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Background: Cases of facial asymmetry with chin deviation and canted occlusal plane represent a challenge in orthodontic treatment. Case Report: We report successful surgical orthodontic treatment for skeletal Class I with severe facial asymmetry. Miniscrew anchorage was used to decompensate the canted occlusal plane in presurgical orthodontic treatment with a fixed appliance by the intrusion of the maxillary right molars and extrusion of the left molars. Then, orthognathic surgery consisting of bilateral sagittal split osteotomy for asymmetric mandibular setback was performed. Treatment resulted in marked improvement of facial asymmetry. Conclusion: The use of miniscrew implant anchorage may represent a superior presurgical orthodontic treatment and expand the possibility of treatment by one-jaw surgery.

Skeletal fractures are most common large-organ traumatic injuries that impact the functions and esthetic outcomes and quality of life. Unfortunately, infection during the fracture healing process and inadequate blood supply to the bone impede reduced ability to produce cartilage and effective bone callus formation, leading to nonunion or delayed union fracture. Therefore, studying the mechanism of fracture healing is an important task in solving the problem of fracture healing failure. Animal models of bone fracture healing are important tools to investigate the pathogenesis and develop treatment strategies. This protocol introduces researchers to a bone repair model utilizing the ribs of rats and the immunohistological expression of cellular communication network factor/connective tissue growth factor (CTGF/CCN2) during the fracture healing processes.

Bone metastasis and bone destruction are common occurrences in human malignancies, including breast, prostate, and lung cancer, and are associated with a high morbidity rate because of intractable bone pain, pathological fractures, hypercalcemia, and nerve compression. Animal models of bone metastasis and bone destruction are important tools to investigate the pathogenesis and develop treatment strategies. However, there are few models of spontaneous bone metastasis despite the fact that animals often spontaneously develop cancer. Here, we describe methods for developing a mouse model of breast cancer bone metastasis achieved by injection of MDA-MB-231 breast cancer cells into the left cardiac ventricle. In addition, we introduce mouse model of the bone destruction by injection of SAS oral squamous cell carcinoma cells into the bone marrow space of the right tibial metaphysis. These assays can be applied to studies on roles of cellular communication network factor/connective tissue growth factor (CTGF/CCN2) protein in tumor metastasis and development of treatment strategies targeting CCN proteins.

Angiogenesis, the process of generating new blood vessels from an existing vasculature, is essential in normal developmental processes such as endochondral ossification and in numerous kinds of pathogenesis including tumor growth. A part from the actin of angiogenic factor or antiangiogenic factor, it is still unknown at which stage of the angiogenic cascade these agents affect angiogenesis. Here, we describe methods for the use of cellular communication network factor/connective tissue growth factor (CTGF/CCN2) and CCN2-neutralizing antibody in the currently used principal angiogenesis assays, including those in vitro ones for the proliferation, migration, adhesion, and tube formation of endothelial cells and in vivo assays such as those utilizing type I collagen implantation and the chick chorioallantoic membrane (CAM). In addition, we introduce an autofluorescence imaging of blood vessels in the subcutaneous tumor xenograft mouse model. These assays can be applied to studies on roles of CCN proteins in tumor metastasis and development of treatment strategies targeting CCN proteins.

Highlights • MMTAH is a new clinical entity, misdiagnosed as temporomandibular joint disorder. • MMTAH is diagnosed based on a square mandible, cord-like masseter muscle aponeurosis, and limited mouth-opening. • Aponeurectomy combined with coronoidectomy is the treatment of choice for a better prognosis. • It is important to evaluate the patient’s compliance with mouth-opening training before surgery., Introduction Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a new clinical entity that presents mainly with trismus due to hyperplasia of the masseter aponeurosis and temporalis muscle tendon. However, the etiological factors of this disease are unknown; it is often mistreated as temporomandibular joint disorder (TMD). Presentation of case We report a 32-year-old female patient complaining of bilateral pain in her jaw and difficulty opening her mouth. She was first diagnosed as TMD and treated with a splint; however, her symptoms did not improve. Clinical examination revealed a square mandible, tenderness in the left and right temporalis muscles and masseter muscles, and tenderness along the anterior border of the masseter muscle. Her maximum mouth-opening was 30 mm. Short TI inversion recovery magnetic resonance imaging showed areas of low intensity at the anterior border of the masseter muscle and around the coronoid process where the temporalis muscle tendon attaches. Consequently, the diagnosis made based on the clinical and radiographic findings was MMTAH. Bilateral coronoidectomy was performed, followed by a rehabilitation program for six months. The maximum opening was maintained at 48 mm two years after the operation. Discussion MMTAH was treated as type 1 TMD until it was recognized as a new disease at the conference for the Japanese Society for Oral and Maxillofacial Surgeons. Since then, many clinicians have become aware of this particular condition, and different treatment modalities have been proposed. Conclusion Clinicians should consider MMTAH as a differential diagnosis when the patient’s chief complaint is gradually decreasing mouth-opening.

We reported an extremely rare case regarding intraosseous clear cell variant of mucoepidermoid carcinoma in maxilla.

Introduction Vertical maxillary excess, a common orthodontic problem that leads to long faces and open bites, can be repositioned with a Le Fort I osteotomy. However, the Le Fort I osteotomy poses the risk of a variety of complications including descending palatine artery (DPA) injury. Although several Le Fort I osteotomy modifications were reported to avoid complications associated with this osteotomy, only a few of such studies were conducted in Japan, and details remain scarce. Patients and methods We performed a literature review regarding modifications of Le Fort I osteotomies, including Le Fort I with a horseshoe osteotomy, modified horseshoe osteotomy, unilateral horseshoe osteotomy, pyramidal osteotomy, and U-shaped osteotomy. We identified eight relevant studies conducted in Japan; one study did not provide the number of patients examined. The 77 patients (seven studies) with vertical maxillary excess who underwent orthognathic surgery were ≥17 years old. Discussion There were no severe complications after the modified Le Fort I osteotomies. The postoperative maxillary changes obtained by the conventional horseshoe, modified horseshoe, unilateral type of horseshoe, pyramidal, and U-shaped osteotomies were nearly repositioned to the planned position and remained stable for ≥12 months post-surgery. Conclusion Our review indicates that preserving the DPA can lower the incidence of intra- and post-operative complications. Each modification of the Le Fort I osteotomy (i.e., conventional horseshoe, modified horseshoe, unilateral horseshoe, pyramidal, and U-shaped osteotomy) has its respective advantages and indications., Highlights • Vertical maxillary excess (excessive maxilla growth) impairs functions/aesthetics • Vertical maxillary excess is treated with a conventional Le Fort I osteotomy. • Extensive bone removal for the descending palatine artery with impaction is needed. • Various modifications of Le Fort I provide better maxilla repositioning. • Modifications can preserve the DP artery and minimize complications.

Gingival squamous cell carcinoma (SCC) frequently invades the maxillary or mandibular bone, and bone destruction is known as a key prognostic factor in gingival SCCs. Recently, Neurokinin 3 receptor (NK-3R), the receptor ligand for NK-3, which is a member of the tachykinin family expressed in the central nervous system, was identified through pathway analysis as a molecule expressed in osteoclasts induced by the hedgehog signal. Although the expression of NK-3R has been detected in osteoclast and SCC cells at the bone invasion front, the relationship between NK-3R expression and the prognosis of gingival SCC patients remains unclear. In the present study, we retrospectively reviewed 27 patients with gingival SCC who had undergone surgery with curative intent. Significantly higher NK-3R expression in tumor cells was found in a case of jawbone invasion than in a case of exophytic poor jawbone invasion. On the other hand, no significant association was observed between NK-3R tumor-positive cases and tumor size, TNM stage, or tumor differentiation. The survival rate tended to be lower in NK-3R tumor-positive cases, but not significantly. However, the disease-specific survival rate was significantly lower in patients with a large number of NK-3R-positive osteoclasts than in those with a small number of them at the tumor bone invasion front. Our results suggest that NK-3R signaling in the gingival SCC bone microenvironment plays an important role in tumor bone destruction and should be considered a potential therapeutic target in advanced gingival SCC with bone destruction.

Highlights • A deep overbite is defined as a vertical overlap of the upper and lower incisors. • Problems related to deep overbite can include soft tissue trauma. • It is difficult to recover functions with ordinary prosthetic therapy alone in patients with severe deep overbite with dentofacial deformities. • Comprehensive surgical orthodontic treatment is indicated for such patients., Introduction Patients with severe overbite in middle age often undergo prosthetic treatment without a diagnosis of dentofacial deformity, but soft tissue trauma can occur in such patients due to the lack of inter-occlusal space. Comprehensive surgical orthodontic treatment and prosthetic treatment are indicated to correct the overbite and soft tissue injury for such patients. Presentation of case We report the cases of two middle-aged patients with dentofacial deformity and severe overbite without molar support. In both cases, prosthetic treatment had been performed for many years without any improvement of the occlusion. Case 1: A 47-year-old Japanese man had a maxillary incisor protrusion and reduced lower anterior facial height profile with the left mandibular molars lost due to periodontal disease. After preoperative orthodontic treatment and occlusal elevation in the molar teeth using an implant prosthesis, a sagittal split ramus osteotomy (SSRO) was performed. Case 2: A 57-year-old Japanese woman had mandibular retrognathia with maxilla and mandibular-arch length discrepancy. The left mandibular molars needed to be extracted due to periodontal disease. After preoperative orthodontic treatment and reconstruction of the molar occlusion using an implant prosthesis, three-segment Le Fort I osteotomy and SSRO were performed. Discussion Malocclusion with dentofacial deformity is a risk factor for severe deep overbite or other occlusion collapse. Conclusion In middle-aged patients with deep overbite with missing molar teeth, we should consider both prosthodontic treatment and comprehensive dental therapy, including orthognathic surgery.

BACKGROUND/AIM We have previously reported that treatment of pancreatic cancer cells with active hexose-correlated compound (AHCC), an extract of a basidiomycete mushroom, decreases the levels of tumor-associated proteins including heat-shock protein 27 (HSP27), heat shock factor 1 (HSF1) and sex-determining region Y-box 2 (SOX2). The transmembrane glycoprotein, CUB domain-containing protein 1 (CDCP1) has been reported to be up-regulated in various cancers, and be associated with invasion and metastasis. The aim of this study was to examine the effect of AHCC on the expression of CDCP1 in KLM1-R cells. MATERIALS AND METHODS Gemcitabine-resistant pancreatic cancer cells (KLM1-R) were treated with AHCC (10 mg/ml) for 48 h. Western blot analysis of cell extracts with anti-CDCP1 or anti-actin antibodies was performed to assess the expression of CDCP1. RESULTS Expression of CDCP1 was reduced by AHCC treatment of KLM1-R cells, whereas expression of actin was not affected. The ratio of intensities of CDCP1/actin in AHCC-treated KLM1-R cells was significantly suppressed (p

Background The periodontal ligament (PDL), which surrounds the tooth root, contains mesenchymal stem cells (MSCs) capable of differentiating into osteoblasts, cementoblasts, and fibroblasts under normal conditions. These MSCs are thought to have important roles in the repair and regeneration of injured periodontal tissues. However, since there is no useful marker for MSCs in the PDL, the characteristics and distributions of these cells remain unclear. Gli1, an essential hedgehog signaling transcription factor, functions in undifferentiated cells during embryogenesis. Previous studies have demonstrated that the dental epithelial and mesenchymal cells positive for Gli1 in developing teeth have stem cell properties, including the ability to form colonies and pluripotency. Therefore, the focus of this review is the stem cell properties of Gli1-positive cells in the PDL, with an emphasis on the differentiation ability of osteoblasts for the regeneration of periodontal tissues. Highlight Lineage tracing analysis identified Gli1-positive PDL cells as MSCs that contribute to the formation of periodontal tissues and can regenerate alveolar bone. Conclusion Gli1 is a potential stem cell marker in the PDL. A more definitive understanding of the functions of Gli1-positive cells could be useful for the development of regenerative methods using the MSCs in the PDL.

Sonic hedgehog (Shh) is a secreted protein with important roles in mammalian embryogenesis. During tooth development, Shh is primarily expressed in the dental epithelium, from initiation to the root formation stages. A number of studies have analyzed the function of Shh signaling at different stages of tooth development and have revealed that Shh signaling regulates the formation of various tooth components, including enamel, dentin, cementum, and other soft tissues. In addition, dental mesenchymal cells positive for Gli1, a downstream transcription factor of Shh signaling, have been found to have stem cell properties, including multipotency and the ability to self-renew. Indeed, Gli1-positive cells in mature teeth appear to contribute to the regeneration of dental pulp and periodontal tissues. In this review, we provide an overview of recent advances related to the role of Shh signaling in tooth development, as well as the contribution of this pathway to tooth homeostasis and regeneration.

Bone fracture healing involves the combination of intramembranous and endochondral ossification. It is known that Indian hedgehog (Ihh) promotes chondrogenesis during fracture healing. Meanwhile, Sonic hedgehog (Shh), which is involved in ontogeny, has been reported to be involved in fracture healing, but the details had not been clarified. In this study, we demonstrated that Shh participated in fracture healing. Six-week-old Sprague–Dawley rats and Gli-CreERT2; tdTomato mice were used in this study. The right rib bones of experimental animals were fractured. The localization of Shh and Gli1 during fracture healing was examined. The localization of Gli1 progeny cells and osterix (Osx)-positive cells was similar during fracture healing. Runt-related transcription factor 2 (Runx2) and Osx, both of which are osteoblast markers, were observed on the surface of the new bone matrix and chondrocytes on day seven after fracture. Shh and Gli1 were co-localized with Runx2 and Osx. These findings suggest that Shh is involved in intramembranous and endochondral ossification during fracture healing.

Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of SHH expression appear to correlate with cancer progression. However, the role of SHH in the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is still unclear. No studies have compared the expression of SHH in different subtypes of OSCC and focused on the relationship between the tumor parenchyma and stroma. In this study, we analyzed SHH and expression of its receptor, Patched-1 (PTCH), in the TME of different subtypes of OSCC. Fifteen endophytic-type cases (ED type) and 15 exophytic-type cases (EX type) of OSCC were used. H&amp, E staining, immunohistochemistry (IHC), double IHC, and double-fluorescent IHC were performed on these samples. ED-type parenchyma more strongly expressed both SHH and PTCH than EX-type parenchyma. In OSCC stroma, CD31-positive cancer blood vessels, CD68- and CD11b-positive macrophages, and &alpha, smooth muscle actin-positive cancer-associated fibroblasts partially expressed PTCH. On the other hand, in EX-type stroma, almost no double-positive cells were observed. These results suggest that autocrine effects of SHH induce cancer invasion, and paracrine effects of SHH govern parenchyma-stromal interactions of OSCC. The role of the SHH pathway is to promote growth and invasion.

Low-intensity pulsed ultrasound (LIPUS) has been used as an adjunct to fracture healing therapies, but the mechanisms underlying its action are not known. We reported that sonic hedgehog (SHH) signaling was activated in osteoblasts at the dynamic remodeling site of a bone fracture. Mechanical stimulation is a crucial factor in bone remodeling, and it is related to the primary cilia as a sensor of hedgehog signaling. Here we observed that LIPUS promoted callus formation in accord with Gli2-positive cells after 14 days at the mouse femur fractured site compared with a control group. An immunofluorescence analysis showed that the numbers of primary cilia and cilia/osterix double-positive osteoblasts were increased at the fracture site by LIPUS. LIPUS stimulated not only the number and the length of primary cilia, but also the levels of ciliated protein, Ift88 mRNA, and SHH, Gli1, and Gli2 in MC3T3-E1 cells. Further experiments revealed that LIPUS stimulated osteogenic differentiation in the presence of smoothened agonist (SAG) treatment. These results indicate that LIPUS stimulates osteogenic differentiation and the maturation of osteoblasts by a primary cilium-mediated activation of hedgehog signaling.

Introduction Mucoceles are mucous extravasation phenomena resulting from spontaneous ductal rupture or, less commonly, a traumatic cutting of a salivary excretory duct. Occasionally, the appearance of a mucocele closely resembles a neoplastic lesion, and it can be difficult to diagnose. Presentation of case A 74-year-old Japanese male patient was referred to our clinic with painless swelling related to the upper right canine-premolar area. Preoperative imaging of the lesion revealed that it was fluid-filled and the histopathological biopsy suggested a myxoid tumor. We excised the lesion with the patient under general anesthesia, using safety margins based on the histology of the biopsy specimen to reach the definitive diagnosis and treatment. The final pathological diagnosis was a mucocele in the vicinity with an aberrant small salivary gland. Follow-up visits showed complete healing of the epithelium, and no recurrence has been observed during the subsequent 30 months. Discussion In cases with a difficult definitive diagnosis based on medical history, diagnostic imaging and pathological examination, it is important to proceed carefully with the possibility of a tumor in mind. Conclusion This case emphasizes that some mucous cysts are challenging for clinicians in terms of diagnosis and treatment due to an uncommon presentation., Highlights • Mucoceles are relatively easily diagnosed with a clear clinical picture/history. • Mucocele often occurs on the lower lip due to frequent trauma from biting. • At an unusual site such as gingiva, it is likely to be diagnosed as a neoplasm. • We treated a maxillary gingiva mucocele initially diagnosed as a myxoid tumor.