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Abstract Neurofibromatosis type 1 (NF1) is an autosomal dominant nevus disease characterized by multiple manifestations, primarily café-au-lait macules and neurofibromas. Here, we present the case of an NF1 patient with 47,XYY mosaicism whose diagnosis was prompted by café-au-lait macules on the skin and mandibular neurofibromas. Targeted next-generation sequencing of the patient’s blood sample revealed a novel frameshift mutation in NF1 (NM_000267.3:c.6832dupA:p.Thr2278Asnfs*8) that is considered a pathogenic variant.

ABSTRACTImproving the damage tolerance and reliability of ceramic artificial bone materials, such as sintered bodies of hydroxyapatite (HAp), that remain in vivo for long periods of time is of utmost importance. However, the intrinsic brittleness and low damage tolerance of ceramics make this challenging. This paper reports the synthesis of highly damage tolerant calcium phosphate-based materials with a bioinspired design for novel artificial bones. The heat treatment of isophthalate ion-containing octacalcium phosphate compacts in a nitrogen atmosphere at 1000°C for 24 h produced an HAp/β-tricalcium phosphate/pyrolytic carbon composite with a brick-and-mortar structure (similar to that of the nacreous layer). This composite exhibited excellent damage tolerance, with no brittle fracture upon nailing, likely attributable to the specific mechanical properties derived from its unique microstructure. Its maximum bending stress, maximum bending strain, Young’s modulus, and Vickers hardness were 11.7 MPa, 2.8 × 10‒2, 5.3 GPa, and 11.7 kgf/mm2, respectively. The material exhibited a lower Young’s modulus and higher fracture strain than that of HAp-sintered bodies and sintered-body samples prepared from pure octacalcium phosphate compacts. Additionally, the apatite-forming ability of the obtained material was confirmed in vitro, using a simulated body fluid. The proposed bioinspired material design could enable the fabrication of highly damage tolerant artificial bones that remain in vivo for long durations of time.

Abstract 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

Abstract Background Diffuse 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 as 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 that exhibits initial manifestation in the maxilla and mandible. Methods Of the 2748 patients with malignant tumors of the oral and maxillofacial region examined at our hospital during a period of 11 years between January 2006 and December 2016, 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 in this study. Evaluations were based on sex, age, whether treatment was provided by a previous physician, symptoms, duration of disease until treatment was sought, clinical diagnosis, laboratory findings, and imaging results. Results There were 15 cases that involved the maxilla and 12 that involved the mandible. The median duration of disease until treatment was sought was 60 d (3–450 d). All cases exhibited a tumor or a mass, and hypoesthesia of the chin was confirmed in eight cases wherein the mandible was involved. The clinical stages were stage I in eight cases, stage II in ten cases, and stage IV in nine cases. Serum lactate dehydrogenase (LDH) levels were elevated in 13 of 22 patients. The overall survival rate was 63%. Conclusions Symptoms associated with nontender swelling and numbness of the lip or chin in the absence of other findings such as dental infections should raise suspicions about DLBCL. Patients should be provided appropriate imaging and accurate biopsy assessments to improve prognosis.

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.

Summary: Total joint replacement (TJR) of the temporomandibular joint (TMJ) is a promising surgical procedure and device for treating end-stage diseases of the TMJ. For the functional and aesthetic reconstruction of the oral and maxillofacial head and neck region, TMJ TJR significantly helps maintain the patient’s quality of life in terms of a better diet, mastication, speech and social interaction. TMJ TJR was approved by regulatory authorities in 2019 in Japan, thus enabling the clinical application of the TJR system. However, the surgery demands particularly difficult and high-risk procedures, necessitating the prudent selection of indicated patients. The joint committee of the Japanese Society of Oral and Maxillofacial Surgeons and Japanese Society for Temporomandibular Joint is working together to develop an appropriate clinical guideline for TMJ TJR.

The transcription factor tumour protein 63, encoded by the TP63 gene, is a regulator of epidermal development. Heterozygous mutations in TP63 cause a variety of human ectodermal dysplasia disorders, including ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome, split hand/foot malformation 4, Rapp-Hodgkin syndrome, limb mammary syndrome, and acro-dermato-ungual-lacrimal-tooth syndrome. There are genotype-phenotype correlations in some of these syndromes, and the number of cases with overlapping symptoms has been increasing. The phenotypic spectrum and expressivity of TP63 mutation-associated syndromes complicate its clinical diagnosis and classification. Here, we present an updated review of TP63 mutation mapping information, together with a comprehensive overview of TP63 mutation-associated syndromes. We show that several cases with the same mutation have been previously diagnosed with different syndromes. This study will be useful for the diagnosis and classification of TP63 mutation-associated syndromes.

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. Keywords: Circadian rhythm, Glucocorticoids, Period circadian clock 2 gene, Second messenger

Calcium pyrophosphate dihydrate (CPPD) deposition disease is a benign disorder characterized by acute gouty arthritis-like attacks and first reported by McCarty. CPPD deposition disease rarely occurs in the temporomandibular joint (TMJ), and although confirmation of positive birefringence by polarized light microscopy is important for diagnosis, it is not reliable because other crystals also show birefringence. We reported a case of CPPD deposition disease of the TMJ that was diagnosed by chemical analysis. A 47-year-old man with a chief complaint of persistent pain in the right TMJ and trismus was referred to our department in 2020. Radiographic examination revealed destruction of the head of the mandibular condyle and cranial base with a neoplastic lesion involving calcification tissue. We suspected CPPD deposition disease and performed enucleation of the white, chalky masses. Histopathologically, we confirmed crystal deposition with weak birefringence. SEM/EDS revealed that the light emitting parts of Ca and P corresponded with the bright part of the SEM image. Through X-ray diffraction, almost all peaks were confirmed to be CPPD-derived. Inductively coupled plasma atomic emission spectroscopy revealed a Ca/P ratio of nearly 1. These chemical analyses further support the histological diagnosis of CPPD deposition disease.

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.

Recently, an increasing number of reports have described squamous cell carcinomas arising in free flaps used for maxillofacial reconstruction. Here, we report the case of a patient with second primary carcinoma arising in a free flap, and present a literature review of possible risk factors. A 59-year-old woman was referred to our department complaining of swelling in the lower gingiva in 2012. Her previous history included hypopharyngeal carcinoma for which she had undergone surgery and high-dose radiation therapy. We diagnosed her with osteoradionecrosis, and she underwent mandibular resection and simultaneous reconstruction with an anterolateral thigh flap. In 2016, the patient presented with an exophytic swelling with leucoderma on the free flap. We diagnosed the lesion as a second primary squamous cell carcinoma derived from the free flap used for the reconstruction. She underwent resection of the free flap under general anesthesia. Interestingly, we found mucosalization and hyphae-like Candida on the histopathological examination. Regarding factors of cancerization, it is reasonable to consider causes that lead to chronic inflammation, such as mucosalization (alteration in the environment), external stimuli in the oropharyngeal area, or candidasis. Keywords: Squamous cell carcinoma, Second primary carcinoma, Oral cavity, Free flap, Mucosalization, Candida

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.

This paper reports data on the bone, specifically the tibia and mandible, of nonobese diabetic mice with severe combined immunodeficiency disease (NOD–SCID mice) treated with zoledronic acid (ZA) and prednisolone (PSL). The data described here are related to the research article titled “Zoledronic acid basically increases circulating soluble RANKL level in mice, and in glucocorticoid-administrated mice, more increases lymphocytes derived sRANKL by bacterial endotoxic stimuli” [1]. The present data and the NOD–SCID mice experiments described contain insights into the role of bone-remodeling factors induced by ZA treatment. Keywords: Zoledronic acid, NOD–SCID mice, Medication-related osteonecrosis of the jaw

Limited mouth opening is a common health problem that interferes with eating, makes examination of the oral cavity difficult, and may increase the mortality rate during emergency intubation. Here we introduce a disease designated as masticatory muscle tendon-aponeurosis hyperplasia, which is a new clinical condition of limited mouth opening. Most oral surgeons and dentists are still unaware of this disease condition, thus increasing the risk of incorrect diagnosis as some other disease, such as temporomandibular joint disorder. We will review the clinical features, epidemiology, pathophysiology, etiology, diagnosis, treatment, and prognosis of this disease and also appraise the literature available on the subject.

Background/purpose: Adrenocorticotropic hormone (ACTH) plays a vital role in maintaining the function of the hypothalamic–pituitary–adrenal axis. Recent studies have demonstrated that ACTH directly affects the proliferation and differentiation of bone cells. However, the ACTH concentrations used in these studies appear to be markedly higher than the physiological concentrations. Here, we investigated whether ACTH at pathophysiological concentration affects the proliferation and differentiation of osteoblasts and osteoclasts. Materials and methods: We evaluated the effect of ACTH at pathophysiological concentration on osteoclasts using tartrate-resistant acid phosphatase staining and on osteoblasts using alkaline phosphatase activity assay. Additionally, we conducted reverse transcriptase-polymerase chain reaction analysis. Results: We found that at pathophysiological concentration, ACTH does not affect osteoblast proliferation and inhibits osteoblast differentiation. Moreover, we showed that at pathophysiological concentration, ACTH does not affect the proliferation of bone marrow macrophages, but promotes differentiation of osteoclasts and induces expression of genes involved in bone resorption. Conclusion: Taken together, our findings suggest that ACTH modulates the proliferation and differentiation of bone cells in vitro at pathophysiological concentration.

Biointerfaces based on polyrotaxane (PRX), consisting of α-cyclodextrins (α-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 α-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.

Background. Acquired hemophilia A (AHA) is a rare disorder which results from the presence of autoantibodies against blood coagulation factor VIII. The initial diagnosis is based on the detection of an isolated prolongation of the activated partial thromboplastin time (aPTT) with negative personal and family history of bleeding disorder. Definitive diagnosis is the identification of reduced FVIII levels with evidence of FVIII neutralizing activity. Case report. We report a case of a 93-year-old female who was diagnosed as AHA after tooth extraction at her home clinic. Prolongation of aPTT and a reduction in factor VIII activity levels were observed with the presence of factor VIII inhibitor. AHA condition is mild. However, acute subdural hematoma of this patient occurred due to an unexpected accident in our hospital. Hematoma was gradually increased and the patient died 13 days after admission. Discussion. Although AHA is mild, intracranial bleeding is a life-threatening condition. We also should pay attention to the presence of AHA patients when we extract teeth.

Introduction: Recurrent aphthous stomatitis and oral lichen planus are local chronic inflammatory diseases which are implicated in T cell-mediated immunity. According to the systematic review, there is insufficient evidence to support any specific treatment for T-cell mediated oral diseases. The hypothesis: In this paper, we propose a hypothesis that recurrent aphthous stomatitis and oral lichen planus can be treated with selective α7 subunit of nicotinic acetylcholine receptor (α7 -nAChR) agonists. Our hypothesis is supported by the following two facts. First, the pathophysiological conditions, T h 1/T h 17 cell activation and autonomic nervous system dysfunction, are observed in T-cell mediated oral diseases as well as in T-cell mediated systemic diseases such as rheumatoid arthritis. Second, the cholinergic anti-inflammatory pathway is inhibited in systemic T-cell mediated chronic inflammatory diseases. On the other hand, treatment with α7 -nAChR agonists which activate the cholinergic anti-inflammatory pathway suppresses neuroinflammation via inhibition of T h 1/T h 17 responses in animal model of systemic T-cell mediated chronic inflammatory diseases. We thus expect that selective α7 -nAChR agonists will be effective for the treatment of T-cell mediated oral diseases. Evaluation of the hypothesis: To test our hypothesis, we need to develop in vivo mouse model of T-cell mediated oral diseases. To evaluate the therapeutic effect of a selective α7 -nAChR agonist, we choose ABT-107 because of its safety and tolerability. We believe that the selective α7 -nAChR agonist, especially ABT-107, may be a therapeutic drug to treat T-cell mediated oral diseases.

Bone morphogenetic protein 2 (BMP-2) has received considerable attention because of its osteoinductivity, but its use is limited owing to its instability and adverse effects. To reduce the dose of BMP-2, complexation with heparin is a promising approach, because heparin enhances the osteoinductivity of BMP-2. However, the clinical use of heparin is restricted because of its anticoagulant activity. Herein, to explore alternative polymers that show heparin-like activity, four polycarboxylates, poly(acrylic acid) (PAA), poly(methacrylic acid) (PMAA), poly(aspartic acid) (PAsp), and poly(glutamic acid) (PGlu), were selected and their capability to modulate the osteoinductivity of BMP-2 was evaluated. Dynamic light scattering indicated that these polycarboxylates formed polyelectrolyte complexes with BMP-2. The osteogenic differentiation efficiency of MC3T3-E1 cells treated with the polycarboxylate/BMP-2 complexes was investigated in comparison to that of the heparin/BMP-2 complex. As a result, PGlu/BMP-2 complex showed the highest activity of alkaline phosphatase, which is an early-stage marker of osteogenic differentiation, and rapid mineralization. Based on these observations, PGlu could serve as an alternative to heparin in the regenerative therapy of bone using BMP-2.

Objective: Donepezil, an inhibitor of acetylcholinesterase (AChE) targeting the brain, is a common medication for Alzheimer's disease. Interestingly, a recent clinical study found that administration of this agent is associated with lower risk of hip fracture independently of falling, suggesting its direct effect on bone tissues as well. AChE has been reported to be involved in osteoblast function, but the role of AChE on osteoclastogenesis still remains unclear. We analyzed the effect of AChE and donepezil on osteoclastogenesis in vivo and in vitro. Methods: Cell-based assays were conducted using osteoclasts generated in cultures of murine bone marrow macrophages (BMMs) with receptor activator of nuclear factor-kappa B ligand (RANKL). The effect of donepezil was also determined in vivo using a mouse model of RANKL-induced bone loss. Results: Recombinant AChE in BMMs cultured with RANKL further promoted RANKL-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast differentiation. RANKL also upregulated AChE expression in BMMs. RNA interference-mediated knockdown of AChE significantly inhibited RANKL-induced osteoclast differentiation and suppressed gene expression specific for osteoclasts. AChE upregulated expression of RANK, the receptor of RANKL, in BMMs. Donepezil decreased cathepsin K expression in BMMs and the resorptive function of osteoclasts on dentine slices. Donepezil decreased RANK expression in BMMs, resulting in the inhibition of osteoclast differentiation with downregulation of c-Fos and upregulation of Id2. Moreover, administration of donepezil prevented RANKL-induced bone loss in vivo, which was associated with the inhibition of bone resorption by osteoclasts. Conclusions: AChE promotes osteoclast differentiation in vitro. Donepezil inhibits osteoclast function in vitro and prevents bone loss by suppressing bone resorption in vivo, suggesting the possibility that donepezil reduces fracture risk in patients with Alzheimer's disease.

Background. Essential palatal tremor is a disorder of unknown etiology involving involuntary movement of the uvula and soft palate. Treatment attempts including drugs or surgery have been conducted to cease the rhythmical movement. Case Report. A 55-year-old female visited our department complaining of a sudden, noticeable, intermittent, and rhythmical clicking noise in her throat for five years. Oral examination revealed rhythmical contractions of the soft palate with clicking at the frequency of 120 per min. Magnetic resonance imaging (MRI) examination of the brain performed after consulting with the department of neuropathic internal medicine showed no abnormalities. Thus, essential palatal tremor was diagnosed. The symptoms improved with cognitive behavioral therapy without drugs or surgical treatments. The patient is now able to stop the rhythmical movement voluntarily. Discussion. Cognitive behavioral therapy might be suitable as first-line therapy for essential palatal tremor because the therapy is noninvasive.

The special sense of taste guides and guards food intake and is essential for body maintenance. Salty and sour tastes are sensed via ion channels or gated ion channels while G protein-coupled receptors (GPCRs) of the taste receptor type 1 (T1R) family sense sweet and umami tastes and GPCRs of the taste receptor type 2 (T2R) family sense bitter tastes. T1R and T2R receptors share similar downstream signaling pathways that result in the stimulation of phospholipase-C-β2. The T1R family includes three members that form heterodimeric complexes to recognize either amino acids or sweet molecules such as glucose. Although these functions were originally described in gustatory tissue, T1R family members are expressed in numerous non-gustatory tissues and are now viewed as nutrient sensors that play important roles in monitoring global glucose and amino acid status. Here, we highlight emerging evidence detailing the function of T1R family members in the musculoskeletal system and review these findings in the context of the musculoskeletal diseases sarcopenia and osteoporosis, which are major public health problems among the elderly that affect locomotion, activities of daily living, and quality of life. These studies raise the possibility that T1R family member function may be modulated for therapeutic benefit.

Background/Aim: Masticatory muscle tendonaponeurosis 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 upregulated 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of non-receptor tyrosine kinases (NRTKs) in inflammation-induced osteoclastogenesis. Methods: Microarray analyses of global mRNA expression during receptor activator of NF-jB ligand (RANKL) and RANKL plus tumor necrosis factor (TNF)-a-induced osteoclast differentiation were performed. The inhibitory effect on TNF-a-induced osteoclast differentiation of A-419259, a potent inhibitor of hematopoietic cell kinase (Hck), was examined. The in vivo therapeutic effect of A-419259 treatment on lipopolysaccharide (LPS)-induced inflammatory bone destruction was evaluated. Results: We confirmed that Hck expression was selectively increased among the NRTKs during the osteoclast differentiation induced by RANKL and TNF-a, but not by RANKL alone. RANKL and TNF-a-induced osteoclast differentiation and they were dose-dependently inhibited by A-419259 treatment through inhibition of the expression of key regulators of osteoclastogenesis, including Prdm1 and Nfatc1. Notably, LPS-induced inflammatory bone loss in murine calvarial bones was ameliorated by the administration of A-419259. Conclusions: Our results demonstrate that the administration of A-419259 is effective for the inhibition of osteoclast differentiation induced by TNF-a in the presence of RANKL. Therefore, an inhibitor of Hck may be useful as a potent anti-osteoclastogenic agent for the treatment of inflammatory bone destruction. [ABSTRACT FROM AUTHOR]

A 28-year-old man visited our hospital with the chief complaint of trismus. Computed tomography revealed a well-defined, soft tissue tumor, 66 × 45 × 21 mm, with a distinct boundary in the inner region of the zygomatic arch. The mass contained various sizes of bone-like hard tissue, some of which adhered to the right coronoid process. A contrast-enhanced magnetic resonance image showed that the mass was composed mainly of adipose tissue. Tumorectomy was performed, and the histopathological diagnosis was osteolipoma. At 2-year follow-up, mouth opening had increased from 31 mm to 50 mm. (J Oral Sci 58, 141-144, 2016). [ABSTRACT FROM AUTHOR]

Objective: This retrospective study was conducted to reveal usability of surgical treatment in the cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) stage 2 with sequestrum. Patients and Methods: Study subjects included 18 patients having BRONJ stage 2 with sequestrum and 12 non-BRONJ patients with nearly equal clinical states of BRONJ stage 2. Patient characteristics, frequency of inciting factors of osteonecrosis, and treatment results were compared between BRONJ group and non-BRONJ groups. In addition, correlation between treatment methods (conservative therapy, sequestrum curettage, and sequestrectomy) and treatment results and correlation between the administration route of bisphosphonates (BPs) (oral or intravenous) and treatment results were examined statistically. The Student's t-test and Fisher's exact test were performed for statistical analysis. Results: Patient characteristics, frequency of inciting factors of osteonecrosis, and treatment results showed no significant differences between the two groups. In the BRONJ group, treatment result of sequestrectomy was significantly better than conservative therapy/sequestrum curettage (P < 0.001), however, no significant difference was observed in the non-BRONJ group. No significant difference was found in correlation between the administration route of BPs and treatment results in the BRONJ group. Conclusion: Treatment outcome of sequestrectomy was better than conservative therapy/sequestrum curettage in BRONJ stage 2 cases with sequestrum. [ABSTRACT FROM AUTHOR]

Most clinicians throughout the world are probably unaware of the existence of masticatory muscle tendon-aponeurosis hyperplasia (MMTAH), potentially leading to misdiagnoses such as temporomandibular joint disorder (TMD). Here, we introduce this disease from the viewpoint of education. In February 2013, a 39-year-old woman presented with limited mouth opening. Her facial configuration was characterized by a square mandible. There was no evidence of TMD. Magnetic resonance imaging (MRI) showed bilateral enlargement of the masseter muscles. Additionally, a 'thick' aponeurosis of the anterior aspect of the masseter muscle was noted bilaterally. On maximal mouth opening, intraoral palpation along the anterior border of the masseter muscle confirmed a hard cord-like structure, consistent with the findings on MRI. MMTAH was diagnosed. When clinicians notice limited mouth opening on oral examination, they should be knowledgeable about diseases associated with limited mouth opening and a square mandibular configuration, such as MMTAH. [ABSTRACT FROM AUTHOR]

Satellite cells are skeletal muscle stem cells that provide myonuclei for postnatal muscle growth, maintenance, and repair/regeneration in adults. Normally, satellite cells are mitotically quiescent, but they are activated in response to muscle injury, in which case they proliferate extensively and exhibit up-regulated expression of the transcription factor MyoD, a master regulator of myogenesis. MyoD forms a heterodimer with E proteins through their basic helix-loop-helix domain, binds to E boxes in the genome and thereby activates transcription at muscle-specific promoters. The central role of MyoD in muscle differentiation has increased interest in finding potential MyoD regulators. Here we identified transducin-like enhancer of split (TLE3), one of the Groucho/TLE family members, as a regulator of MyoD function during myogenesis. TLE3 was expressed in activated and proliferative satellite cells in which increased TLE3 levels suppressed myogenic differentiation, and, conversely, reduced TLE3 levels promoted myogenesis with a concomitant increase in proliferation. We found that, via its glutamine- and serine/proline-rich domains, TLE3 interferes with MyoD function by disrupting the association between the basic helix-loop-helix domain of MyoD and E proteins. Our findings indicate that TLE3 participates in skeletal muscle homeostasis by dampening satellite cell differentiation via repression of MyoD transcriptional activity. [ABSTRACT FROM AUTHOR]

Osteoclast formation is regulated by balancing between the receptor activator of nuclear factor-κB ligand (RANKL) expressed in osteoblasts and extracellular negative regulatory cytokines such as interferon-γ (IFN-γ) and interferon-β (IFN-β), which can suppress excessive bone destruction. However, relatively little is known about intrinsic negative regulatory factors in RANKL-mediated osteoclast differentiation. Here, we show the paired-box homeodomain transcription factor Pax6 acts as a negative regulator of RANKL-mediated osteoclast differentiation. Electrophoretic mobility shift and reporter assays found that Pax6 binds endogenously to the proximal region of the tartrate acid phosphatase (TRAP) gene promoter and suppresses nuclear factor of activated T cells c1 (NFATc1)-induced TRAP gene expression. Introduction of Pax6 retrovirally into bone marrow macrophages attenuates RANKL-induced osteoclast formation. Moreover, we found that the Groucho family member co-repressor Grg6 contributes to Pax6-mediated suppression of the TRAP gene expression induced by NFATc1. These results suggest that Pax6 interferes with RANKL-mediated osteoclast differentiation together with Grg6. Our results demonstrate that the Pax6 pathway constitutes a new aspect of the negative regulatory circuit of RANKL-RANK signaling in osteoclastogenesis and that the augmentation of Pax6 might therefore represent a novel target to block pathological bone resorption. [ABSTRACT FROM AUTHOR]