Does a Vascularized Fibula Free Bone Grafted Immediately After Hemimandibulectomy in a Child Grow or Relapse During Adolescence?

For young growing children before the end of skeletal maturity, the growth activity of the grafted bone after hemimandibulectomy is not well-known. After an adolescence, such a patient may have facial deformity because the anterior growth point of the mandible is in the condylar neck. A 13-year-old boy was performed hemimandibulectomy with immediate mandibular reconstruction by fibula free flap (FFF) because of a huge ameloblastic fibroma. The authors evaluated the length of FFF on the images of computed tomography (CT) at 5 and 60 months after the operation and compared them by calculating growth rates. Five years after surgery, his facial appearance was symmetry and mandibular function was satisfaction. Although the mandibular bone in the contralateral side grew during 5-year follow-up, the vascularized FFF grafted in the child patient did not significantly grow. Moreover, spontaneous regeneration (SR) and the gradual osteosclerosis were confirmed on the left distal edge of the FFF on the CT imaging. The arrival of SR at the left distal edge of the FFF was considered a part of the reason to compensate the unchanging growth rate of the grafted FFF and contribute for the postoperative good functional and esthetic results.

Clinical Study of 597 Oral Squamous Cell Carcinomas in Our Department - Especially about 318 Tongue Carcinoma.

This clinico-statistical study includes 597 cases of oral squamous cell carcinoma treated at the Maxillofacial Surgery Section of Tokyo Medical and Dental University between January 2002 and December 2011. There were 373 male and 224 female patients (male to female ratio, 1.7 : 1), and the median age was 67 years. The tongue (53.3%) was the most commonly affected site. The 5-year disease-specific survival rate was 84.8%. Survival rates by clinical stage were as follows : Stage 1, 92.1% (n=195).; Stage , 86.0% (n = 221) ; Stage III, 77.7% (n=65) ; and Stage IV, 73.8% (n =116). Survival rates by primary site were as follows: tongue, 85.4% (n=318) ; lower gingiva, 82.8% (n =114) upper gingiva, 83.7% (n=59) ; buccal mucosa, 89.1% (n 54) ; oral floor, 81.4% (n=49) ; and hard palate, 100% (n=3). According to clinical growth patterns of Stage I / I tongue cancer cases, the 5-year disease-specific survival rate was significantly higher for patients with the exophytic/superficial type (97.3%, n =173) than for those with the endophytic type (77.5%, n=145). Among Stage I/II tongue cancer cases, the corresponding survival rate was significantly higher for patients who had not previously undergone invasive treatments (n=201), such as tooth extraction, compared to those who had previously done so (n=54) (92.7% and 79.7%, respectively). In addition, the incidence of secondary cervical lymph node metastasis was significantly higher in patients who had previously undergone invasive treatments.

Nanogel-based scaffold delivery of prostaglandin E(2) receptor-specific agonist in combination with a low dose of growth factor heals critical-size bone defects in mice.

OBJECTIVE: Regeneration of bone requires the combination of appropriate drugs and an appropriate delivery system to control cell behavior. However, the delivery of multiple drugs to heal bone is complicated by the availability of carriers. The aim of this study was to explore a new system for delivery of a selective EP4 receptor agonist (EP4A) in combination with low-dose bone morphogenetic protein 2 (BMP-2). METHODS: Combined delivery of EP4A and BMP-2 was carried out with a nanogel-based scaffold in the shape of a disc, to repair critical-size circle-shaped bone defects in calvariae that otherwise did not heal spontaneously. RESULTS: Combination treatment with EP4A and low-dose BMP-2 in nanogel efficiently activated bone cells to regenerate calvarial bone by forming both outer and inner cortical plates as well as bone marrow tissue to regenerate a structure similar to that of intact calvaria. EP4A enhanced low-dose BMP-2-induced cell differentiation and activation of transcription events in osteoblasts. CONCLUSION: These data indicate that combined delivery of EP4A and low-dose BMP-2 via nanogel-based hydrogel provides a new system for bone repair.

[Clinicopathological study of calcifying cystic odontogenic tumors].

Calcifying cystic odontogenic tumors are benign tumors, characterized by the presence of ghost cells and calcified materials. We evaluated clinical characteristics of calcifying cystic odontogenic tumors in 21 cases at the Maxillofacial Surgery, Tokyo Medical and Dental University Hospital, between January 1979 and December 2006. Of the 21 lesions that were studied, 12 were observed in male patients, and 9 in female patients. The median age was 13.0 years (range, 4-69 years). Of the 21 lesions, 11 were located in the maxilla (intraosseous), 9 in the mandible (intraosseous), and 1 in the lower gingiva (extraosseous). Radiographically, 18 lesions appeared as unilocular radiolucencies, and 2 lesions as multilocular radiolucencies. Impacted teeth were observed in 15 cases. In 20 cases, the lesions were treated by enucleation. The follow-up duration ranged from 2 years, 5 months to 28 years, 8 months, and in 1 case, the lesion recurred and showed a malignant transformation 2 years 10 months after the treatment. Histopathologically, the lining epithelium consisted of cuboidal or columnar odontogenic cells. Ghost cells were frequently calcified, and the tissue was hardened. In 14 cases, the tumor was associated with odontoma.

Dok-1 and Dok-2 deficiency induces osteopenia via activation of osteoclasts.

Osteoporosis causes fractures that lead to reduction in the quality of life and it is one of the most prevalent diseases as it affects approximately 10% of the population. One of the important features of osteoporosis is osteopenia. However, its etiology is not fully elucidated. Dok-1 and Dok-2 are adaptor proteins acting downstream of protein tyrosine kinases that are mainly expressed in the cells of hematopoietic lineage. Although these proteins negatively regulate immune system, their roles in bone metabolism are not understood. Here, we analyzed the effects of Dok-1 and Dok-2 double-deficiency on bone. Dok-1/2 deficiency reduced the levels of trabecular and cortical bone mass compared to wildtype. In addition, Dok-1/2 deficiency increased periosteal perimeters and endosteal perimeters of the mid shaft of long bones. Histomorphometric analysis of the bone parameters indicated that Dok-1/2 deficiency did not significantly alter the levels of bone formation parameters including mineralizing surface/bone surface (MS/BS), mineral apposition rate (MAR) and bone formation rate (BFR). In contrast, Dok-1/2 deficiency enhanced the levels of bone resorption parameters including osteoclast number (N.Oc/BS) and osteoclast surface (Oc.S/BS). Analyses of individual osteoclastic activity indicated that Dok-1/2 deficiency enhanced pit formation. Systemically, Dok-1/2 deficiency increased the levels of urinary deoxypyridinoline (Dpyr). Search for the target point of the Dok-1/2 deficiency effects on osteoclasts identified that the mutation enhanced sensitivity of osteoclast precursors to macrophage colony-stimulating factor. These data revealed that Dok-1 and Dok-2 deficiency induces osteopenia by activation of osteoclasts.

The rice ethylene response factor OsERF83 positively regulates disease resistance to Magnaporthe oryzae.

Rice blast caused by Magnaporthe oryzae is one of the most destructive diseases of rice (Oryza sativa) worldwide. Here, we report the identification and functional characterization of a novel ethylene response factor (ERF) gene, OsERF83, which was expressed in rice leaves in response to rice blast fungus infection. OsERF83 expression was also induced by treatments with methyl jasmonate, ethephon, and salicylic acid, indicating that multiple phytohormones could be involved in the regulation of OsERF83 expression under biotic stress. Subcellular localization and transactivation analyses demonstrated that OsERF83 is a nucleus-localized transcriptional activator. A gel-shift assay using recombinant OsERF83 protein indicated that, like other ERFs, it binds to the GCC box. Transgenic rice plants overexpressing OsERF83 exhibited significantly suppressed lesion formation after rice blast infection, indicating that OsERF83 positively regulates disease resistance in rice. Genes encoding several classes of pathogenesis-related (PR) proteins, including PR1, PR2, PR3, PR5, and PR10, were upregulated in the OsERF83ox plants. Taken together, our findings show that OsERF83 is a novel ERF transcription factor that confers blast resistance by regulating the expression of defense-related genes in rice.

JunD suppresses bone formation and contributes to low bone mass induced by estrogen depletion.

JunD is an activator protein-1 (AP-1) component though its function in skeletal system is still not fully understood. To elucidate the role of JunD in the regulation of bone metabolism, we analyzed JunD-deficient mice. JunD deficiency significantly increased bone mass and trabecular number. This bone mass enhancement was due to JunD deficiency-induced increase in bone formation activities in vivo. Such augmentation of bone formation was associated with simultaneous increase in bone resorption while the former was dominant over the latter as accumulation of bone mass occurred in JunD-deficient mice. In a pathological condition relevant to postmenopausal osteoporosis, ovariectomy reduced bone mass in wild type (WT) mice as known before. Interestingly, JunD deficiency suppressed ovariectomy-induced increase in bone resorption and kept high bone mass. In addition, JunD deficiency also enhanced new bone formation after bone marrow ablation. Examination of molecular bases for these observations revealed that JunD deficiency enhanced expression levels of c-jun, fra-1, and fra-2 in bone in conjunction with elevated expression levels of runx2, type I collagen, and osteocalcin. Thus, JunD is involved in estrogen depletion-induced osteopenia via its action to suppress bone formation and to enhance bone resorption.

Type VI collagen deficiency induces osteopenia with distortion of osteoblastic cell morphology.

Bone consists of type I collagen as a major protein with minor various matrix proteins. Type VI collagen is one of bone matrix proteins but its function is not known. We therefore examined the effects of type VI collagen deficiency on bone. 3D-µCT analysis revealed that type VI collagen deficiency reduced cancellous bone mass. Cortical bone mass was not affected. Type VI collagen deficiency distorted the shape of osteoblasts both in the cancellous bone and in the cambium layer of periosteal region. Furthermore, type VI collagen deficiency disorganized collagen arrangement. These data indicate that type VI collagen contributes to maintain bone mass.

Angiotensin II type 2 receptor blockade increases bone mass.

Renin angiotensin system (RAS) regulates circulating blood volume and blood pressure systemically, whereas RAS also plays a role in the local milieu. Previous in vitro studies suggested that RAS may be involved in the regulation of bone cells. However, it was not known whether molecules involved in RAS are present in bone in vivo. In this study, we examined the presence of RAS components in adult bone and the effects of angiotensin II type 2 (AT2) receptor blocker on bone mass. Immunohistochemistry revealed that AT2 receptor protein was expressed in both osteoblasts and osteoclasts. In addition, renin and angiotensin II-converting enzyme were expressed in bone cells in vivo. Treatment with AT2 receptor blocker significantly enhanced the levels of bone mass, and this effect was based on the enhancement of osteoblastic activity as well as the suppression of osteoclastic activity in vivo. These results indicate that RAS components are present in adult bone and that blockade of AT2 receptor results in alteration in bone mass.