Investigation of orthognathic surgery indicators-combination with index of orthognathic functional treatment needs (IOFTN) and maxillofacial morphometric analysis.

PURPOSE: The aim of this retrospective study was to determine orthognathic surgery indicators for Japanese patients with jaw deformities using both Index of Orthognathic Functional Treatment Needs (IOFTN) and maxillofacial morphometric analysis. SUBJECTS AND METHODS: The subjects were 89 patients treated with orthognathic surgery and 92 patients treated with orthodontic treatment alone, and were classified as class I, II, or III according to the ANB angle. Based on the results for IOFTN and the results of cephalometric analysis, the indication criteria for orthognathic surgery were examined. RESULTS: In IOFTN analysis, none of patients in the orthognathic surgery group were classified as category 1 or 2, while 48% of the patients in the orthodontic treatment group were classified as category 4 or 5. The results of the cephalometric analysis of patients in classified categories 4 and 5 showed that the orthognathic surgery group had significantly greater lateral mandibular deviation in Class I cases, significantly more severe degree of mandibular retrusion in Class II cases, and significantly more severe degree of mandibular prognathism in Class III cases. The results of the logistic regression analysis showed that IOFTN was a common variable as an indication criterion for orthognathic surgery, and several different variables were also selected from the cephalometric measurements in each group. CONCLUSION: IOFTN is a highly sensitive and useful indicator as a criterion for orthognathic surgery. However, in the choice of treatment strategy, maxillofacial morphometric analyses and the patient's desired goal are important.

Survey of the association between tooth extraction and development of medication-related osteonecrosis of the jaw in patients undergoing cancer treatment with bone-modifying agents.

OBJECTIVE: This study aimed to verify whether tooth extraction before the administration of bone-modifying agents (BMA) was effective in preventing the onset of medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: This retrospective study included patients with a history of receiving BMA for cancer treatment. The patients were classified into three groups based on the timing of tooth extraction: no tooth extraction before the onset of MRONJ, tooth extraction before the administration of BMA, and tooth extraction after the administration of BMA. The incidence of MRONJ was compared between the groups. Fisher's exact test and Bonferroni correction were used to test for differences in proportions between the three groups. RESULTS: The total number of subjects was 123. Twenty-four patients (19.5%) developed MRONJ. The incidence rates were 12.3% (10/81), 17.9% (5/28), and 64.3% (9/14) in the non-extraction group, the extraction before BMA administration group, and the extraction after BMA administration group, respectively, showing statistically significant differences between the extraction after BMA administration group and the non-extraction groups and between the extraction after BMA administration group and the extraction before BMA administration group (p < 0.001, p = 0.0049). On the other hand, there was no statistically significant difference in incidence between the non-extraction and the extraction before BMA administration group (p = 0.5274). CONCLUSIONS: Tooth extraction before the administration of BMA is effective in preventing the onset of MRONJ in patients receiving BMA for cancer treatment. Prevention of MRONJ development in patients receiving BMA for cancer treatment contributes to the maintenance of patients' quality of life.

Validation of a Cox prognostic model for tooth autotransplantation.

OBJECTIVES: This study aimed to validate our Cox proportional hazards prognostic model for autotransplantation of teeth with complete root formation using prognostic index (PI) and determine whether the prognosis can be predicted. PATIENTS AND METHODS: The Protocol group, as a training data set for validation, consisted of 259 autotransplanted teeth to create a PI using the Cox model, as described previously. The Pre-protocol group, as the first validation data set, consisted of 95 autotransplanted teeth treated without a protocol. The Post-protocol group, as the second validation data set, consisted of 61 autotransplanted teeth obtained after the establishment of the prognostic model. Because four prognostic factors, including history of root canal treatment (yes), number of roots (multirooted), source of donor tooth (maxillary tooth), and duration of edentulism (≥2.5 months), were selected as a Cox prognostic model, 16 patterns of PI were constructed. First, the autotransplantated teeth in the Protocol group were divided into low- and high-risk groups respectively according to the median of PI as the cutoff value. The survival curves of low- and high-risk groups were calculated using the Kaplan-Meier method and tested using the log-rank test. Then, in the Pre- and Post-protocol groups, all transplanted teeth were divided into low-and high-risk teeth by the median of PI and the survival curves of low- and high- risk teeth were analyzed statistically in a similar manner. RESULTS: The survival curves of the low- and high-risk groups diverged significantly in the Protocol and Post-protocol groups. In the Pre-protocol group, the curves of the low- and high-risk groups were separated, and the low-risk survival rate was improved. CONCLUSIONS: Our Cox prognostic model for autotransplantation of teeth with complete root formation was useful in predicting the prognosis by external validation using PI.

Masticatory muscle tendon-aponeurosis hyperplasia that was initially misdiagnosed for polymyositis: a case report and review of the literature.

BACKGROUND: Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a relatively newly identified clinical condition that manifests as trismus with a square-shaped mandible. Herein, we report a case of MMATH that was initially misdiagnosed for polymyositis due to trismus and simultaneous lower limb pain, with literature review. CASE PRESENTATION: A 30-year-old woman had a history of lower limb pain after exertion for 2 years. Initial physical examination had been performed at the Department of General Medicine in our hospital. There was also redness in the hands and fingers. Although polymyositis was suspected, it was denied. The patient visited our department for right maxillary wisdom tooth extraction. Clinical examination revealed that the patient had a square-shaped mandible. The maximal mouth opening was 22 mm. There was no temporomandibular joint pain at the time of opening. Furthermore, there was awareness of clenching while working. Panoramic radiography revealed developed square mandibular angles with flattened condyles. Computed tomography showed enlarged masseter muscles with high-density areas around the anterior and lateral fascia. Magnetic resonance imaging also showed thickened tendons and aponeuroses on the anterior surface and inside bilateral masseter muscles. Finally, the patient was diagnosed with MMTAH. Bilateral aponeurectomy of the masseter muscles with coronoidectomy and masseter muscle myotomy was performed under general anesthesia. The maximum opening during surgery was 48 mm. Mouth opening training was started on day 3 after surgery. Histopathological examination of the surgical specimen showed that the muscle fibers were enlarged to 60 µm. Immunohistochemistry testing for calcineurin, which was associated with muscle hypertrophy due to overload in some case reports, showed positive results. Twelve months after surgery, the mouth self-opening and forced opening were over 35 mm and 44 mm, respectively. CONCLUSIONS: Herein, we report a case of MMATH. Lower limb pain due to prolonged standing at work and overload due to clenching were considered risk factors for symptoms onset of MMATH.

Cholesterol Is a Regulator of CAV1 Localization and Cell Migration in Oral Squamous Cell Carcinoma.

Cholesterol plays an important role in cancer progression, as it is utilized in membrane biogenesis and cell signaling. Cholesterol-lowering drugs have exhibited tumor-suppressive effects in oral squamous cell carcinoma (OSCC), suggesting that cholesterol is also essential in OSCC pathogenesis. However, the direct effects of cholesterol on OSCC cells remain unclear. Here, we investigated the role of cholesterol in OSCC with respect to caveolin-1 (CAV1), a cholesterol-binding protein involved in intracellular cholesterol transport. Cholesterol levels in OSCC cell lines were depleted using methyl-ß-cyclodextrin and increased using the methyl-ß-cyclodextrin-cholesterol complex. Functional analysis was performed using timelapse imaging, and CAV1 expression in cholesterol-manipulated cells was investigated using immunofluorescence and immunoblotting assays. CAV1 immunohistochemistry was performed on surgical OSCC samples. We observed that cholesterol addition induced polarized cell morphology, along with CAV1 localization at the trailing edge, and promoted cell migration. Moreover, CAV1 was upregulated in the lipid rafts and formed aggregates in the plasma membrane in cholesterol-added cells. High membranous CAV1 expression in tissue specimens was associated with OSCC recurrence. Therefore, cholesterol promotes the migration of OSCC cells by regulating cell polarity and CAV1 localization to the lipid raft. Furthermore, membranous CAV1 expression is a potential prognostic marker for OSCC patients.

Anti-inflammatory activity of 2-methoxy-4-vinylphenol involves inhibition of lipopolysaccharide-induced inducible nitric oxidase synthase by heme oxygenase-1.

BACKGROUND: 2-Methoxy-4-vinylphenol (2M4VP) is a natural anti-inflammatory compound derived from red wine, but its underlying mechanism remains unclear. Heme oxygenase-1 (HO-1), an anti-inflammatory enzyme, inhibits NO gene expression, while nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor involved in HO-1 production, binds to the antioxidant response element (ARE) in the nucleus and promotes HO-1 transcription. Based on the hypothesis that the inhibitory effect of 2M4VP on NO production is mediated by HO-1, we examined the possible mechanism of the anti-inflammatory activity of 2M4VP in this study. MATERIALS AND METHODS: The anti-inflammatory activity of 2M4VP was analyzed by Griess method, ELISA, qPCR, and Western blotting using LPS-treated macrophage lineage RAW264.7 cells. The impact of 2M4VP on the Nrf2/ARE pathway was also analyzed using immunocytochemistry and an ARE luciferase reporter using HEK293 cells. RESULTS: The results showed that 2M4VP reduced the production of LPS-induced NO and inducible nitric oxidase synthase (iNOS). In addition, 2M4VP increased the expression of HO-1, while pretreatment with the Nrf2 inhibitor ML385 downregulated HO-1 expression. 2M4VP induced Kelch-like ECH-associated protein 1 (Keap1) degradation. Furthermore, it promoted Nrf2 nuclear translocation and increased luciferase activity by binding to the ARE. CONCLUSIONS: 2M4VP induces Keap1 degradation and promotes Nrf2 nuclear translocation. Activation of Nrf2/ARE pathway enhances HO-1 expression and leads to iNOS inhibition for anti-inflammatory function.

A three-dimensional investigation of mandibular deviation in patients with mandibular prognathism.

BACKGROUND: Craniofacial disharmony in cases of jaw deformity associated with abnormal lateral deviation of the jaw mostly involves both the maxilla and mandible. However, it has been still difficult to capture the jaw deviation aspect in a 3-dimensional and quantitative techniques. In this study, we focused on 3-dimensional mandibular morphology and position of the condylar head in relation to the base of the skull in patients with mandibular prognathism, one of the most common jaw deformities. We used cluster analysis to quantify and classify deviation and clarified its characteristics. We also investigated the degree of correlation between those findings and menton (Me) deviation measured on frontal cephalograms, which is a conventional indicator of jaw deformity. RESULTS: Findings obtained from 100 patients (35 men, 65 women) were classified into the following three groups based on mandibular morphology and condylar position relative to the skull base. Then, reclassification using these parameters enabled classification of cluster analysis findings into seven groups based on abnormal jaw deviation characteristics. Comparison among these seven groups showed that the classification criteria were ramus height, mandibular body length, distance from the gonion to the apex of the coronoid process, and the lateral and vertical positions of the mandible. Weak correlation was also found between Me deviation on frontal cephalograms and each of the above parameters measured on 3D images. CONCLUSIONS: Focusing on mandibular morphology and condylar position relative to the skull base in patients with mandibular prognathism, we used cluster analysis to quantify and classify jaw deviation. The present results showed that the 3D characteristics of the mandible based on mandibular morphology and condylar position relative to the skull base can be classified into seven groups. Further, we clarified that Me deviation on frontal cephalograms, which has been used to date, is inadequate for capturing jaw deviation characteristics.

Evaluation of oral health-related quality of life in patients with temporomandibular disorders.

OBJECTIVE: To evaluate oral health-related quality of life (OHRQoL) in patients with temporomandibular disorders (TMDs). METHODS: Subjects included 56 patients diagnosed with TMD. Control subjects consisted of 30 individuals without temporomandibular joint symptoms. OHRQoL was evaluated using the Japanese version of the Oral Health Impact Profile (OHIP-J54) before and 4 months after treatment. RESULTS: Total score and all subscale scores of the OHIP-J54 in patients before treatment were significantly higher than those of the control subjects and were significantly improved after treatment, except for social disability. Gender and NRS pain scores had statistically significant effects on OHRQoL, which was low in females and patients with severe pain. CONCLUSION: OHIP-J54 appeared to be useful for understanding psychological and social problems as a screening tool and for assessing the extent of changes in the well-being of patients with TMD.

Oral appliance therapy for obstructive sleep apnea in multiple system atrophy with floppy epiglottis: a case series of three patients.

PURPOSE: A recent study demonstrated that continuous positive airway pressure (CPAP) may exacerbate obstructive sleep apnea (OSA) in patients with multiple system atrophy (MSA) and a floppy epiglottis (FE) as the CPAP promotes downward displacement of the epiglottis into the laryngeal inlet. In this case series, we examined the effectiveness of an oral appliance (OA) for treating OSA in three patients with MSA and an FE. METHODS: Patients with MSA were demonstrated to have an FE on fiberoptic laryngoscopy under sedation using intravenous propofol. The therapeutic intervention was fitting an OA. Polysomnography (PSG) was performed subsequently with the OA in place. RESULTS: In three patients with MSA, some parameters used to assess the severity of OSA improved with an OA. Both apnea-hypopnea index (AHI) and arousal index (ArI) decreased while wearing the OA in two cases while in the third case, apnea index (AI) and cumulative time at peripheral oxygen saturation (SpO2) below 90% (CT90) decreased, but AHI and ArI increased. The only side effects were transient TMJ discomfort, masseter muscle pain, and tooth discomfort. CONCLUSION: OA therapy using a two-piece type mandibular advancement device (MAD) may be a useful treatment intervention for patients with OSA who have MSA and FE.

Changes in nutritional status of patients with jaw deformities due to orthognathic surgery.

OBJECTIVE: In orthognathic surgery, it is important to carefully manage peri-operative nutrition because maxillomandibular fixation and problems such as swelling and pain after surgery may make it difficult to eat normally and may prevent adequate nutrition. This study investigated the changes in nutritional status of patients with jaw deformities due to orthognathic surgery. STUDY DESIGN: The subjects were 155 jaw deformity patients, who underwent orthognathic surgery. The nutritional status was evaluated using anthropometry immediately before and 10 days after surgery and clinical laboratory results and the controlling nutritional status (CONUT) score before surgery and immediately, 1 week and >6 months after surgery. We investigated the relationship among the nutritional status, surgical procedures, and dietary intake in patients who underwent orthognathic surgery. RESULTS: The surgical procedure time and amount of bleeding were significantly greater as the surgical procedure became more complex. All of the laboratory values and CONUT scores were significantly decreased immediately after surgery and then increased over time, recovering to the same level as before surgery except for serum albumin at >6 months after surgery. CONCLUSIONS: Nutritional management is considered as one of the key factors for the better and faster recovery after the orthognathic surgery.

Prognostic value of preoperative systemic inflammatory response as a prognostic indicator in patients with early-stage oral squamous cell carcinoma.

To determine the usefulness of lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and inflammatory response biomarker (IRB) score for predicting disease-specific survival and delayed cervical lymph node metastasis in early-stage oral squamous cell carcinoma (OSCC). We retrospectively analyzed 72 patients with early-stage OSCC. Receiver operating characteristic curve analysis was used to determine the cutoff values for LMR, NLR, and PLR. IRB score was determined as follows: high LMR, high NLR, and low PLR, which were each rated as 1. These scores were added to obtain IRB score (range: 0-3). From univariate analysis, gender, poor mode of invasion, and high IRB score were identified as significant risk factors for disease-specific survival. However, there were no independent factors for poor prognosis in multivariate analysis. On the other hand, for delayed cervical lymph node metastasis, poor mode of invasion, low LMR, high NLR, high PLR, and high IRB score were identified as significant risk factors from univariate analysis, and in multivariate analysis, poor mode of invasion and high IRB score were confirmed as independent risk factors. IRB score and mode of invasion are potentially independent risk factors for delayed cervical lymph node metastasis in early-stage OSCC.

Examination of factors affecting condylar bone changes following surgical-orthodontic treatment.

OBJECTIVE: To identify factors affecting condylar bone changes following surgical-orthodontic treatment. METHODS: A total of 200 patients with dentofacial deformities were classified into skeletal Classes I, II, and skeletal Class III groups consisting of 61 and 139 subjects, respectively. Temporomandibular joints (TMJs) were evaluated using clinical findings and computed tomography images before treatment, immediately before surgery, and 6 months after surgery. RESULTS: Condylar bone changes occurred at a significantly higher rate after surgery in both groups. Factors related to condylar bone changes following surgical-orthodontic treatment included skeletal Class I or II, disc displacement, and condylar bone changes before treatment. There were three cases with condylar bone changes after surgery that were diagnosed with condylar resorption and skeletal Class II and anterior disc displacement before surgery. CONCLUSION: Condylar resorption could occur when the load on the condyle increases after orthognathic surgery and exceeds the permissible limit.

Novel cytological model for the identification of early oral cancer diagnostic markers: The carcinoma sequence model.

Most oral squamous cell carcinomas (OSCCs) arise from a premalignant lesion, oral epithelial dysplasia; however, useful markers for the early detection of OSCC are lacking. The present study aimed to establish a novel experimental model to observe changes in the sequential expression patterns of mRNAs and proteins in a rat model of tongue cancer using liquid-based cytology techniques. Cytology specimens were collected at 2, 5, 8, 11, 14, 17 and 21 weeks from rats treated with 4-nitroquinoline 1-oxide to induce tongue cancer. The expression of candidate biomarkers was examined by performing immunocytochemistry and reverse transcription-quantitative PCR. The percentage of positively stained nuclei was calculated as the labeling index (LI). All rats developed OSCC of the tongue at 21 weeks. The mRNA expression levels of bromodomain protein 4 (Brd4), c-Myc and Tp53 were upregulated during the progression from negative for intraepithelial lesion or malignancy to squamous cell carcinoma (SCC). Brd4- and c-Myc-LI increased in low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion and SCC specimens. p53-LI was significantly increased in SCC specimens. This novel experimental model allowed the observation of sequential morphological changes and the expression patterns of mRNAs and proteins during carcinogenesis. Combining immunocytochemistry with cytology-based diagnoses may potentially improve the diagnostic accuracy of OSCC.

Migration and phenotype switching of macrophages at early-phase of bone-formation by secretomes from bone marrow derived mesenchymal stem cells using rat calvaria bone defect model.

BACKGROUND/PURPOSE: Conditioned media of cultured mesenchymal stem cells (MSCs) contain numerous kinds of secretomes such as cytokines and chemokines. We previously reported that conditioned media of bone marrow-derived MSCs (MSC-CM) promote bone formation. Recently, macrophage phenotype switching from the pro-inflammatory M1 type to the anti-inflammatory M2 type has been reported to be an important phenomenon during tissue regeneration. Some studies reported that this phenotype switching is regulated by secretomes. In this study, macrophage phenotype during bone formation by MSC-CM was investigated. MATERIALS AND METHODS: Human MSCs (hMSCs) were cultured in serum-free medium and the collected medium was defined as MSC-CM. Macrophage-related gene expressions in hMSCs cultured with MSC-CM were evaluated by quantitative real-time polymerase chain reaction. MSC-CM was implanted and the evaluations by micro-CT and immunohistochemistry were performed using a rat the calvaria bone defect model. RESULTS: Two and four weeks after implantation, the MSC-CM group demonstrated enhanced bone regeneration. Gene expressions of C-C motif chemokine 2 (CCL2), colony-stimulating factor 2 (CSF2) and CD163 was significantly upregulated in cells exposed to MSC-CM. Immunohistochemical staining revealed that iNOS-positive M1 macrophages were reduced, while CD204-positive M2 macrophages were increased in the MSC-CM group at 72 h after implantation, and the M2/M1 ratio increased only in the MSC-CM group. CONCLUSION: MSC-CM enhances macrophage migration and induces M1 to M2 type macrophage switching at an early stage of osteogenesis. Such phenotype switching provides a favorable environment for angiogenesis, cellular migration, and osteogenesis and contributes to MSC-CM-induced early bone formation.

The use of an ultrasonic curettage device in orthognathic surgery decreases surgery-related blood loss.

Objective: This study aimed to compare the use of a powered instrument (PI) and ultrasonic curettage device (ULCD) with intraoperative blood loss (IOBL), drain volume (DV), calculated blood loss (CBL), and hidden blood loss (HBL) in orthognathic surgery. Methods: We included 163 patients who underwent bimaxillary surgery in our department. CBL was calculated from the preoperative and postoperative hemoglobin levels using the "hemoglobin balance method." CBL is an indicator of the amount of perioperative blood loss. HBL was calculated by subtracting IOBL and DV from CBL. Results: The PI group consisted of 61 patients (17 males and 44 females, age: 24.9 ± 9.5 years), and the ULCD group consisted of 102 patients (40 males and 62 females, age: 23.1 ± 7.8 years). In the PI group, the median IOBL, DV, CBL, and HBL were 540.0 (interquartile range [IQR] 380.0-670.0), 113.0 (IQR 77.0-147.0), 1000.0 (IQR 751.4-1248.6), and 285.8 (IQR 151.0-476.4) ml, respectively. In the ULCD group, the median IOBL, DV, CBL, and HBL were 327.5 (IQR 200.0-455.0), 105.5 (IQR 75.3-136.0), 759.5 (IQR 594.9-944.2), and 294.2 (IQR 120.8-456.9) ml, respectively. IOBL and CBL were significantly reduced with ULCD use, but no significant differences were observed in DV and HBL. Conclusions: This study showed that IOBL decreased with ULCD use, resulting in a decrease in CBL. Conversely, bleeding parameters (DV and HBL), which reflect the amount of bleeding that occurs after wound closure, did not show a decrease with ULCD use.

Melanotic neuroectodermal tumor of infancy in the mandible: A case report.

RATIONALE: Melanocytic neuroectodermal tumor of infancy (MNTI) is a rare benign pigmented neoplasm that arises from the neural crest and has an aggressive growth pattern. It is predominantly seen in infants under 1 year of age, and the most common site of involvement is the maxilla. The currently accepted treatment is removal by surgical resection. Herein, we report a case of MNTI that involved the anterior alveolar ridge of the mandible in a 6-month-old infant. PATIENT CONCERNS: A case of a 6-month-old male child with a huge mass in the anterior alveolar ridge of the mandible. DIAGNOSIS: The tumor was diagnosed using histopathological and immunohistochemical techniques on the biopsy specimen obtained following incisional biopsy. Based on the findings, a final diagnosis of MNTI was established. INTERVENTIONS: Radical resection of the tumor was performed, after determining the extent of resection by referring to the mandibular 3D model created using the pre-operative CT data. OUTCOMES: The postoperative course was uneventful, and no recurrence has been observed to date for more than 4 years after surgery. LESSONS: This case emphasizes that early diagnosis and radical surgery are critical to the effective treatment, as MNTI exhibits rapid and destructive growth. It also requires careful and close follow-up because of high recurrence rates.

Crosstalk between oral squamous cell carcinoma cells and cancer-associated fibroblasts via the TGF-ß/SOX9 axis in cancer progression.

Cancer-associated fibroblasts (CAFs) have important roles in promoting cancer development and progression. We previously reported that high expression of sex-determining region Y (SRY)-box9 (SOX9) in oral squamous cell carcinoma (OSCC) cells was positively correlated with poor prognosis. This study developed three-dimensional (3D) in vitro models co-cultured with OSCC cells and CAFs to examine CAF-mediated cancer migration and invasion in vitro and in vivo. Moreover, we performed an immunohistochemical analysis of alpha-smooth muscle actin and SOX9 expression in surgical specimens from 65 OSCC patients. The results indicated that CAFs promote cancer migration and invasion in migration assays and 3D in vitro models. The invading OSCC cells exhibited significant SOX9 expression and changes in the expression of epithelial-mesenchymal transition (EMT) markers, suggesting that SOX9 promotes EMT. TGF-ß1 signalling inhibition reduced SOX9 expression and cancer invasion in vitro and in vivo, indicating that TGF-ß1-mediated invasion is dependent on SOX9. In surgical specimens, the presence of CAFs was correlated with SOX9 expression in the invasive cancer nests and had a significant impact on regional recurrence. These findings demonstrate that CAFs promote cancer migration and invasion via the TGF-ß/SOX9 axis.

Other iatrogenic immunodeficiency-associated lymphoproliferative disorders in the oral cavity: a clinicopathologic study of 4 cases and literature review.

OBJECTIVES: Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OI-LPD) have been reported as one of the adverse effects of immunosuppressive therapy. The aim of this study was to describe the clinicopathologic and immunohistochemical features of OI-LPD in the oral cavity. STUDY DESIGN: Immunohistochemistry was performed to describe the immunohistochemical features in our 4 cases. The results were analyzed along with 62 cases of oral OI-LPD in the English and Japanese literature to define clinical and pathologic characteristic features. RESULTS: In our immunohistochemical analysis, Epstein-Barr virus (EBV)-positive OI-LPD showed a higher percentage of mouse double minute 2-positive cells than EBV-negative samples. A literature survey revealed that OI-LPD (including the present cases) arises primarily in the gingiva, followed by the tongue, and usually occurs with a male-to-female ratio of 1:1.9. The rate of EBV positivity was 93.8%. Further, 31 of 66 patients had osteonecrosis of the jaw and 24 of 31 patients had taken multiple immunosuppressive drugs in combination. CONCLUSIONS: We can therefore conclude that the overexpression of mouse double minute 2 in OI-LPD is associated with EBV infection, and the combination of multiple immunosuppressive drugs may be a risk factor for osteonecrosis of the jaw.

HEATR1, a novel interactor of Pontin/Reptin, stabilizes Pontin/Reptin and promotes cell proliferation of oral squamous cell carcinoma.

Pontin and Reptin are closely related proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They form a hetero-oligomeric complex, Pontin/Reptin, which is involved in protein stability and assembly of the protein complexes as a molecular chaperone. Overexpression of Pontin and Reptin in tumor cells has been reported and is implicated in the development of various cancers. However, the molecular mechanism of Pontin/Reptin function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we identify HEAT repeat-containing protein 1 (HEATR1) as a novel binding factor of Pontin/Reptin. Functionally, HEATR1 stabilizes Pontin/Reptin and positively regulates OSCC cell proliferation by activating mTOR and pre-rRNA synthesis. We also find that HEATR1 expression is markedly upregulated in tumor region of OSCC tissue. Hence, we propose that HEATR1 is involved in the regulation of mTOR and ribosome biogenesis as a potential protein stabilizer of Pontin/Reptin in OSCC.

Conditioned medium from mesenchymal stem cells improves condylar resorption induced by mandibular distraction osteogenesis in a rat model.

Condylar resorption (CR) after surgical orthognathic treatment is defined as dysfunctional remodeling of the temporomandibular joint manifested by morphological changes with decreased condylar head volume that cause occlusal and esthetic changes. Although both conservative and surgical treatment strategies have been employed for the treatment of CR, effective procedures have not been established till date. In this study, the effects of MSC-CM on CR were investigated. Bone marrow-derived MSCs of rats (rMSCs) were cultured until 80% confluent, cultured in serum-free conditioned medium for 48 h; the collected medium was defined as MSC-CM. Osteogenesis, chondrogenesis, and angiogenesis-related gene expression in rMSCs cultured with MSC-CM was evaluated by quantitative real-time polymerase chain reaction. A rat CR model was used for animal studies, in which CR occurred after mandibular distraction osteogenesis for 10 days. MSC-CM was injected via the tail vein and quantitative and qualitative evaluations were performed by micro-computed tomography (micro-CT) and histology. MSC-CM enhanced osteogenesis-, chondrogenesis-, and angiogenesis-related gene expression in rMSCs. Micro-CT showed CR in control groups; however, it was observed to be improved in the MSC-CM group. Histologically, an enlarged cartilage layer was seen in the MSC-CM group, while cartilage layers had almost thinned or disappeared in control groups. These results indicate that MSC-CM improved CR.