Search

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.

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.

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.

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.

Hydrogels are promising materials in tissue engineering scaffolds for healing and regenerating damaged biological tissues. Previously, we developed supramolecular hydrogels using polyrotaxane (PRX), consisting of multiple cyclic molecules threaded by an axis polymer for modulating cellular responses. However, since hydrogels generally have a large amount of water, their adhesion to tissues is extremely weak. Herein, we designed a bilayered hydrogel with a PRX layer and a collagen layer (PRX/collagen hydrogel) to achieve rapid and strong adhesion to the target tissue. The PRX/collagen hydrogel was fabricated by polymerizing PRX crosslinkers in water with placement of a collagen sponge. The differences in components between the PRX and collagen layers were analyzed using Fourier transform infrared spectroscopy (FT-IR). After confirming that the fibroblasts adhered to both layers of the PRX/collagen hydrogels, the hydrogels were implanted subcutaneously in mice. The PRX hydrogel without collagen moved out of its placement site 24 h after implantation, whereas the bilayer hydrogel was perfectly adherent at the site. Together, these findings indicate that the bilayer structure generated using PRX and collagen may be a rational design for performing anisotropic adhesion.

The aim of this study is to report the differences in clinicopathological features of oral tongue squamous cell carcinoma (OTSCC) and survival between adolescent and young adult (AYA) patients and elderly patients and to find the prognosticators. The medical records of 101 AYA patients and 175 control patients with OTSCC who underwent surgery were reviewed. Variables related to prognosis and their clinicopathological associations were analyzed. The 5-year overall survival (5y-OS) rates of AYA and control patients with stage I and II OTSCC were 94.4% and 89.6% (P = .353), respectively, and their 5-year disease-free survival (5y-DFS) rates were 82.0% and 76.6%, respectively (P = .476). The 5y-OS rates of patients with stages III and IV OTSCC were 83.3% and 66.7% (P = .333), respectively, and their 5y-DFS rates were 75.0% and 57.1% (P = .335), respectively. Logistic regression analysis revealed that there was no significant clinicopathological difference in AYA and control group. Furthermore, there was no significant difference in 5y-OS rates between patients who underwent elective neck dissection (END) and those who underwent therapeutic neck dissection (TND) in both group (P = 0.717 and 0.688). Overall, the present study revealed the clinicopathological features and prognosis of OTSCC were similar in AYA patients and elderly patients. Moreover, as there was no significant difference in OS between patients who underwent END and those who underwent TND in AYA and control groups, our results suggest that the indication for END in AYA patients with clinical N0 OTSCC is similar to that for elderly patients.

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.

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.

Patients with masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) experience limited mouth opening due to restricted muscle extension. Hyperplastic aponeurosis and tendons lead to the restriction of muscle extension. The criteria for the diagnosis of MMTAH are limited mouth opening that progresses very slowly from adolescence, intraoral palpation reveals a hard cord-like structure along the overhang of the anterior border of the masseter muscle on maximum mouth opening, and a square mandible. Conservative treatment, including pharmacotherapy, occlusal splint and physical therapy are ineffective. The standard therapy is surgical treatment, such as anterior partial aponeurectomy of the masseter muscle and coronoidectomy. The long-term results are very satisfying.

The purpose of the current study was to compare the 1-year stability of skeletal after original Le Fort I osteotomy and maxillary step osteotomy. Fifty-two patients with prognathism underwent sagittal split ramus osteotomy with either original Le Fort I osteotomy or maxillary step osteotomy (26 patients each). Twelve cephalometric parameters were measured to evaluate postsurgical stability (lesser change was considered as enhanced stability) at 1 month (T1), 6 months (T2), and 1 year (T3) postoperatively. Only 3 parameters—vertical and horizontal distance of menton and vertical distance of point B—showed minimal but significant differences between the two groups. Lesser degrees of changes were observed after maxillary step osteotomy than after original Le Fort I osteotomy, and the differences were significant during the period between T1 and T2, but not from T1 to T3. Differences between the two groups were less in asymmetry cases required correction of the occlusal plane. In conclusion, differences between original Le Fort I osteotomy and maxillary step osteotomy were observed at the frontal points of the mandible; however, they were not clinically significant. It may be suggested that there is no significant difference in skeletal stability at 1 year after the two procedures.

Previous studies have revealed several genes involved in the carcinogenesis of oral cancer. However, the detailed mechanisms underlying this process are poorly understood. Previously, we established a database cataloging the transcriptional progression profile of oral carcinogenesis and identified several candidate genes with continuously increasing or decreasing expression, which specifically promote the transition of oral premalignant lesions to invasive carcinomas. In this study, using our microarray database, we attempted to determine significant genes that may contribute to metabolic alterations during oral carcinogenesis. After performing a literature survey, we focused on 15 candidate genes associated with glucose metabolism changes, particularly the tri-carboxylic acid cycle, and investigated the mRNA-expression status of these genes with our database. Only the solute carrier family 2 member 1 gene (also known as GLUT1), showed significantly increased mRNA expression during oral tumorigenesis. Immunohistochemical analysis confirmed that GLUT1 protein expression significantly increased during oral carcinogenesis. In addition, tumors with high expression of this protein significantly correlated with nodal status (P=0.002). Kaplan-Meier survival curves clearly demonstrated the adverse impact of high GLUT1 protein expression on disease-free survival (P=0.004). GLUT1 mRNA and protein expression increased in the order of normal mucosal tissues, epithelial dysplastic lesions and invasive carcinomas. Therefore, metabolic alterations, especially in glucose metabolism, occurred at the very early stage of development of oral malignancies. In addition, GLUT1 played a significant role in oral cancer, acquiring a malignant phenotype.

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.

Pyogenic granuloma (PG) is a granulomatous elevated lesion that occurs on the skin and mucous membranes. We herein report two cases of intra-oral PG that developed during the administration of ramucirumab for gastric cancer. Case 1 involved a 55-year-old man with a 6-mm tumor on the right tongue, and case 2 involved a 67-year-old man with a 5-mm tumor on the upper lip. The imbalance in angiogenesis caused by ramucirumab and the deterioration in the local oral environment were suggested to have caused the PG. Medical and dental collaboration is essential during the administration of ramucirumab.

To evaluate the stiffness of tongue squamous cell carcinoma (TSCC) using ultrasound strain elastography, a relatively new sonographic imaging technique, and to identify the factors that affect this stiffness. We treated 62 patients diagnosed with muscle invasive TSCC, who were treated at the department of oral surgery of our institution. Each patient’s tumor stiffness was semi-quantified according to the ratio of cancer to tongue muscle strain measured using ultrasound strain elastography (the strain ratio). Histopathological diagnosis was made on the same section as the ultrasound strain elastography. We set the following histopathological parameters: cancer cell content in the tumor area (%CCC), collagen fiber content in the tumor area (%CFC), and tumor-infiltrating inflammatory cell content in the stromal compartment (%TIIC). Spearman's rank correlation (rs) was used to assess correlations, and P values

Poly(ether ether ketone) (PEEK) is a high-performance thermoplastic used for several industrial applications due to its excellent mechanical properties. However, the use of PEEK is limited to dental materials because of its poor implant-bone integration. In the present study, methylated polyrotaxanes (MePRXs) with 4-vinylbenzyl groups, which are supermolecules composed of methylated α-cyclodextrins and poly(ethylene glycol) chains end-capped with 4-vinylbenzyl groups, were covalently tethered onto PEEK surfaces using photo-induced polymerization to improve their osteoblast compatibility. The surface-tethering of MePRXs onto PEEK surfaces was confirmed by analyzing their attenuated total reflectance Fourier transform infrared spectra and contact angles. When mouse preosteoblasts were cultured on the MePRX-PEEK and bare PEEK surfaces, the MePRX-PEEK surfaces showed significantly better proliferation and osteoblast differentiation than the bare PEEK surfaces. These results suggest that surface modification of PEEKs using MePRXs improves their osteoblast compatibility.

Polyrotaxanes are supramolecular assemblies consisting of cyclic molecules (e.g., α-cyclodextrins) and linear polymer chains (e.g., poly[ethylene glycol]), in which cyclic molecules can move along the polymer chain. Here, we examined the effect of functional groups introduced into the α-cyclodextrins of polyrotaxane on cell responses such as adhesion, proliferation, and differentiation. Polyrotaxane-based triblock copolymers modified with methyl (CH3, hydrophobic, and nonionic), hydroxy (OH, hydrophilic and nonionic), amino (NH2, cationic), and sulfo (SO3H, anionic) groups were coated on the surface of the culture plate to fabricate polyrotaxane surfaces with different surface chemistries. The chemical compositions of each surface were determined via time-of-flight secondary ion mass spectrometry and X-ray photoelectron spectroscopy. The contact angle hysteresis reflecting the molecular mobility and zeta potential of each polyrotaxane surface changed depending on the functional groups. When osteoblast and adipocyte differentiation was induced in human mesenchymal stem cells cultured on each polyrotaxane surface, the cells adhered to the SO3H-modified polyrotaxane surfaces exhibited osteoblast differentiation, whereas the cells adhered to the OH-, NH2-, and SO3H-modified polyrotaxane surfaces preferentially underwent adipocyte differentiation compared with those on the unmodified and CH3-modified polyrotaxane surfaces. Interestingly, the SO3H-modified polyrotaxane surfaces promoted both osteoblast and adipocyte differentiation. High molecular mobility and negative charge on the SO3H-modified polyrotaxane surfaces are expected to contribute to the facilitation of both osteoblast and adipocyte differentiation.

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common type of lymphatic tumor; however, extranodal DLBCLs that exhibit initial symptoms in the maxilla and mandible are rare. Moreover, DLBCL is clinically classified as a moderate to highly malignant lymphatic tumor that can progress rapidly; therefore, early diagnosis is crucial. However, diagnosis is difficult because the disease causes a diverse range of clinical symptoms with no characteristic imaging findings. We conducted a clinical investigation to clarify the clinical characteristics of DLBCL exhibiting initial manifestation in the maxilla and mandible.MethodsOf the 2748 patients with malignant tumors of the oral and maxillofacial region examined during a period of 11 years between January 2006 and December 2016 at our hospital, 27 primary cases diagnosed with DLBCL based on the chief complaint of symptoms in the gingiva and bone of the maxilla and mandible were enrolled. We evaluate on sex, age, whether treatment was provided by a previous physician, symptoms, disease period until seeking treatment, clinical diagnosis, laboratory findings, and imaging results.ResultsThere were 15 cases with maxilla involvement and 12 with mandible involvement. The median disease period until seeking of treatment was 60 d (3–450 d). All cases exhibited a tumor or a mass, and hypoesthesia of the chin was confirmed in 8 cases with mandible involvement. The clinical stage was stage I in 8 cases, stage II in 10 cases, and stage IV in 9 cases. Serum lactate dehydrogenase (LDH) levels were elevated in 13 of 22 patients. The overall survival rate was 63%.ConclusionThe possibility of Malignant Lymphomas (MLs), such as DLBCL, must be considered while treating lesions of the oral and maxillofacial region.

Oral tissue regeneration has received growing attention for improving the quality of life of patients. Regeneration of oral tissues such as alveolar bone and widely defected bone has been extensively investigated, including regenerative treatment of oral tissues using therapeutic cells and growth factors. Additionally, small-molecule drugs that promote bone formation have been identified and tested as new regenerative treatment. However, treatments need to progress to realize successful regeneration of oral functions. In this review, we describe recent progress in development of regenerative treatment of oral tissues. In particular, we focus on cyclodextrin (CD)-based pharmaceutics and polyelectrolyte complexation of growth factors to enhance their solubility, stability, and bioactivity. CDs can encapsulate hydrophobic small-molecule drugs into their cavities, resulting in inclusion complexes. The inclusion complexation of osteoinductive small-molecule drugs improves solubility of the drugs in aqueous solutions and increases in vitro osteogenic differentiation efficiency. Additionally, various anionic polymers such as heparin and its mimetic polymers have been developed to improve stability and bioactivity of growth factors. These polymers protect growth factors from deactivation and degradation by complex formation through electrostatic interaction, leading to potentiation of bone formation ability. These approaches using an inclusion complex and polyelectrolyte complexes have great potential in the regeneration of oral tissues.

Adenoid cystic carcinoma (AdCC) is a rare, indolent salivary gland tumor that is reported to be driven by fusion genes. However, MYB/MYBL1-NFIB fusions have been detected in60% of all AdCC cases and the oncogenic driver mutations in approximately 40% of AdCC remain unknown. Our aim was to identify novel gene fusions in AdCC.We investigated 20 AdCC cases using a targeted RNA sequencing panel to identify gene fusions and performed quantitative real-time reverse transcription polymerase chain reaction to assess MYB, MYBL1, and NFIB expression levels.A total of 36 fusion transcripts in 15 cases were detected and validated by Sanger sequencing. The MYB-NFIB and MYBL1-NFIB fusion genes were detected in 9 and 3 cases, respectively, in a mutually exclusive manner. Furthermore, novel gene fusions, namely, NFIB-EPB41L2, MAP7-NFIB, NFIB-MCMDC2, MYBL1-C8orf34, C8orf34-NFIB, and NFIB-CASC20, were identified. Among them, NFIB-EPB41L2 and NFIB-MCMDC2 are thought to activate MYB and MYBL1 expression, respectively, through the insertion of a genomic segment in proximity to MYB and MYBL1 genes, respectively.Six novel gene fusions other than MYB/MYBL1-NFIB were identified. The detection of novel fusion genes and investigation of the molecular mechanism will contribute to the development of novel molecular targeted therapies for this disease.

Summary Background Currently, sequential morphological changes of vascularized scapular bone for mandibular reconstruction have remained unreported. Methods We retrospectively analyzed 18 patients with defects on the lateral segment of the mandible who underwent postoperative computed tomography (CT) scanning at 1, 6, 12, and 24 months postoperatively. Using the cross-sectional coronal CT images during each assessment, we measured the height and thickness of the grafted scapular bone at points 10 and 30 mm away from the mesial segment and evaluated their differences over time. Then, the relationship between the morphological changes of the grafted scapular bone and the distance from the mesial bone segment, the number of occlusal supports on the contralateral side of the mandible, and the correlation of sex and age were evaluated. Results The height of the grafted scapular bone decreased by approximately 11% and its thickness increased by 14% within 24 months postoperatively. The bone thickness increase was greater at point 30 mm from the mesial bone segment. Patients with two occlusal contacts (premolar and molar) on the contralateral side had a significantly higher rate of bone thickness increase. Furthermore, the graft morphology was not associated with age or sex. Conclusion A vascularized scapular bone thickens over time, which depends on the distance from the mesial bone segment and the occlusal contact regions on the contralateral side of the mandible.

In the bilateral sagittal split osteotomy, a short lingual cut is made on the medial side of the ramus; however, in some cases, a true fracture occurs on the buccal side of the ramus. The purpose of this study was to evaluate the relationship between the splitting pattern of the mandible and the form of the mandible, the surgical technique used, and the postoperative occurrence of relapse after 'unfavorable' splits. The investigation examined 143 patients in whom a short lingual cut was attempted. The rate of unfavorable split was 14.7% (42/286). A strong correlation was observed between the reach of the lateral bone cut to the inferior border of the mandible and an unfavorable split. According to multivariate regression, the factors leading to an insufficient lateral bone cut were the degree of inward curvature of the ramus (P=0.001) and the position of the lateral bone cut (P=0.002). There was no significant difference in relapse between cases of unfavorable and normal splits. An unfavorable split does not affect the prognosis of the occlusion, but it is important to confirm the inward curvature of the ramus and set the position of the lateral bone cut adequately to avoid unfavorable splits.

Biointerfaces based on polyrotaxane (PRX), consisting of &alpha, cyclodextrins (&alpha, CDs) threaded on a poly(ethylene glycol) (PEG) chain, are promising functionalized platforms for culturing cells. PRXs are characterized by the molecular mobility of constituent molecules where the threading &alpha, CDs can move and rotate along the PEG chain. Taking advantage of this mobility, we have previously succeeded in demonstrating the regulation of cellular responses, such as cellular adhesion, proliferation, and differentiation. In the present study, we investigated differences in the cellular responses to PRX surfaces versus commercially available tissue culture polystyrene (TCPS) surfaces using fibroblasts, preosteoblasts, and preadipocytes. PRX surfaces were found to more significantly promote cellular proliferation than the TCPS surfaces, regardless of the cell type. To identify the signaling pathways involved in the activation of cellular proliferation, a DNA microarray analysis was performed. PRX surfaces showed a significant increase in the integrin-mediated cell adhesion and focal adhesion pathways. Furthermore, PRX surfaces also promoted osteoblast differentiation more than TCPS. These results suggest that structural features of PRX surfaces act as mechanical cues to dominate cellular proliferation and differentiation.

Fifty-four patients diagnosed with paresthesia on one side of the lower lip or skin in the chin area, were examined by multiple sensory tests and assessed self-reported subjective symptoms and the psychological state through questionnaires. Additionally, they were followed over time. Each sensory test threshold was evaluated and classified according to the individual way of scoring system, and the average sensory score (ASS) was used to analyze the correlation between self-reported symptoms and psychological state. On the second visit, all sensory test results had improved. The ASS was positively correlated with the pain questionnaire on the first visit; however, it did not correlate with psychological state or personality. There was a positive correlation between neuroticism and anxiety scores. The index of change (IC) of the ASS over time did not correlate with the IC of patients' self-reported symptoms or mental state. The IC of ASS data improved in all patients, but self-reported subjective symptoms did not show signs of improvement in all patients. When patients were divided into two groups according to age or sex, older females showed significantly more improvement than younger males on the psychological test.

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.

OBJECTIVE Masticatory muscle tendon-aponeurosis hyperplasia, which is associated with limited mouth opening, progresses very slowly from adolescence. The prevalence rates of this disease are higher among women than among men, suggesting oestrogen involvement. As parafunctional habits are frequently observed, mechanical stress is likely involved in the pathogenesis and advancement of this disease. To elucidate the pathological condition, we examined the effect of oestrogen on tenocyte function and the relationship between mechanical stress and crystallin beta A4 (Cryba4), using murine TT-D6 tenocytes. MATERIALS AND METHODS Cell proliferation assays, RT-PCR, real-time RT-PCR, Western blot analysis and mechanical loading experiments were performed. RESULTS The physiological dose of oestrogen increased the levels of scleraxis and tenomodulin in TT-D6 tenocytes. In contrast, forced expression of Cryba4 inhibited scleraxis expression in these cells. Surprisingly, oestrogen significantly promoted cell differentiation in the Cryba4-overexpressing TT-D6 tenocytes. Moreover, tensile force induced Cryba4 expression in these tendon cells. CONCLUSION Oestrogen and Cryba4 may be associated with the progression of masticatory muscle tendon-aponeurosis hyperplasia.

It is well known that osteonecrosis of the jaw is induced by the adverse effect of medication including bisphosphonates and anti-receptor activator of nuclear factor-kappa B ligand antibody. Recently, a few case reports showed that methotrexate is capable of inducing osteonecrosis of the jaw in the absence of antiresorptive or antiangiogenic agents. We herein introduce a case of osteonecrosis of the jaw with pancytopenia by low-dose methotrexate administration for rheumatoid arthritis. The patient of this case has been extracted teeth and subsequently suffered from the pain osteonecrosis of the jaw. Referring to our hospital, the patient was diagnosed as disseminated intravascular coagulation. Being received appropriate treatment, his condition was gradually recovered and he was discharged at thirty days after admission. We should bear this case in mind in examining patients being prescribed methotrexate.

This study re-examined the usefulness of surgery for the management of masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) through a comparison of the outcomes between patients who underwent surgery and those who did not. The duration of follow-up was 2 years. Twenty-eight patients who attended the study hospital and were given a diagnosis of MMTAH were included. Nineteen patients underwent surgery (surgical group) and nine patients were instructed to open their mouths wide once a day and did not undergo surgery (non-surgical group). Maximum mouth opening, impairment of daily activities, satisfaction, and the status of mouth opening training were evaluated after surgery. The mean increase in mouth opening after 2 years was 20.2mm in the surgical group and 2.4mm in the non-surgical group. Adequate mouth opening training led to satisfactory results 2 years postoperative, and sustained mouth opening training for 6 months after surgery was a key factor for obtaining good outcomes. The general condition and personality of individual patients should be evaluated carefully before surgery to estimate whether or not they can endure the pain associated with postoperative mouth opening training. The results of this study suggest that the surgical procedure is useful for the management of MMTAH.

Objective Peripheral blood-derived inflammation-based scores, such as the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and the combination of platelet count and NLR, have recently been proposed as prognostic markers in solid tumors. The purpose of this study was to investigate the validity of inflammatory markers as predictive prognostic factors for locally advanced oral squamous cell carcinoma (OSCC). In addition, we evaluated the potential correlation between systemic inflammation and local expression of COX2. Study Design Retrospective chart review and histologic analysis. Setting Tertiary referral academic center. Subjects and Methods We conducted a retrospective analysis of 94 patients with advanced OSCC treated with surgery at our hospital between 2007 and 2015. The relationship among patient survival, systemic inflammatory markers, and local COX2 expression was evaluated. Local COX2 expression in surgical specimens was measured by immunohistochemistry. Results High NLR and high PLR were associated with significantly shorter overall survival and cancer-specific survival. Multivariate analysis revealed that cN stage, NLR, and postoperative radiation/chemoradiation were significantly associated with overall survival and cancer-specific survival. PLR and combination of platelet count and NLR were significantly correlated with tumor expression of COX2. Finally, patients with cN2 stage disease and high local COX2 expression had a significantly worse prognosis than other patient groups. Conclusion Pretreatment inflammatory markers are useful as prognostic factors in advanced OSCC. Our study suggests that local COX2 may be affected by systemic inflammation and that the prognostic impact of COX2 expression depends on host factors and tumor characteristics.

Purpose In 2013, we reported the results of a third-generation oral moisture-checking device in a multicentre clinical study involving patients with dry mouth and healthy volunteers. Subsequently, several improvements have been made to the third-generation device, and a fourth-generation device is now commercially available. This study aimed to confirm the usefulness of this improved fourth-generation device in the diagnosis of dry mouth and to assess the physiological wetness of lingual mucosa by using this device. Materials and Method This multicentre study comprised subjects with dry mouth (dry mouth group) and those without dry mouth (healthy group). Results In this study, the degree of moisture was considerably different between the two groups. Receiver operating characteristic analysis revealed an area under the curve value of 0.831. Sensitivity and specificity values were close to 80% in cases where the degree of moisture ≥29.6 was defined as normal, ≤27.9 was defined as dry mouth, and 28.0–29.5 was defined as borderline dry mouth. Conclusions These results suggest that the improved fourth-generation moisture-checking device can be used for the diagnosis of oral dryness.

Objectives In patients with advanced oral squamous cell carcinoma (OSCC), surgical treatment is often administered in combination with radiotherapy-based postoperative adjuvant therapy. The aim of the present study was to determine the most appropriate dose by comparing patient outcomes between doses of 50- and 66-Gy for postoperative cervical irradiation. Materials and methods This retrospective study included patients who underwent postoperative cervical irradiation following neck dissection for OSCC with lymph nodes metastases, and their primary lesions were controlled. They were divided into the 50- and 66-Gy irradiation groups and were examined for sex, age, primary lesion site, tumor/node/metastasis stage, initial treatment for primary cancer, neck dissection procedure, number of metastatic lymph nodes, presence or absence of extranodal extension (ENE), concomitant anticancer agents, and therapeutic outcomes. Results A total of 78 patients met the clinical criteria for study enrollment. The 50- and 66-Gy postoperative cervical irradiation groups included 40 and 38 patients, with neck dissection performed at 45 and 38 sites, respectively. Cervical control rate was 97.5% and 97.3% in the 50- and 66-Gy irradiation groups (p = 0.74). The cumulative disease-specific 5-year survival rate was 85.6% and 88.3%, respectively, with no significant difference (p = 0.64). Conclusion The findings of our study indicate that the irradiation dose of 50 Gy is appropriate for postoperative cervical irradiation in patients with OSCC.

Background Splicing factor 3B subunit 4 (SF3B4) is a causative gene of an acrofacial dysostosis, Nager syndrome. Although in vitro analyses of SF3B4 have proposed multiple noncanonical functions unrelated to splicing, less information is available based on in vivo studies using model animals. Results We performed expression and functional analyses of Sf3b4 in mice. The mouse Sf3b4 transcripts were found from two-cell stage, and were ubiquitously present during embryogenesis with high expression levels in several tissues such as forming craniofacial bones and brain. In contrast, expression of a pseudogene-like sequence of mouse Sf3b4 (Sf3b4_ps) found by in silico survey was not detected up to embryonic day 10. We generated a Sf3b4 knockout mouse using CRISPR-Cas9 system. The homozygous mutant mouse of Sf3b4 was embryonic lethal. The heterozygous mutant of Sf3b4 mouse (Sf3b4+/- ) exhibited smaller body size compared to the wild-type from postnatal to adult period, as well as homeotic posteriorization of the vertebral morphology and flattened calvaria. The flattened calvaria appears to be attributable to mild microcephaly due to a lower cell proliferation rate in the forebrain. Conclusions Our study suggests that Sf3b4 controls anterior-posterior patterning of the axial skeleton and guarantees cell proliferation for forebrain development in mice.