly different for tumors with and without CLNM (P < .01) and for the 4 TNM stages (P ≤ .05), with increasing values corresponding to advancement in tumor stage. Addition of DOI changed the T level of many tumors based on the new TNM (tumor-node-metastasis) classification. The correlation coefficient between DOI calculated on each MRI sequence and Path was 0.90., Conclusions: MRI-derived DOI accurately reflected the subsequent metastatic status and degree of progression of tumor stages, with a strong positive correlation to Path values, and may be considered a predictor of tumor stage and CLNM., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A simple sandwich technique using buttons to compress grafted tissue combined with a tie-over technique for intraoral split-thickness skin grafts (STSGs) is introduced. This technique yielded an excellent engraftment rate (90.5%) and no instances of total graft failure were recorded. This simple sandwich technique for STSGs is readily applicable and inexpensive, and the present results show that it would be potentially useful for repair of defects in the oral cavity.

This study was done to determine whether the sublingual gland ducts could be visualized and/or their function assessed by MR sialography and dynamic MR sialography and to elucidate the clinical significance of the visualization and/or evaluation of the function of sublingual gland ducts by clinical application of these techniques. In 20 adult volunteers, 19 elderly volunteers, and 7 patients with sublingual gland disease, morphological and functional evaluations were done by MR sialography and dynamic MR sialography. Next, four parameters, including the time-dependent changes (change ratio) in the maximum area of the detectable sublingual gland ducts in dynamic MR sialographic images and data were analyzed. Sublingual gland ducts could be accurately visualized in 16 adult volunteers, 12 elderly volunteers, and 5 patients. No significant differences in the four parameters in detectable duct areas of sublingual glands were found among the three groups. In one patient with a ranula, the lesion could be correctly diagnosed as a ranula by MR sialography because the mass was clearly derived from sublingual gland ducts. This is the first report of successful visualization of sublingual gland ducts. In addition, the present study suggests that MR sialography can be more useful in the diagnosis of patients with lesions of sublingual gland ducts.

Background: Therapeutic strategies for patients with medication-related osteonecrosis of the jaw (MRONJ) remain controversial. The aim of the present study was to clarify the effectiveness and safety of teriparatide therapy in Japanese MRONJ patients based on a large number of case series with a multicenter retrospective analysis., Patients and Methods: Between January 2012 and December 2016, 29 patients who were diagnosed with MRONJ at 10 hospitals were treated with teriparatide. The medical records of these patients were retrospectively reviewed to assess the efficacy and safety of teriparatide therapy for MRONJ patients., Results: Adverse events occurred in 17.2% of patients (5/29). One patient developed severe arthralgia and discontinued teriparatide therapy after 12 days, while others continued the treatment. Among 29 patients, the median period of administration of teriparatide was 14.0 months (range, 0.3-26 months), and treatment outcomes were evaluated as effective in 75.9% of patients with complete resolution in 65.5%. Among patients treated with oral bisphosphonates (BPs), 83.3% were effectively treated with teriparatide and 40% with intravenous BPs. The oral administration of BPs was associated with successful treatment outcomes with teriparatide (p = 0.062)., Conclusions: Teriparatide therapy has potential as an effective treatment option for MRONJ., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to evaluate whether a new cine-magnetic resonance imaging (CMRI) technique might be useful for evaluating swallowing function in patients with different types of oral cancers by assessing 12 CMRI-related parameters., Study Design: In total, 111 patients with oral cancers were evaluated. We examined whether visualization of fluid flow and determination of flow direction to the trachea or the esophagus were possible with CMRI. We evaluated the correlations between CMRI-related parameters and self-reported dysphagia scores as the status of dysphagia, T classification groups as tumor staging for preoperative patients, alterations in CMRI-related parameters between pre- and postoperative patients, and the degree of invasiveness of oral cancer surgery., Results: We could judge the flow direction to the esophagus on CMRI in all 111 patients. Six CMRI-related parameters showed significant correlations with dysphagia status. Increases in CMRI-related parameters were significantly related to deterioration of swallowing status, as shown by a decrease in self-reported dysphagia scores, advances in the T classification, and degree of invasiveness of oral cancer surgery., Conclusions: The results of the present study suggest that CMRI can be used to directly visualize swallowing dynamics and objectively evaluate the swallowing complaints of patients with oral cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Interleukin-17A (IL-17A), a major effector cytokine secreted by T helper 17 (Th17) cells, is elevated in atherosclerosis lesions. The purpose of this study was to assess the role of IL-17A in the pathogenesis of atherosclerosis. To measure the expression of adhesion molecules, human umbilical vein endothelial cells (HUVECs) and U937 cells were stimulated with IL-17A. Western blot and real-time polymerase chain reaction analyses revealed that intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression in HUVECs, and very late antigen-4 (VLA-4), lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (MAC-1) expression in U937 cells was upregulated by IL-17A. Furthermore, IL-17A stimulation resulted in mRNA and protein expression of scavenger receptor (LOX-1) in phorbol 12-myristate 13-acetate (PMA)-activated U937 cells. Oil Red O also demonstrated that IL-17A enhanced foam cell formation by PMA-activated U937 cells induced by oxidized low-density lipoprotein (ox-LDL), and this enhancement of ox-LDL-induced foam cell formation in IL-17A-treated U937 cells was downregulated by transfection of LOX-1 siRNA. These results indicated that IL-17A induced the expression of adhesion molecules, promoted the adherence of monocytes to vascular endothelial cells. IL-17A also stimulated ox-LDL-induced foam cell formation via upregulation of LOX-1 in activated macrophages. IL-17A may be responsible for the pathogenesis of atherosclerosis by inducing the adhesion of leukocytes to vascular endothelium and foam cell formation.

Hyaluronic acid (HA) has a pivotal role in bone and cartilage metabolism. In this study, we investigated the effect and underlying mechanisms of HA accumulation on the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) induced by 1α,25(OH) 2 D 3 and dexamethasone in stromal cells, which support osteoclastogenesis. Degradation of HA by hyaluronidase (HA'ase) treatment enhanced the expression of RANKL in ST2 cells stimulated with 1α,25(OH) 2 D 3 and dexamethasone. Down-regulation of hyaluronan synthase 2 (HAS2) expression by siRNA also stimulated RANKL expression induced by 1α,25(OH) 2 D 3 and dexamethasone. Results from a cell co-culture system with bone marrow cell showed that 1α,25(OH) 2 D 3 and dexamethasone-induced RANKL expression in HA'ase treated- and HAS2 siRNA transfected-ST2 cells was down-regulated by treatment of cells with high molecular weight HA. In contrast, transforming growth factor-β1 (TGF-β1), which stimulates HAS2 expression and HA synthesis, down-regulated RANKL expression induced by 1α,25(OH) 2 D 3 and dexamethasone. Interestingly, knockdown of has2 gene enhanced the expression of vitamin D receptor (VDR) and phosphorylation of signal transducers and activator of transcription 3 (STAT3) in ST2 cells stimulated by 1α,25(OH) 2 D 3 and dexamethasone. These results indicate that accumulation of HA in bone marrow cells may affect RANKL-mediated osteoclast-supporting activity via regulation of VDR and STAT3 signaling pathways., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to evaluate the characteristics of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values of ranulas. In addition, to elucidate DWI findings and ADC values of other representative masses in and around the floor of the mouth., Study Design: DWI findings and ADC values in 35 patients with ranulas and 33 patients with other masses were retrospectively reviewed with a central focus on cystic masses or lesions that may have cyst-like components in and around the floor of the mouth based on the diagnosis of each respective disease., Results: Ranulas were all well-defined, homogeneous masses with high signal intensity on DWI. The mean ± standard deviation ADC value of the 35 ranulas was 2.59 ± 0.31 × 10 -3 mm 2 /s. There was a significant difference in ADC values between simple and plunging ranulas. On DWI, most other masses were heterogeneous, and most ADC values, except those for thyroglossal duct cysts, hemangiomas, and pleomorphic adenomas, were significantly lower than those for ranulas., Conclusions: The characteristic DWI and ADC findings of ranulas can be determined accurately, and these data can be significantly useful in the differential diagnosis of many kinds of diseases in and around the oral floor., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A Stafne bone defect is a static bone depression in the mandible that is commonly observed in cortical bone near the mandibular angle. We herein present a rare case in which static bone depressions attached to the three major salivary glands were observed on panoramic radiography and computed tomography (CT). The three static bone depressions in the mandible were visualized on a panoramic radiograph and CT as oval radiolucent masses in a 68-year-old man. The CT numbers in the bone depressions ranged from 10 to 50 HU, and they were close to those of the respective salivary glands. Based on the CT numbers, the areas in the bone depressions were determined to be a normal parotid gland, sublingual gland, and submandibular gland. The patient underwent a follow-up examination and did not request further consultation.

Fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) play essential roles in bone formation and osteoblast activity through the extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad pathways. Sprouty family members are intracellular inhibitors of the FGF signaling pathway, and four orthologs of Sprouty have been identified in mammals. In vivo analyses have revealed that Sprouty2 is associated with bone formation. However, the mechanism by which the Sprouty family controls bone formation has not been clarified. In this study, we investigated the involvement of Sprouty2 in osteoblast proliferation and differentiation. We examined Sprouty2 expression in MC3T3-E1 cells, and found that high levels of Sprouty2 expression were induced by basic FGF stimulation. Overexpression of Sprouty2 in MC3T3-E1 cells resulted in suppressed proliferation compared with control cells. Sprouty2 negatively regulated the phosphorylation of ERK1/2 after basic FGF stimulation, and of Smad1/5/8 after BMP stimulation. Furthermore, Sprouty2 suppressed the expression of osterix, alkaline phosphatase, and osteocalcin mRNA, which are markers of osteoblast differentiation. Additionally, Sprouty2 inhibited osteoblast matrix mineralization. These results suggest that Sprouty2 is involved in the control of osteoblast proliferation and differentiation by downregulating the FGF-ERK1/2 and BMP-Smad pathways, and suppresses the induction of markers of osteoblast differentiation., (© 2017 The Authors. Cell Biology International Published by by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology.)

We aimed to determine the significance and usefulness of imaging characteristics of gubernaculum tracts (GT) for the diagnosis of odontogenic tumors or cysts. This was a retrospective analysis of relationships between odontogenic or non-odontogenic tumors or cysts and the GT that were visualized using multi-detector computed tomography (MDCT). The relationship between the size of a mass and expansion of the GT in all odontogenic tumors or cysts to which GTs were contiguous on MDCT, was statistically analyzed. Intact or expanded GTs were detected in MDCT images on the top of almost all odontogenic tumors or cysts, but not on non-odontogenic tumors or cysts. Characteristic image findings regarding the relationship between the GT and the odontogenic mass were detected for the respective odontogenic tumors or cysts in which the GTs were contiguous to the mass on MDCT. In ameloblastomas, expansion of the GTs significantly and very strongly correlated with tumor size (r = 0.741, p = 0.0001), but this correlation was very weak in dentigerous cysts (r = 0.167, p = 0.028) and there was no correlation between these parameters in odontogenic keratocysts (r = -0.089, p = 0.557). The imaging characteristics of GTs at the top of masses should be very useful for both the differential diagnosis of the pathological diagnosis of odontogenic masses and for differentiation between odontogenic and non-odontogenic masses., Competing Interests: The authors have declared that no competing interests exist.

Background: Zoledronic acid (Zol), one of the bisphosphonates, is frequently utilized for the treatment of osteoporosis and bone metastasis. However, the onset of medication-related osteonecrosis of the jaw (MRONJ) following dental treatments has become a serious issue. We reported previously that osteonecrosis can be induced by Zol and lipopolysaccharide (LPS) in vivo, suggesting the involvement of Zol in inflammation. Macrophages are divided into M1/M2 macrophages. M1 macrophages are involved in the induction and exacerbation of inflammation and express proinflammatory mediators including interleukin (IL)-1. On the other hand, M2 macrophages are associated with anti-inflammatory reactions through the expression of anti-inflammatory cytokines, such as IL-10. In the present study, we clarified the effects of Zol on M1/M2 macrophage polarization in vitro., Methods: Human monocytic THP-1 cells were polarized to macrophage-like cells by phorbol 12-myristate 13-acetate (PMA), and, after culturing for an additional 24 h with or without Zol, then polarized to M1 macrophages by LPS or to M2 macrophages by IL-4. Cell viability was examined by the WST-8 assay. Gene expression was confirmed by the real-time polymerase chain reaction. Protein expression was detected by western blotting and enzyme-linked immunosorbent assays., Results: Zol treatment upregulated the expression of IL-1β mRNA and protein through NLRP3 inflammasome activation in LPS-treated THP-1 cells. Zol treatment did not affect the expression of IL-10, IL-1ra, or CD206 in IL-4-treated THP-1 cells., Conclusions: Zol enhanced LPS-induced M1, but not M2, macrophage polarization through the NLRP3 inflammasome-dependent pathway, resulting in the production of inflammatory cytokines in THP-1 cells., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objectives: The aim of this study was to determine the usefulness of evaluating the function of swallowing before and after surgery in patients with tongue cancer by using T2-weighted sequences of high-speed continuous magnetic resonance imaging (HSCMRI)., Study Design: The imaging findings and related parameters on HSCMRI along with those on routine MRI examinations before and after surgery were examined in 19 patients with tongue cancer. In addition, changes in various parameters during 1 year after surgery were evaluated in 10 patients., Results: In most patients examined, the direction of flow to the esophagus could be seen on HSCMRI before and after surgery. Significant correlations were observed among 4 parameters and in the responses to a dysphagia questionnaire., Conclusions: The results of the present study suggest that the dynamics of swallowing can be directly visualized on HSCMRI by using 4 parameters that permit the evaluation of changes before and after surgery, and this enables objective evaluation of patients' swallowing complaints., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To elucidate the changes in the distributions of fluorine-18-labelled fluoro-2-deoxy-d-glucose ( 18 F-FDG) accumulation in the tongue muscles of patients following four kinds of surgical operations for tongue cancers., Methods: The changes in the distributions of 18 F-FDG accumulations in the tongue muscles on positron emission tomography (PET)-CT, in association with imaging findings on CT and MRI, were retrospectively analyzed before and after four kinds of surgical operations for 50 patients with tongue cancers., Results: 18 F-FDG-PET-positive areas appeared at the back of the intrinsic muscles of the tongue after invasive surgery for tongue cancers despite the absence of abnormal findings on CT and MRI. A correlation between the standardized uptake value maximum of 18 F-FDG in the intrinsic muscles and the degree of invasiveness of the surgical procedures for tongue cancers (r = 0.539, p < 0.01) was found., Conclusions: It is important to pay attention to the changes in 18 F-FDG distributions in the intrinsic muscles of the tongue before and after invasive surgery despite the absence of abnormal findings on CT and MRI when evaluating the tongue on 18 F-FDG-PET.

Objectives: To elucidate the characteristics of the gubernaculum tracts (GTs) in maxillary anterior teeth with normal or delayed eruption and in mesiodens by using multidetector computed tomography and cone beam computed tomography., Study Design: The characteristics of GTs in maxillary anterior teeth of 205 patients with impacted mesiodens were retrospectively analyzed by using multidetector computed tomography and cone beam computed tomography. The GTs of teeth with normal or delayed eruption and the GTs of mesiodens were examined., Results: The detection ratio of GTs in impacted mesiodens and anterior teeth with delayed eruption was significantly lower than in teeth with normal eruption. A significant difference in the angulation was found between normal and delayed eruptions. Almost all detectable GTs in the inverted mesiodens were derived from the incisive canal, while the remaining were from the alveolar crest. The connecting area of major GTs to tooth in inverted mesiodens was the cervical or root area, but in all other anterior teeth, it was the crown area., Conclusions: GTs of inverted mesiodens may exhibit characteristics that are different from those of normal GTs when the teeth and/or the palate are developing., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The tumor cells were needed to rearrange the extracellular matrix (ECM) and reorganize their cytoskeleton to facilitate the cell motility during the tumor invasion. The proinflammatory cytokine interleukin-17A (IL-17A) is reported to up-regulate tumor invasiveness via ECM degradation by matrix metalloproteinases (MMPs). However the precise effects of IL-17A-dependent invasion remain to be characterized. The aim of this study was to elucidate the mechanisms underlying IL-17A-induced MMP-3 expression in the human synovial sarcoma cells HS-SY-II., Methods: HS-SY-II cells were incubated with IL-17A. In some experiments, the cells were pre-incubated with an anti-IL-17 receptor polyclonal antibody (IL-17R Ab) or inhibitors for signaling cascade prior to addition of IL-17A. The expression of MMP-3 was determined by real-time reverse-transcription polymerase chain reaction (RT-PCR) and western blotting. IL-17R expression in HS-SY-II cells was assessed by immunofluorescence microscopy, while the phosphorylation of signaling molecules was measured by western blotting., Results: IL-17A increased MMP-3 mRNA and protein expression. HS-SY-II cells express the IL-17R on their surface and blockage of IL-17A-IL-17R binding by IL-17R Ab suppressed IL-17A-mediated induction of MMP-3. IL-17A induced the phosphorylation of three components of the mitogen-activated protein kinase (MAPK) pathway including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, and c-Jun NH2-terminal kinase (JNK). Pre-treatment of the cells with inhibitors of ERK1/2, p38 MAPK, and JNK attenuated the IL-17A-induced phosphorylation of activator protein-1 (AP-1) subunits and the expression of MMP-3 mRNA., Conclusion: Our results indicate an essential role for MAPKs in the induction of MMP-3 in synovial sarcoma cells, through AP-1 activation.

Background: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. Although the histopathological findings are diverse, no case of salivary MEC accompanied with bone formation has been reported. Herein, we present the first case of MEC with intratumoral bone formation., Methods and Results: A case of a 75-year-old female patient with an asymptomatic mass of the oral floor is presented. Enhanced CT revealed a tumorous mass with radiopaque materials in the oral floor. A pathological diagnosis of MEC was obtained by biopsy. Radical surgery was performed with the patient under general anesthesia. The resected specimen was finally diagnosed as MEC. Histopathologically, hyalinization, and dystrophic calcification were conspicuous within the stromal components of the tumor. Interestingly, ectopic bone formation was also found in the tumor tissues. Bony materials with osteocyte-like cells were also observed in a series of dystrophic calcification., Conclusion: These findings suggest that bony materials are associated with dystrophic calcification., (© 2015 Wiley Periodicals, Inc.)

There are numerous treatment modalities for mandibular defects after tumor surgery. Autogenous particulate cancellous bone marrow graft combined with titanium mesh (PCBM-MESH) is an alternative procedure. The purpose of this study was to evaluate PCBM-MESH for mandibular reconstruction. There were a total of 10 cases from 2000 to 2011. Mandibles were successfully reconstructed in 9 cases; however, reconstruction failed in 1 case. Overall, the recovery of facial contours was excellent; conversely, the evaluation of prosthetic treatment varied widely. Thus, we suggest 3 steps for mandibular reconstruction: (1) recover the continuity of bone segments; (2) simulate optimum facial contours and dental occlusion; and (3) perform the occlusion with dental prostheses. PCBM-MESH is a valuable method for mandibular defects-particularly for restoring facial contours and a favorable alveolar ridge.

Objective: To elucidate the characteristics of visualizing thin main peripheral vessels in oral and maxillofacial regions of 3-dimensional magnetic resonance angiography (MRA) using a balanced steady-state free-precession (SSFP) sequence with a time-spatial labeling inversion pulse (time-SLIP) and using fresh blood imaging (FBI)., Study Design: The conspicuity of blood vessels and the characteristics on MRA using SSFP with a time-SLIP was compared with those on MRA using FBI in 20 healthy participants., Results: The conspicuity of the main peripheral arteries was significantly higher on MRA using SSFP with a time-SLIP than on MRA using FBI. MRA scans using SSFP were obtained in all participants, and scans using FBI were obtained in 16 of 20 participants. An electrocardiogram was unnecessary when using SSFP but was necessary when using FBI., Conclusions: MRA obtained using SSFP with a time-SLIP is a useful technique to visualize thin main peripheral arteries in the oral and maxillofacial regions without contrast medium., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Recent imaging studies have indicated that the pathophysiology of schizophrenia is closely related to white matter abnormalities and microglial activation. Additionally, recent clinical trials have suggested that atypical antipsychotics may have brain protective properties and that minocycline, an antibiotic with inhibitory effects on microglial activation, improves symptoms of schizophrenia. We have reported that not only atypical antipsychotics with dopamine D2 receptor (D2R) antagonism but also aripiprazole, a unique antipsychotic drug with D2R partial agonism, inhibit microglial activation in vitro. Thus, atypical antipsychotics may exert a beneficial influence on both microglia and oligodendrocytes, while the underlying mechanisms have not been clarified. Here, we investigated whether antipsychotics suppress oligodendrocyte damage by inhibiting microglial activation utilizing a co-culture model with microglia and oligodendrocytes. Pretreatment of aripiprazole and minocycline suppressed apoptosis of oligodendrocytes in the co-culture model with interferon-γ (IFN-γ)-activated microglia, while haloperidol, a traditional antipsychotic drug, did not. Aripiprazole and minocycline inhibited the production of tumor necrosis factor-alpha (TNF-α) from IFN-γ-activated microglia. Moreover, aripiprazole and minocycline attenuated the phosphorylation of signal transducer and activator of transcription 1 (STAT1) in microglia. Overall, our results suggest that aripiprazole and minocycline may have antipsychotic effects through reducing oligodendrocyte damage caused by microglial activation. These results put forward a novel therapeutic hypothesis in schizophrenia research. Future in vivo studies to confirm the present results should be performed., (© 2013.)

Background: Recent studies suggest that tonsilloliths are clinically related to halitosis and tonsillar abscess. Based on our empirical knowledge, tonsilloliths are relatively commonly encountered in daily clinical practice. It has been reported that the detection rate of tonsilloliths was under 24% in previous reports, although experience suggests otherwise. The purpose of the study was to evaluate the prevalence and characteristics of tonsilloliths using computed tomography (CT). In addition, the possible causes of low detection rates on panoramic radiographs were evaluated based on comparisons between CT images and panoramic radiographs in order to elucidate the limitations of visualizing the area around the palatine tonsils on panoramic radiographs., Methods: 482 pairs of CT images and panoramic radiographs were retrospectively assessed with respect to the presence and characteristics of tonsilloliths. In addition, the causes in cases of disagreement between the two modalities were analyzed., Results: The detection rate of tonsilloliths was 46.1% using CT scans, unlike previous reports. The characteristics of tonsillolith were dot-like figures with about 300-500 Hounsfield units within the palatine tonsil under the soft palate. The most common length of tonsilloliths was about 3 or 4 mm. As the subjects aged, the detection rate increased gradually. A significant difference in the tonsillolith detection rate was found between the over and under 40-year-old groups (p < 0.0001). However, the detection rate of tonsilloliths was only 7.3% on panoramic radiographs. A significant correlation was observed between the detection rate of tonsilloliths on panoramic radiographs and CT number (Spearman r = 0.429), size, (Spearman r = 0.318), and number of tonsilloliths (Spearman r = 0.333)., Conclusion: The present results suggest that tonsilloliths are relatively more common than previously suggested. However, panoramic radiographs detect only a small percentage of palatine tonsilloliths. The low detection rates on panoramic radiographs might be related to the degree of calcification, size, and number of tonsilloliths.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of nitrogen-containing bisphosphonate (NBP) use. Many studies have shown that BRONJ is limited to the jawbone and does not occur in the other bones. We hypothesized that BRONJ is related to local bacterial iections and involves the innate immune system. To examine the relationship between BRONJ and innate immunity, we examined the effects of NBPs on macrophages, one of the important cell types in innate immunity. The expression of toll-like receptor-4 (TLR4) in cells after pretreatment with zoledronic acid (ZOL) did not considerably differ from that in untreated control cells. However, cytokine levels and nitric oxide (NO) production increased after pretreatment with ZOL. Furthermore, ZOL induced NF-κB activation by enhancing IκB-α degradation. Lipopolysaccharide (LPS)-induced apoptosis also increased after pretreatment with ZOL. This effect was mediated by a reduction of suppressor of cytokine signaling-1 (SOCS1), which is a negative regulator of myeloid differentiation primary response gene 88 (MyD 88)-dependent signaling. These results suggest that ZOL induced excessive innate immune response and proinflammatory cytokine production and that these processes may be involved in the bone destruction observed in BRONJ.

Purpose: The aim of the present study was to investigate the relation between magnetic resonance (MR) evidence of joint effusion and concentrations of proinflammatory cytokines, including interleukin (IL)-1β and IL-6, in washed-out synovial fluid samples obtained from patients with mandibular condyle fractures., Patients and Methods: Twenty-five joints in 23 patients with mandibular condyle fractures were examined. Computed tomography was used to determine the position of the fracture and MR examination was performed in all cases. Twenty-five joints underwent temporomandibular joint (TMJ) irrigation before surgical treatment for the fractures. The detection rates and concentrations of the tested cytokines were determined, and their relations to evidence of joint effusion and positions of the condylar fractures were analyzed., Results: Six TMJ fractures were found in the head, 10 in the upper neck, 4 in the lower neck, and 5 in the subcondyle. MR evidence of joint effusion was observed in 17 of 25 TMJs (68.0%). The detection rate and concentration of IL-6 were significantly higher in patients with MR evidence of joint effusion and those with high condylar fractures. Moreover, there was a correlation between joint effusion grade and IL-6 concentration., Conclusions: The present findings showed a correlation between MR evidence of joint effusion and concentration of IL-6 in washed-out synovial fluid samples collected from patients with mandibular condyle fractures. These results may provide support for arthrocentesis as a reasonable treatment modality for high condylar fractures., (Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: To elucidate the points that require attention when interpreting fluorine-18-labelled fluoro-2-deoxy-d-glucose ((18)F-FDG)/positron emission tomography (PET) images by demonstration of (18)F-FDG accumulation in various areas of the oral cavity other than primary lesions in patients with oral cancers., Methods: (18)F-FDG accumulations with a maximal standardized uptake value of over 2.5 in various areas of the oral cavity other than primary lesions were identified in 82 patients with oral cancers., Results: (18)F-FDG/PET-positive areas, excluding primary tumours, included the front intrinsic muscles of the tongue (89.0%), upper and lower marginal parts of the orbicularis oris muscle (64.6%), sublingual glands, palatine tonsil, pharyngeal tonsil, and lingual tonsil. In addition, some areas in the jaws also showed accumulation., Conclusions: In patients with oral cancers, areas of (18)F-FDG accumulation in the oral cavity should be precisely identified and appropriately diagnosed, because accumulations can be seen in areas other than the primary tumour.