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Ameloblastoma is an odontogenic benign tumor that occurs in the jawbone, which invades bone and reoccurs locally. This tumor is treated by wide surgical excision and causes various problems, including changes in facial countenance and mastication disorders. Ameloblastomas have abundant tumor stroma, including fibroblasts and immune cells. Although cell-to-cell interactions are considered to be involved in the pathogenesis of many diseases, intercellular communications in ameloblastoma have not been fully investigated. In this study, we examined interactions between tumor cells and stromal fibroblasts via soluble factors in ameloblastoma. We used a human ameloblastoma cell line (AM-3 ameloblastoma cells), human fibroblasts (HFF-2 fibroblasts), and primary-cultured fibroblasts from human ameloblastoma tissues, and analyzed the effect of ameloblastoma-associated cell-to-cell communications on gene expression, cytokine secretion, cellular motility and proliferation. AM-3 ameloblastoma cells secreted higher levels of interleukin (IL)-1α than HFF-2 fibroblasts. Treatment with conditioned medium from AM-3 ameloblastoma cells upregulated gene expression and secretion of IL-6 and IL-8 of HFF-2 fibroblasts and primary-cultured fibroblast cells from ameloblastoma tissues. The AM3-stimulated production of IL-6 and IL-8 in fibroblasts was neutralized by pretreatment of AM-3 cells with anti-IL-1α antibody and IL-1 receptor antagonist. Reciprocally, cellular motility of AM-3 ameloblastoma cells was stimulated by HFF-2 fibroblasts in IL-6 and IL-8 dependent manner. In conclusion, ameloblastoma cells and stromal fibroblasts behave interactively via these cytokines to create a microenvironment that leads to the extension of ameloblastomas., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Ameloblastoma has a high risk of bone invasion and local recurrence. However, the mechanisms of bone invasion in ameloblastoma remain unclear. In this study, we established an experimental model for matrix metalloproteinase (MMP) induction and osteoclastogenesis using ameloblastoma-derived cells., Study Design: We established an ameloblastoma-derived cell line without viral genes and analyzed the expression of all Wnt and Frizzled members and MMPs by real-time reverse transcription-polymerase chain reaction, and analyzed the activity of MMP-2 and MMP-9 by the in-gel-gelatinase assay., Results: AM-3, newly established ameloblastoma-derived cells retained the morphology of primary-cultured ameloblastoma cells. AM-3 cells overexpressed the messenger RNA of Wnt-5a, Frizzled-2, MMP-2, and MMP-9 and showed the potential of osteoclastogenesis. In addition, Wnt-3a-treatment induced expression and activation of MMP-9 in AM-3 cells., Conclusions: Our study suggests that AM-3 cells retained the characteristics of ameloblastoma, without acquiring typical features of cancer cells. Furthermore, Wnt signaling induced MMP-9 in ameloblastoma cells., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene encoding chorein. Although a deficiency in chorein function leads to apoptosis of striatal neurons in ChAc model mouse, its detailed subcellular localization and physiological role remain unclear. In this study, we produced two anti-chorein polyclonal antibodies and examined the intracellular localization of endogenous chorein in neuronal cells. Immunocytochemically, chorein was observed in the termini of extended neurites and partially colocalized with synaptotagmin I in differentiated PC12 cells. Subcellular localization analysis by sucrose density gradient fractionation showed that chorein and synaptotagmin I were located in dense-core vesicles (DCVs), which contain dopamine. In addition, PC12 cells stably expressing carboxyterminal fragment of chorein increased K(+)-induced dopamine release. Taken together, these results suggest that chorein is involved in exocytosis of DCV., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We found reduced locomotor activity (LA) under fasting in systemic carnitine-deficient juvenile visceral steatosis (jvs(-/-)) mice. When food was withdrawn at 8:00 a.m. (lights-off at 7:00 p.m., 12h/cycle), the nocturnal LA of jvs(-/-) mice was much less than the control (jvs(+/+) and jvs(+/-)) mice. LA recovered under carnitine or sucrose administration, but not under medium-chain triglyceride. In addition, fasted jvs(-/-) mice, without any energy supply, were activated by modafinil, a stimulator of the dopamine pathway. These results suggest that the reduced LA is not adequately explained by energy deficit. As the fasted jvs(-/-) mice showed lower body core temperature (BT), we examined the central nervous system regulating LA and BT. We found lower percentage of c-Fos positive orexin neurons in the lateral hypothalamus and reduced orexin-A concentration in the cerebrospinal fluid of fasted jvs(-/-) mice. Sleep analysis revealed that fasted jvs(-/-) mice had disruption of prolonged wakefulness, with a higher frequency of brief episodes of non-REM sleep during the dark period than fasted jvs(+/+) mice. These results strongly suggest that the reduced LA in fasted jvs(-/-) mice is related to the inhibition of orexin neuronal activity.

Background/aims: Mutations in SLC25A13, encoding the mitochondrial aspartate-glutamate carrier citrin, cause adult-onset type II citrullinemia (CTLN2) in humans. We have previously reported that although citrin-knockout (Ctrn-/-) mice fail to display symptoms of CTLN2, liver perfusion revealed a deficit in ureogenesis from ammonia accompanied by an increase in the perfusate lactate-to-pyruvate (L/P) ratio. The present study explores the effects of pyruvate, aspartate and citrate on improving the abnormalities observed in the Ctrn-/- liver., Methods: We measured the rate of ureogenesis from ammonium chloride using the liver-perfusion system., Results: Pyruvate infusion lowered the L/P ratio and corrected the deficit in ureogenesis in the Ctrn-/- liver. This effect was found to be dose-dependent in both instances. Phenazine methosulfate, a cytosolic oxidant, also improved the rate of ureogenesis in the Ctrn-/- liver and led to a fall in the L/P ratio. The addition of aspartate or citrate did not change either the rate of ureogenesis or the L/P ratio in the Ctrn-/- liver., Conclusions: Citrin deficiency disturbs urea synthesis primarily as a result of an elevated cytosolic NADH/NAD+ ratio owing to limited reoxidation of reducing equivalents. Clinically, pyruvate may have a therapeutic benefit for CTLN2 patients.