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The objective was to evaluate stiffness as a prognostic factor for tongue squamous cell carcinoma (TSCC).This retrospective study included 55 patients with pathologic stage pT1 or T2 TSCC with muscle-layer invasion who underwent preoperative strain elastography of the tongue, followed by surgery, as the primary treatment modality at our cancer center. The stiffness of TSCC was semi-quantified as the ratio of the strain value of a non-tumor site to the strain value of the tumor site (strain ratio [SR]) using ultrasound strain elastography findings.SR cutoff values that maximized the significance of the difference for prognosis of delayed cervical lymph node metastasis (DCLNM) and overall survival (OS) were 7.10 and 7.49, respectively. In univariate analysis, SR, age, depth of invasion, pT stage, and perineural invasion were significant risk factors for DCLNM, whereas SR, sex, and DCLNM were identified as having an association with OS. In multivariate analysis, SR was a significant risk factor for DCLNM (hazard ratio [HR] = 3.102; P = .021) and a non-significant but relevant risk factor for OS (HR = 8.774; P = .073). Age also had an association with OS (HR = 0.382; 95% CI 0.127-1.152; P = .088).Tongue stiffness is a prognostic factor in patients with pT1/T2 TSCC with muscle-layer invasion. SR values7.10 indicate a poor prognosis, thereby warranting a strict follow-up regimen in these cases.

Polyrotaxanes (PRXs) containing acetylated α-cyclodextrins exhibit a temperature-dependent phase transition in aqueous solutions across their lower critical solution temperature (LCST) of approximately 26.6 °C. To gain insights into the interactions of acetylated PRXs (Ac-PRXs) with biological components, thermoresponsive supramolecular surfaces were prepared by coating tissue culture polystyrene (TCPS) surfaces with Ac-PRX triblock copolymers, and their surface properties across the LCST were evaluated. The wettability and protein adsorption of Ac-PRX-coated surfaces changed significantly between 10 and 37 °C, whereas the uncoated TCPS and unmodified PRX-coated surfaces did not alter the wettability and protein adsorption at 10 and 37 °C. The adhesion, proliferation, morphology, and adhesion strength of NIH/3T3 cells on Ac-PRX-coated surfaces were found to be similar to those of the uncoated and unmodified PRX-coated surfaces. However, the adhesion strength of NIH/3T3 cells on Ac-PRX-coated surfaces decreased drastically at 10 °C. Consequently, the cells spontaneously detached from the Ac-PRX-coated surfaces without enzymatic treatment. Additionally, when incubating confluent cells at 10 °C, the cells detached from Ac-PRX-coated surfaces as cell sheets while retaining extracellular matrix proteins. The findings of this study provide new directions for the design of thermoresponsive supramolecular biointerfaces for applications in bioseparation and cell manipulation.

Schwannomas are benign tumours that originate from the Schwann cells of the nerve. Despite the frequency of their occurrence in the head and neck, data relating to their clinicopathological features in the region are limited. This study reviews the clinicopathological characteristics and specific pathology of ancient (degenerative) change in 40 cases in the oral and maxillofacial region. Medical records were reviewed of the 40 cases treated at Tokyo Medical and Dental University Hospital Faculty of Dentistry between 2000 and 2020. The most frequently involved site was the tongue, and the average tumour size was 13.2 mm. Degenerative changes were observed in eight cases. All tumours were completely excised through biopsy or local excision, and no recurrence was observed on clinical follow up. Statistical analyses revealed significant associations (p 0.05) between ancient change and tumour size, and between ancient change and the apparent diffusion coefficient (ADC) value derived from diffusion-weighted magnetic resonance imaging (MRI). Analysis suggests that schwannoma progresses over a long period and subsequently undergoes secondary ancient changes. Pathological events such as cystic formation and haemorrhage that are associated with ancient changes, cause hypocellularity and lead to high ADC values. These values may indicate ancient change and should be considered when distinguishing schwannoma from other lesions.

Objectives Cysts of the mandible are common and are often found clinically in oral surgery. Marsupialization for relatively large cystic lesions may be performed to reduce the size of the lesion and to obtain a histopathological diagnosis. For cystic lesions of the mandible, the effect of marsupialization has many advantages, such as a reduction in lesion size, the avoidance of mental nerve palsy, and preservation of the teeth. It is still unclear whether there is a difference in the reduction rate based on patient age and pathology (dentigerous cyst, odontogenic keratocyst, radicular cyst, ameloblastoma (unicystic type)) and initial size of the lesion. Methods The subjects included 55 patients with cystic lesions with a major axis of 3 cm or greater (16 dentigerous cysts, 20 odontogenic keratocysts, 7 radicular cysts, and 12 ameloblastoma) who underwent treatment at our department. Using simulation software (ProPlanCMF®), the volume of the lesion was extracted from the CT data before and after the marsupialization, and the three-dimensional reduction rate before and after marsupialization was calculated. Results No significant difference was observed between the subgroups in terms of histopathological diagnosis, patient age or size of lesion. Although the effect of marsupialization on cystic lesions with a major axis of 3 cm or more showed a significant difference between 3.0 months and 4.5 months, the difference was not significant between 4.5 months and 6.0 months. Conclusions An indication for the enucleation timing after marsupialization is 4.5 months when the rate of decrease after fenestration slows down.

Owing to a high recurrence rate, radical jaw resection is regarded as the first choice of treatment for odontogenic myxoma. However, there have been several reports on the effectiveness of conservative surgical treatment preserving inferior alveolar nerve for odontogenic myxoma of the mandible. A 37-year-old woman presented with a complaint of pain around her mandibular left third molar. Odontogenic myxoma was diagnosed by using biopsy. The tumor occupied a part of the cortical bone and contained the inferior alveolar nerve. We performed enucleation and curettage, which preserved the inferior alveolar nerve. Ten years after the treatment, there were no symptoms of recurrence or nerve paralysis. Here, we discuss the conservative treatment of odontogenic myxoma, focusing on inferior alveolar nerve preservation.

A dermoid cyst is lined by an epidermis-like epithelium with dermal adnexal structures contained within the cyst wall. The “sac of marbles” sign is a characteristic image finding of a dermoid cyst but its pathogenesis is unknown. In this report, we aim to elucidate the cause of the sac of marbles using immunohistological studies. We report the case of a 39-year-old man with a dermoid cyst in the floor of the mouth with a “sac of marbles” sign that was revealed by magnetic resonance imaging. We analyzed the histology of the sac of marbles in dermoid cysts and performed an immunohistological analysis of keratin subtypes. Histopathologically, the sac of marbles contained a spherical accumulation of anucleated epithelial cells; immunohistochemistry revealed that it was positive for keratin1 and keratin 10 and was negative for keratin 15 and keratin 17, demonstrating the same direction of differentiation as the cyst-lining epithelium. The results of this study show that the sac of marbles originates from denatured keratin derived from the lining epithelium.

Free cholesterol acts as an endogenous agonist for estrogen-related receptor α (ERRα), a nuclear receptor that regulates osteoclastogenesis. Because stimulation of macrophages with receptor activator of nuclear factor κB ligand (RANKL) induces an overload of free cholesterol and activates ERRα, we hypothesized that direct removal of cellular cholesterol would suppress osteoclastogenesis. In this study, the effect of 2-hydroxypropyl β-cyclodextrin (HP-β-CD), a highly water-soluble cyclic glucopyranose, and β-CD-threaded polyrotaxanes (PRXs), supramolecular polymers designed to release threaded β-CDs in acidic lysosomes, on RANKL-induced cholesterol overload and osteoclast differentiation of murine macrophage-like RAW264.7 cells were investigated. PRXs suppressed RANKL-induced cholesterol overload. Additionally, RANKL-induced osteoclast differentiation of RAW264.7 cells was inhibited by PRXs. In contrast, HP-β-CD did not reduce cholesterol levels or inhibit osteoclast differentiation in RAW264.7 cells. Gene expression analysis of osteoclast markers suggested that PRXs suppress only the early stage of osteoclast differentiation, as PRXs cannot be internalized into multinucleated osteoclasts. However, modification of PRXs with cell-penetrating peptides facilitated their cellular uptake into multinucleated osteoclasts and inhibited osteoclast maturation. Thus, PRXs are promising candidates for inhibiting osteoclast differentiation by suppressing cholesterol overload and may be useful for treating osteoporosis or other bone defects caused by the overactivity of osteoclasts.

Purpose To retrospectively evaluate skeletal stability after Le Fort I maxillary impaction surgery and mandibular autorotation without bilateral sagittal split osteotomy (BSSO) in high-angle class II patients. Materials and methods Seven female high-angle class II patients who underwent maxillary impaction surgery and mandibular autorotation without bilateral sagittal split osteotomy were included in this study. Surgical changes and relapse were measured on lateral cephalograms taken preoperatively and at 1 month, 6 months and 1 year postoperatively. Results The horizontal movement of the maxilla at point A was 5.8 ± 3.3 mm backward, and the upward movement at the posterior nasal spine was 3.3 ± 1.4 mm. The mean horizontal change at point A during the 1-year follow-up period was 0.1 ± 0.2 mm, and the vertical change at posterior nasal spine was 0.2 ± 1.3 mm, which were not statistically significant. The horizontal surgical change at point B was 4.0 ± 1.8 mm forward and the vertical surgical change at point B was 4.7 ± 1.8 mm upward. Postoperative relapse was 10.9% and 13.7% in the horizontal and vertical directions, respectively. Conclusions Le Fort I maxillary impaction surgery with mandibular autorotation may be 1 of the suitable procedures for high-angle class II patients.

This study aimed to estimate the disc status in intermittent closed lock (ICL) and permanent closed lock (CL) temporomandibular disorders (TMDs) to test the hypothesis that the disc morphology and degree of anterior disc displacement affect the outcomes of these disorders.All patients were clinically examined according to the Diagnostic Criteria for Temporomandibular Disorders Axis I protocol, and magnetic resonance imaging (MRI) confirmed ICL and CL. Fifty-six joints of 56 patients with ICL and 110 joints of 110 patients with acute CL with a locking period of less than 3 months were included. Patients with acute CL were further classified into two groups: those with CL that could be successfully manipulated (CLs group) and those with acute CL without the possibility of unlocking (CLu group). MRI was used to assess the degree of anterior displacement, lateral displacement of the disc, disc deformity, and joint effusion. MRI findings were compared among the joints in the ICL, CLs, and CLu groups.The degree of anterior displacement and disc deformity prevalence significantly differed among the ICL, CLs, and CLu groups. No significant intergroup differences were observed in terms of lateral displacement or joint effusion.These results suggest that anteriorly displaced discs and deformation of discs associated with TMD progression affect disc reducibility.

Polyetheretherketone (PEEK) is a candidate material for bone implants as an alternative to metals. However, PEEK exhibits poor osseointegration and low endothelial compatibility. This study demonstrates the phototethering of collagen onto PEEK surfaces to facilitate osteoblastic and vascular endothelial performance. In particular, collagen with methacryloyl groups is covalently tethered to the PEEK surface via surface-initiated photopolymerization. This process is simpler than the conventional method of collagen-tethering and can be extended to the surface-patterning treatment of collagen. The collagen is confirmed to be tethered to the PEEK surface using attenuated total reflection Fourier transform infrared measurements, bicinchoninic acid assays, and atomic force microscopic observations. When human bone marrow-derived mesenchymal stem cells (HbmMSCs) are cultured on collagen-tethered PEEK (COL-PEEK) surfaces, the cells favorably adhere and proliferate. After inducing osteogenic differentiation, the cells on the COL-PEEK surfaces show higher expression levels of osteoblast-related genes and mineralization than those on the PEEK surface. Moreover, the tethering of collagen greatly improves endothelial proliferation. The COL-PEEK surfaces promotes endothelial networking in coculture with HbmMSCs. These results suggest that COL-PEEK is highly compatible with both osteoblasts and vascular endothelial cells. COL-PEEK is a promising implant that induces osteogenesis and angiogenesis to repair bone tissues.

To evaluate the relationship between the changes in condylar volume and maxillofacial skeletal morphology according to sex as well as the relationship between condylar volume reduction and skeletal relapse in patients who underwent orthognathic surgery.Ninety-five patients were categorized into skeletal Class III, Class II, and facial asymmetry groups. Computed tomography scans taken preoperatively and at 1 year postoperatively were used for quantitative measurement.Postoperative condylar volume was reduced in both the Class II group and the deviated side of the asymmetry group. Both female and Class II deformity were significant predictors of postoperative reduction in the condylar volume. There was a significant correlation between skeletal relapse and postoperative change in condylar volume in the Class II group.Postoperative condylar resorption may be associated with preoperative maxillofacial skeletal morphology and sex and also with skeletal relapse in the Class II group.

BackgroundMaxillary gingival squamous cell carcinoma (MGSCC) occurs rather infrequently, compared to tongue and mandibular gingival carcinomas, among the cancers of the oral cavity. Therefore, significant numbers of MGSCC cases have not been statistically analysed. The aim of this study is to clarify the prognostic factors for MGSCC. MethodsWe performed the statistical analysis of 90 MGSCC cases primarily treated in our department from 1999 to 2014. ConclusionsThe patients (male: 36, female: 54) were aged between 38 and 93 years, and the mean age was 68.7 years. The number of patients in each tumour stage according to the TNM classification was as follows: T1: 15 cases, T2: 32 cases, T3: 13 cases, and T4: 30 cases. Forty-two patients were treated only by surgery, 5 only by radiotherapy, 3 by preoperative radiotherapy and surgery, and 40 patients were treated by combination therapy with preoperative chemoradiotherapy and surgery. Neck dissections were performed in 40 cases including 29 cases (11 primary and 18 secondary cases) of histopathologically diagnosed lymph node metastases. Extranodal extension was found in 74.3% cases with metastatic lymph nodes. The 5-year overall survival rate was 81.9%. In univariate analysis, the site of occurrence, stage of tumour, lymph node metastasis, and treatment contributed to the 5-year survival rate. Multivariate analysis demonstrated that the site of occurrence (posterior region) was an independent prognostic factor. Seventeen deaths occurred due to the primary disease, while three deaths were caused by other diseases. ConclusionThe posterior region cancers, according to the classification based on site of occurrence, were independent predictors of poor 5-year overall survival rate.

Objective The objective of this study was to investigate the prognostic effects of clinical and histologic findings in patients with mucoepidermoid carcinoma (MEC) of minor salivary glands. Study Design This retrospective clinical review included 63 patients (30 males, mean age 52.8 years) with minor salivary gland MEC treated at our hospital from 1994 to 2019. Overall survival (OS) or disease-free survival was determined using the Kaplan-Meier limit method. Correlations between different factors and survival rates were assessed using chi-square tests. Results The 10-year OS rate was 91.2%. Low- or intermediate-grade MEC had a good prognosis regardless of the surgical margin, whereas high-grade MEC had a poor 10-year OS rate (64.2%). Ten patients developed recurrence or metastasis after primary surgical resection, of whom 6 were diagnosed with a high-grade tumor. The most frequently affected site was the palate, whereas the mandibular gingiva was the most commonly affected site during recurrence. Of 4 patients who received chemotherapy and/or radiotherapy postsurgery, 2 had local recurrence and/or neck lymph node metastasis and 1 died from MEC. Conclusion Patients with low- or intermediate-grade MEC exhibited satisfactory survival after surgery. In patients with high-grade tumors, it has been suggested that survival rates are poor and do not improve following adjuvant therapy.

Engineered cartilage tissue from differentiated mesenchymal stem cells (MSCs) can generate bone in vivo through endochondral ossification (ECO). This ECO-mediated approach has the potential to circumvent the severe problems associated with conventional MSC-based bone tissue engineering techniques that lack mechanisms to induce angiogenesis. Hyaluronic acid (HA) is a key component in the cartilage extracellular matrix. However, the ECO-supporting properties of HA remain largely unclear. This study aimed to compare the ability of HA and collagen hydrogels to support in vitro differentiation of MSC-based hypertrophic cartilage tissues and to promote endochondral bone formation in vivo. Following the chondrogenic and hypertrophic differentiation in vitro, both HA and collagen constructs accumulated sulfated glycosaminoglycan (sGAG) and type 1, type II, and type X collagen. However, HA hydrogels exhibited a more uniform distribution of sGAG, type 1 collagen, type X collagen, and osteocalcin proteins; in addition, the cells embedded in the hydrogels had more rounded cell morphologies than those in the collagen constructs. At week 5 of in vitro culture, two to three constructs were implanted into a subcutaneous pocket in nude mice and harvested after 4 and 8 weeks. Both HA and collagen constructs promoted endochondral bone formation with vascularization and bone marrow development; however, the HA constructs fused to form integrated bone tissues and the bone marrow developed along the space between the two adhered grafts in all implanted pockets (n = 5). In the collagen constructs, the integration was observed in 40% of the pockets (n = 5). Microcomputer CT analysis revealed that the bone volume of HA constructs was larger than that of collagen constructs. In conclusion, compared to collagen hydrogels, HA hydrogels had superior potential to generate integrated bone with vascularization and bone marrow development. This study provides valuable insights for applying ECO-mediated bone tissue engineering approaches for the repair of critical-sized bone defects.

Background Hypopharyngeal cancer is a relatively rare malignancy with poor prognosis. Current chemotherapeutic algorithm is still far from personalized medicine, and the identification of the truly active therapeutic biomarkers and/or targets is eagerly awaited. Methods Venturing to focus on the conventional key chemotherapeutic drugs, we identified the most correlative genes (and/or proteins) with cellular sensitivity to docetaxel (TXT), cisplatin (CDDP) and 5-fluorouracil (5-FU) in the expression levels, through 3 steps approach: genome-wide screening, confirmation study on the quantified expression levels, and knock-down and transfection analyses of the candidates. The probable action pathways of selected genes were examined by Ingenuity Pathway Analysis using a large-scale database, The Cancer Genome Atlas. Results The first genome-wide screening study derived 16 highly correlative genes with cellular drug sensitivity in 15 cell lines (|R| > 0.8, P 0.5, P Conclusion We newly propose 4 molecules -AGR2, PDE4D,NINJ2 and CDC25B) as the powerful exploratory markers for prediction of cellular response to 3 key chemotherapeutic drugs in hypopharyngeal cancers and also suggest their potentials to be the therapeutic targets, which could contribute to the development of precision medicine of the essential chemotherapy in hypopharyngeal patients. (339 words).

Primordial odontogenic tumor (POT) is a newly classified, mixed epithelial and mesenchymal odontogenic tumor, with only 17 reported cases to date. Herein, we report a case of POT that occurred in the right maxilla of a 10-year-old boy and reveal unique features in comparison with those previously reported. Radiologically, the lesion presented as a well-defined, unilocular radiolucency with notable radiopaque foci on the periphery. Microscopically, the tumor was mainly composed of dental papilla-like myxoid fibrous connective tissue, largely surrounded by non-keratinized squamous epithelium with numerous calcified particles, and partly enclosed by inner enamel epithelium-like columnar cells and enamel organ-like structures accompanied with cuboidal and/or stellate reticulum-like cells. Immunohistochemically, the epithelium tested positive for cytokeratin 14 and 19. Moreover, amelogenin and ameloblastin, matrix proteins relating to enamel formation, were positive in the covering epithelium. The tumor was enucleated as a whole, and no recurrence was recorded thereafter. Although the presence of numerous calcified particles was unique, we diagnosed this lesion as POT based on the above-described features. Furthermore, we emphasize the importance of the differential diagnosis of POT and other odontogenic tumors that resemble corresponding tooth germ components.

Objective Regenerating loss of bone and nerve tissue is a serious concern among oral and maxillofacial surgeons, yet there is little information regarding the connection between bone metabolism and the nervous system. This study aimed to obtain evidence of this connection. Methods Osteocyte and Schwann cell lines were maintained in a non-contact co-culture system. Quantitative reverse-transcription polymerase chain reactions, immunoblot analyses, and cell proliferation assays were performed. The dendrite length of osteocytes was analyzed quantitatively. Results The dendrite length of osteocytes co-cultured with Schwann cells was significantly increased and associated with E11 protein expression. Schwann cell culture supernatant inhibited osteocyte proliferation and promoted dendrite elongation. However, myelin basic protein in Schwann cells was upregulated in the presence of osteocyte culture supernatant without changes in proliferation and dendrite extension. Schwann cells express the Sema3A gene and co-culture with osteocytes enhanced Sema3A mRNA expression. Conclusions Our data suggest that Schwann cells promote osteocyte maturation via humoral factors including Sema3A and osteocytes regulate myelination of Schwann cells.

Objective: Bone and nerve reconstruction is crucial for treating various diseases of the oral and maxillofacial region. However, the relationship between the bone and the nervous systems is not fully elucidated. Methods: Osteoblastic and sympathetic neuronal cell lines were maintained in contact co-culture. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR), immunoblot analysis, RNA interference, alkaline phosphatase (ALP) activity, and mineralization assays were performed. Results: Contact co-culture enhanced osteoblast calcification, promoted ALP activity, and increased the expression of Bglap and Runx2. Knockdown of Sema3A by RNA interference did not completely inhibit RUNX2 expression in contact co-culture. Sympathetic neuronal cells produce BMP-2; Bmp2 expression was upregulated in contact co-culture. Conclusions: We showed that sympathetic neuronal cells promote osteoblast differentiation by contact co-culture with osteoblasts, partly via SEMA3A. BMP-2 from sympathetic neuronal cells may promote osteoblast differentiation in a contact co-culture system.

Objective The aim of this study was to investigate postoperative horizontal relapse of the mandible in terms of the effects of the magnitude of mandibular setback movement and ramus inclination after LeFort I osteotomy and sagittal split ramus osteotomy. Study Design A retrospective study of patients who underwent orthognathic surgery for mandibular prognathism was performed. Postoperative relapse at point B was analyzed with regard to the magnitude of mandibular setback and the ramus inclination. Serial cephalograms were used to measure surgical changes and evaluate postoperative relapse. Results Nineteen men and 31 women (mean age 23.1 years) were retrospectively enrolled. Mean surgical backward movement of the mandible at point B was 8.2 mm, mean ramus inclination was 3.56 degrees, and mean relapse 1 year postoperatively was 0.95 mm (11.6%). Horizontal relapse of the mandible was significantly correlated with the magnitude of mandibular setback (r = –0.52; P = .007) and ramus inclination (r = 0.48; P = .014). Conclusions Increased horizontal mandibular relapse after bimaxillary surgery was associated with greater mandibular setback movement and increased proximal segment clockwise rotation. Mandibular relapse after bimaxillary surgery may be minimized via adequate control of intraoperative clockwise rotation of the proximal segment.

Giant cell arteritis (GCA) is a granulomatosis accompanied by angiitis that affects medium- and large-sized arteries. We present a case of GCA in a patient who presented with jaw claudication and occlusal pain. A 78-year-old man visited our department with left-sided facial pain associated with mastication. He also reported spontaneous left-sided facial pain and diminished vision. Based on his age, his new-onset left-sided headache, and a high erythrocyte sedimentation rate, he was diagnosed with GCA with immediate initiation of prednisolone (PSL) therapy. His fever subsided the following day. A temporal artery biopsy (TAB) was performed 7 days after hospitalization and showed a false-negative result. His left-sided facial pain and headache subsided 29 days after therapy initiation. He was diagnosed with bladder cancer 3 months later, and we considered a probable association between his left-sided facial pain and paraneoplastic syndrome. GCA was diagnosed clinically based on the American College of Rheumatology criteria. Prompt PSL treatment is warranted without waiting for TAB results to avoid visual loss or other complications in this patient population.

Chronic nonbacterial osteomyelitis is a rare bone disorder that can be found in the jaw. It is often associated with systemic conditions, including autoimmune deficiencies. However, little is known about how the genetic and immunologic background of patients influences the disease. Here, we focus on human leukocyte antigen (HLA), killer cell immunoglobulin-like receptors (KIRs), and their specific combinations that have been difficult to analyze owing to their high diversity. We employed a recently developed technology of simultaneous typing of HLA alleles and KIR haplotype and investigated alleles of the 35 HLA loci and KIR haplotypes composed of centromeric and telomeric motifs in 18 cases and 18 controls for discovery and 472 independent controls for validation. We identified an amino acid substitution of threonine at position 94 of HLA-C in combination with the telomeric KIR genotype of haplotype tA01/tB01 that had significantly higher frequency (>20%) in the case population than in both control populations. Multiple logistic regression analysis based on a dominant model with adjustments for age and sex revealed and validated its statistical significance and high predictive accuracy (C-statistic ≥0.85). Structure-based analysis revealed that the combination of the amino acid change in HLA-C and the telomeric genotype tA01/tB01 could be associated with lower stability of HLA-C. This is the first case-control study of a rare disease that employed the latest sequencing technology enabling simultaneous typing and investigated amino acid polymorphisms at HLA loci in combination with KIR haplotype.

To investigate morphologic and surgical risk factors causing neurosensory disturbances (NSDs) after bilateral sagittal split osteotomy (BSSO).A total of 237 patients (with 474 sides) who underwent BSSO were followed up for 1 year. Parameters examined included age, sex, asymmetry, mandibular movement direction, mandible cutting devices, split type, intraoperative exposure of the inferior alveolar nerve (IAN), contact between the IAN and screw, distance between mandibular canal and inner surface of the cortical bone (distance A), distance from lateral osteotomy to mental foramen (distance B), and NSD at 1 year postoperatively.NSD was observed in 62 (13.1%) sides of 51 patients. Exploratory factor analysis determined 4 factors (factor 1: distance A; factor 2: direction of mandibular movement; factor 3: distance B and cutting devices; factor 4: IAN exposure). Logistic regression analysis was performed using the above factors and age, sex, and asymmetry, making a total of 7 variables. Age, factor 1, and factor 4 were significant predictors of NSD.Advanced age, close distance between mandibular canal and inner surface of the cortical bone, and IAN intraoperative exposure are risk factors for NSD 1 year postoperatively. Cases at high risk for NSD must be treated with great care.

Background/Aim: Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a disease associated with a mouth opening limitation. Here, we conducted a bioinformatics analysis to examine gene expression patterns in patients with MMTAH in comparison to those with facial deformity (FD). Materials and Methods: Seven MMTAH patients and three FD patients were recruited. We conducted RNA sequencing analysis, quantitative reverse transcription polymerase chain reaction and immunoblot analysis. Results: Of the identified 19,767 mapped read tags that showed clear differential expression, 2,471 genes were significantly up-regulated and 2,849 genes were significantly down-regulated in patients with MMTAH compared to those in patients with FD. Among the up-regulated genes, ten genes were significantly increased. The distribution of up-regulated and down-regulated genes at different ages tended to be similar. Moreover, the protein levels of Ankyrin Repeat Domain 2, Troponin T1 and myosin heavy chain 7, which are associated with slow twitch fibers and mechanical loading, were strongly expressed in patients with MMTAH compared to those in patients with FD. Conclusion: The gene expression pattern in MMTAH patients was similar regardless of age. As the transition of fast-to-slow twitch in the skeletal muscle is induced by mechanical loading, and up-regulation of slow twitch molecules was observed in MMTAH patients, mechanical loading is suggested to be implicated in MMTAH.

Both Achilles and masticatory muscle tendons are large load-bearing structures, and excessive mechanical loading leads to hypertrophic changes in these tendons. In the maxillofacial region, hyperplasia of the masticatory muscle tendons and aponeurosis affect muscle extensibility resulting in limited mouth opening. Although gene expression profiles of Achilles and patellar tendons under mechanical strain are well investigated in rodents, the gene expression profile of the masticatory muscle tendons remains unexplored. Herein, we examined the gene expression pattern of masticatory muscle tendons and compared it with that of Achilles tendons under tensile strain conditions in the Japanese macaque Macaca fuscata. Primary tenocytes isolated from the masticatory muscle tendons (temporal tendon and masseter aponeurosis) and Achilles tendons were mechanically loaded using the tensile force and gene expression was analyzed using the next-generation sequencing. In tendons exposed to tensile strain, we identified 1076 differentially expressed genes with a false discovery rate (FDR) < 10−10. To identify genes that are differentially expressed in temporal tendon and masseter aponeurosis, an FDR of < 10−10 was used, whereas the FDR for Achilles tendons was set at > 0.05. Results showed that 147 genes are differentially expressed between temporal tendons and masseter aponeurosis, out of which, 125 human orthologs were identified using the Ensemble database. Eight of these orthologs were related to tendons and among them the expression of the glycoprotein nmb and sphingosine kinase 1 was increased in temporal tendons and masseter aponeurosis following exposure to tensile strain. Moreover, the expression of tubulin beta 3 class III, which promotes cell cycle progression, and septin 9, which promotes cytoskeletal rearrangements, were decreased in stretched Achilles tendon cells and their expression was increased in stretched masseter aponeurosis and temporal tendon cells. In conclusion, cyclic strain differentially affects gene expression in Achilles tendons and tendons of the masticatory muscles.

Introduction The central regulatory system that generates biological rhythms is regulated by circadian clock genes expressed by cells in the suprachiasmatic nucleus. Signals from this system are converted to adrenocortical hormones through the sympathetic nervous system and transmitted to peripheral organs. Another system releases glucocorticoids (GCs) in response to stress through the HPA-axis. Here we investigated the second messenger GC, which is shared by these systems and influences the expression of circadian clock genes of cells of the musculoskeletal system and in viable bone tissue. Methods We used mouse-derived cell lines, which differentiate into osteoblasts (MC3T3-E1, C2C12, and 10T1/2) as well as primary cultures of mouse osteoblasts to determine the expression levels of circadian clock genes that respond to GC. Mice (mPer2m/m) with an inactivating mutation in the period circadian clock 2 gene (Per2) exhibit marked dysrhythmia. Here we compared the bone morphologies of mPer2m/m mice with those of wild-type (WT) mice. Results The expression of major circadian clock genes was detected in each cell line, and their responsiveness to GC was confirmed. We focused on Per2, a negative regulator of the circadian clock and found that a Per2-loss-of-function mutation increased the proliferative capacity of osteoblasts. Treatment of mutant mice with slow-release GC and bisphosphonate affected the maturation of bone tissue, which reflects a tendency to retard calcification. Conclusion Our investigations of the mechanisms that regulate circadian rhythm function in tissues of the musculoskeletal system that respond to the stress hormone GC, reveal that Per2 is required for the maturation of bone tissue. Thus, the influences of the systems that control circadian rhythms and the responses to stress by regenerating tissue used for regenerative medicine must be considered and studied in greater detail., Highlights • Circadian clock genes expressed in musculoskeletal cells respond to GCs. • Per2, a negative regulatory gene, influences the proliferation of osteoblasts. • Circadian rhythms and GCs affect bone maturation and may control regenerating tissues.

Maxillary non-union is a rare complication that occurs after an orthognathic surgery such as Le Fort I osteotomy. Here, we report a case of refractory non-union after maxillary osteotomy, which required a second surgery with bone graft. A 33-year-old man who had undergone bimaxillary osteotomy complained of an abnormal sensation in the right alar part about 1 year after the surgery. The patient was diagnosed as having maxillary non-union. Although surgical stabilization was performed using titanium plates, the non-union remained. The re-fusion surgery was performed about 3 years after the bimaxillary osteotomy with autologous bone graft using a biodegradable fixation system. At the 1-year follow up, the maxillary non-union was healed both clinically and radiographically. Re-fusion surgery using bone graft with biodegradable fixation might be an effective treatment option in cases of prolonged non-union that becomes evident after a long period following the initial maxillary osteotomy.

There are cases in which patients complain of nasal obstruction after Le Fort I osteotomy, but the relationship with postoperative morphological changes in the nasal cavity, including the septum and inferior turbinate, is not clear.The authors evaluated the three-dimensional relationship of the morphological changes in the inferior turbinate before and after surgery in 84 patients who underwent Le Fort I osteotomy. Three classifications were made according to superior amount of maxillary movement at the base of nasal cavity.The high elevation group (4.0 mm or more) had 31 sides, the moderate elevation group had 93 sides, and the low elevation group (less than 2.0 mm) had 44 sides. The volume of inferior turbinate was 76.9 ± 12.8% of that before surgery in the high elevation group. The high- and moderate-elevation groups had significantly higher changes than the low elevation group, and the rate of contact between inferior turbinate and nasal cavity floor was 67.7%.After Le Fort I osteotomy, the volume of inferior turbinate tissue decreased in proportion to the amount of elevation of the maxilla. Although the soft tissue volume may be reduced due to adaptation of respiratory function, the inferior nasal passage was not completely ventilated in the high elevation group. If the elevation exceeds 4.0 mm counterclockwise with maxillary movement, it is necessary to consider the concomitant inferior turbinate resection because it may lead to nasal obstruction.

Background Although multilineage cells derived from oral tissue, especially the dental pulp, apical papilla, periodontal ligament, and oral mucosa, have neural crest-derived stem cell (NCSC)-like properties, the differences in the characteristics of these progenitor cell compartments remain unknown. The primary aim of the current study was to elucidate these differences. Methods Multilineage sphere-forming apical papilla-derived cells (APDCs), periodontal ligament-derived cells (PDLDCs), and oral mucosa stroma-derived cells (OMSDCs) from the same individuals were isolated from impacted developing teeth. All sphere-forming cells were characterized by biological analyses of stem cells. Additionally, composites of these cells and multiporous hydroxyapatite scaffolds were transplanted into immunocompromised mice. Results All sphere-forming cells expressed neural crest-related markers. Although APDCs and PDLDCs showed greater mineralized-cell differentiation, they exhibited poorer differentiation into adipocytes in vitro than OMSDCs. In immunocompromised mice, APDCs were better able to form hard tissues than PDLDCs and OMSDCs. Moreover, the expression of certain tissue-specific markers, such as CD24 and CD56 (NCAM1), differed among the tissue-derived cells. Surprisingly, the expression of only CD24 and CD56 could be discriminated among human tissues. Conclusions Our results suggest that although cells having NCSC-like properties present the same phenotype, they differ in the expression of certain markers and differentiation abilities. The present study is the first to demonstrate the differences in differentiation ability and molecular markers among multilineage human APDCs, PDLDCs, and OMSDCs obtained from the same patients and, concomitantly, the same sites and identify these tissue-specific markers in the human tooth developmental process.

Surface properties of biomaterials affect the morphologies and inflammatory responses of macrophages. Recently, biomaterial design utilizing these properties has been explored to build a scaffold for balancing the immune system in vivo. In the present study, polyrotaxane surfaces with different functional groups including methyl, amino, and sulfo groups are utilized to clarify the effect of molecular mobility and zeta potential of these surfaces on RAW264.7 macrophage responses. At 24 h post-seeding, the majority of the cells adhere onto each surface, and the initial spreading is suppressed by more negatively-charged polyrotaxane surfaces. From 24 to 48 h of incubation, the spreading areas on the unmodified and methylated surfaces significantly increase, whereas those on the aminated and sulfonated surfaces remain unchanged. These results suggest that the initially cellular spreading process depends on the zeta potential, while the subsequent spreading process is governed by the molecular mobility. After lipopolysaccharide stimulation, the less mobile surfaces induce higher expression of inflammation-related genes than highly mobile surfaces, suggesting that molecular mobility is the main factor modulating the inflammatory activity in macrophages. These findings indicate that the zeta potential and molecular mobility of polyrotaxane surfaces may play independent roles in the sequence of macrophage responses.

Introduction and importance Pediatric temporomandibular joint (TMJ) ankylosis can lead to significant difficulties in opening the mouth, as well as stunted mandibular growth resulting in a small mandible and facial asymmetry. For pediatric TMJ ankylosis, the ideal time to perform TMJ mobilization in order to achieve standard mandibular growth is unclear. Case presentation An 11-year-old boy with limited mouth opening was referred to our hospital. The patient had previously sustained a fracture of the left articular process of the mandible. Clinical examination revealed bony ankylosis of the left TMJ, and the condylar head was dislocated anteromedially. The bony ankylosis was removed at the age of 12 years. Mouth-opening exercises were started postoperatively. His mouth opening recovered without the development of severe facial asymmetry, and the dislocated condylar process served as a new joint and provided good jaw function until the most recent follow-up at the age of 21 years. Clinical discussion It is practical to perform surgical intervention after the child has achieved some growth and at a time when the surgery would not interfere with jaw development because the mouth opening can be improved by postoperative physical therapy. No interpositional implant was used because strict postoperative mouth opening exercises and the displaced condylar process, which was maintained to almost normal TMJ structure, were expected to preserve the gap between the ramus and the zygomatic arch. Conclusion Surgical intervention in the appropriate growth period is important to prevent the sequelae of mandibular growth suppression due to pediatric TMJ ankylosis., Highlights • We describe a case of pediatric temporomandibular joint ankylosis. • It can cause limited mouth opening, a small mandible, and facial asymmetry. • We observed good treatment outcomes and jaw function with a 9-year follow-up. • Mouth opening recovered without the development of severe facial asymmetry. • Arthroplasty in the appropriate growth period can prevent adverse effects.

Yes-associated protein (YAP), a transcriptional coactivator of the Hippo signaling pathway, has been widely implicated in vascular aging and diseases. For preventing vascular endothelial cell senescence, the design and development of biomaterials to regulate YAP activity are required. This study prepares polyrotaxane-coated surfaces with molecular mobility and clarifies the role of the mobility on vascular endothelial cell senescence through Hippo-YAP signaling. The polyrotaxane surface with high mobility induces cytoplasmic YAP localization in endothelial cells, whereas the surface with low mobility induces nuclear YAP localization. After serial cultivation of endothelial cells using polyrotaxane surfaces with different mobilities for 35 d, the endothelial cells aged on the polyrotaxane surface with high mobility exhibit higher proliferative potential, smaller spreading size, and lower activity of senescence-associated β-galactosidase than those aged on the surface with low mobility. These findings suggest that cellular senescence can be delayed by modulating the molecular mobility on polyrotaxane surfaces.

Objective Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a disease which exhibits limiting mouth opening caused by hyperplasia of the tendon and aponeurosis of bilateral masticatory muscles. Although it is unclear whether hyperplasticity of tendons in MMTAH is due to cyclic stretch, we hypothesize that cyclic stretch is the main cause of force on MMTAH. In this study, we examined decorin expression in the masticatory muscle tendon of MMTAH patients. We also examined decorin (Dcn) expression of tenocytes on which stretch forces are loaded to explore whether stretch forces affect yes-associated protein (YAP) signaling and whether Dcn expression is regulated by YAP. Methods Quantitative reverse-transcription polymerase chain reaction, immunoblot analysis and immunohistochemistry were performed in tendons of patients having MMTAH. Mechanical loading experiment for TT-D6 tendon fibroblastic cells using RNA interference technique was conducted. Results We found that Dcn expression is increased in tendons of MMTAH patients. We also showed that cyclic stretch force increases decorin expression in TT-D6 tendon fibroblastic cells and that Dcn expression is regulated via YAP in TT-D6 tendon fibroblastic cells acted upon by cyclic stretch. Conclusions Our results, for the first time, demonstrated that cyclic stretch induces decorin expression via YAP in tenocytes and Dcn is upregulated in tendons of MMTAH, suggesting that tendons of MMTAH were subjected to cyclic stretch conditions.

The aim of this in vivo study was to examine the degradation and biocompatibility of the WE43 magnesium alloy containing magnesium yttrium, rare earth elements, and zirconium over a one-year long-term follow-up period. Additionally, we compared anodized WE43 implants with monolithic ones and clarified the effect of the anodization. WE43 cylindrical implants with and without anodization (length, 10 mm; diameter, 0.3 mm) were transplanted into the rat tibia. In both groups, the development of corrosion and the change in implant volume were evaluated by in vivo micro-computed tomography until 12 months, and the bone tissue reaction was observed histologically. In the monolithic WE43 implants, hydrogen gas was evident until 14 days and the volume loss was 36.3% after 12 months. In the anodized WE43 implants, the development of hydrogen gas was inhibited and the volume loss was 27.7% after 12 months. The anodized WE43 implants showed a significantly slower corrosion process in the early phase. Therefore, these implants may require a prolonged period to degrade completely and may even resist complete degradation. At one year post surgery, bone maturation progressed and lamellar bone structure developed around the implant in both groups. In conclusion, the WE43 implants showed good long-term stability and biocompatibility in bone tissue.

Adipose-derived Mesenchymal stem cells have emerged as an attractive alternative source of cell therapy. While radiation therapy is an important application for head and neck cancer, the effect of adipose-derived mesenchymal stem cells on irradiated bone marrow-derived Mesenchymal stem cells is still unclear. Herein, we explored how clinical total radiation dose affect gene expression related with differentiation on murine bone marrow-derived mesenchymal stem cells and how murine adipose-derived mesenchymal stem cells affect irradiated murine bone marrow-derived mesenchymal stem cells. The clinical total radiation dose upregulates osterix mRNA expression. Moreover, adiposederived mesenchymal stem cells dramatically promoted the upregulation of osterix mRNA expression whereas inhibited NFATc1 mRNA expression. Taken as a whole, irradiated bone marrow-derived mesenchymal stem cells co-cultured with adipose-derived mesenchymal stem cells may exhibit osteogenic property.