Osteogenic potential for replacing cells in rat cranial defects implanted with a DNA/protamine complex paste.

Osteoinductive scaffolds are required for bone tissue engineering. The aim of the present study was to assess the osteoinductive capacity of deoxyribonucleic acid (DNA)/protamine complexes in a rat model of critical-size calvarial defects. In addition, we investigated whether cultured mesenchymal-like cells (DP-cells) outgrown from DNA/protamine complex engrafted defects could differentiate to become osteogenic cells in vitro. DNA/protamine complexes were prepared by reactions between DNA and protamine sulfate solutions with stirring. Critical-sized (8mm) calvarial defects were created in the central parietal bones of adult rats. Defects were either left empty or treated with DNA/protamine complex scaffolds. Subsequently, micro-computed tomography (micro-CT), histological, and immunohistochemical analyses were performed. Micro-CT and histological assays showed that DNA/protamine complex engrafted defects had enhanced bone regeneration. DP-cells were expanded from explants of DNA/protamine complex engrafted defects using an explant outgrowth culture system. Osteogenesis-related factors were assessed in DP-cells after treatment with an osteoblast-inducing reagent (OIR). After 3months, nearly complete healing was observed for DNA/protamine complex engrafted calvarial defects. Increased alkaline phosphatase (ALP) activity and Alizarin red staining were found for cultured DP-cells. These cells had high expression levels of osteogenic genes, including those for RUNX-2, ALP, osteopontin, and osteocalcin. These results indicated that DNA/protamine complexes could facilitate bone regeneration in calvarial defects. Moreover, in vitro osteogenic induction experiments showed that DP-cells outgrown from DNA/protamine engrafted defects had an osteogenic potential. Based on these results, we suggest that DNA/protamine complexes may recruit osteocompetent cells in these defects, where they differentiate to osteogenic cells.福岡歯科大学2015年

Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy

Astrocyte abnormalities have received great attention for their association with various diseases in the brain but not so much in the eye. Recent independent genome-wide association studies of glaucoma, optic neuropathy characterized by retinal ganglion cell (RGC) degeneration, and vision loss found that single-nucleotide polymorphisms near the ABCA1 locus were common risk factors. Here, we show that Abca1 loss in retinal astrocytes causes glaucoma-like optic neuropathy in aged mice. ABCA1 was highly expressed in retinal astrocytes in mice. Thus, we generated macroglia-specific Abca1-deficient mice (Glia-KO) and found that aged Glia-KO mice had RGC degeneration and ocular dysfunction without affected intraocular pressure, a conventional risk factor for glaucoma. Single-cell RNA sequencing revealed that Abca1 deficiency in aged Glia-KO mice caused astrocyte-triggered inflammation and increased the susceptibility of certain RGC clusters to excitotoxicity. Together, astrocytes play a pivotal role in eye diseases, and loss of ABCA1 in astrocytes causes glaucoma-like neuropathy

Osteogenic Evaluation of DNA/Protamine Complex Paste in Rat Cranial Defects

福岡歯科大学2013年

Successful Treatment of Mediastinal Unicentric Castleman’s Disease Using Video-Assisted Thoracoscopic Surgery with Preoperative Embolization

Unicentric Castleman’s disease is a rare, benign lymphoproliferative disorder that is curable with surgical resection. However, significant bleeding often occurs during surgery because of tumor hypervascularity. We herein present a case of hyaline-vascular-type mediastinal unicentric Castleman’s disease, successfully resected using video-assisted thoracoscopic surgery with preoperative embolization. In the present case, tumor hypervascularity and feeding vessels were revealed by computed tomography (CT), which led us to perform preoperative angiography and embolization to the tumor feeding arteries to reduce intraoperative bleeding. Castleman’s disease should be considered in the differential diagnosis of hypervascular mediastinal tumors. Tumor vascularity should be assessed prior to surgery, and preoperative embolization should be considered

Thermoelectric Properties of the As/P-Based Zintl Compounds EuIn2As2−xPx (X = 0 to 2) and SrSn2As2

Zintl compounds containing Sb have been studied extensively because of their promising thermoelectric properties. In this study, we prepared As/P-based Zintl compounds, EuIn2As2-xPx (x = 0 to 2) and SrSn2As2, and examined their potential for use as thermoelectric materials. These compounds show hole carrier concentrations of ~10^19 /cm3 for EuIn2As2-xPx and ~10^21 /cm3 for SrSn2As2 at 300 K. The high carrier concentration of SrSn2As2 is likely owing to self-doping by hole-donating Sn vacancies. The electrical power factor reaches ~1 mW/mK2 at ~600 K for EuIn2As2-xPx with x = 0.1 and 0.2. The lattice thermal conductivity is determined to be 1.6–2.0 W/mK for EuIn2As2 and SrSn2As2, and 2.8 W/mK for EuIn2P2 at 673 K. The dimensionless figure of merit reaches ZT = 0.29 at 773 K for EuIn2As2-xPx with x = 0.2. First-principles calculations show that EuIn2As2 and SrSn2As2 are topologically nontrivial materials with band inversion, while EuIn2P2 is a conventional semiconductor with a bandgap. The present study demonstrates that As/P-based Zintl compounds can also show promising thermoelectric properties, thus expanding the frontier for efficient thermoelectric materials

Astrocytes Protect Neurons against Methylmercury via ATP/P2Y₁ Receptor-Mediated Pathways in Astrocytes

<div><p>Methylmercury (MeHg) is a well known environmental pollutant that induces serious neuronal damage. Although MeHg readily crosses the blood-brain barrier, and should affect both neurons and glial cells, how it affects glia or neuron-to-glia interactions has received only limited attention. Here, we report that MeHg triggers ATP/P2Y₁ receptor signals in astrocytes, thereby protecting neurons against MeHg via interleukin-6 (IL-6)-mediated pathways. MeHg increased several mRNAs in astrocytes, among which IL-6 was the highest. For this, ATP/P2Y₁ receptor-mediated mechanisms were required because the IL-6 production was (i) inhibited by a P2Y₁ receptor antagonist, MRS2179, (ii) abolished in astrocytes obtained from P2Y₁ receptor-knockout mice, and (iii) mimicked by exogenously applied ATP. In addition, (iv) MeHg released ATP by exocytosis from astrocytes. As for the intracellular mechanisms responsible for IL-6 production, p38 MAP kinase was involved. MeHg-treated astrocyte-conditioned medium (ACM) showed neuro-protective effects against MeHg, which was blocked by anti-IL-6 antibody and was mimicked by the application of recombinant IL-6. As for the mechanism of neuro-protection by IL-6, an adenosine A₁ receptor-mediated pathway in neurons seems to be involved. Taken together, when astrocytes sense MeHg, they release ATP that autostimulates P2Y₁ receptors to upregulate IL-6, thereby leading to A₁ receptor-mediated neuro-protection against MeHg.</p> </div

MeHg-induced IL-6 mRNA upregulation and protein release from astrocytes.

<p>(<b>A</b>) Effect of MeHg on IL-6 mRNA expression in astrocytes. MeHg (1–3 µM) transiently increased IL-6 expression and the induction peak was observed at 2 hr exposure. Low concentration of MeHg (0.1 µM) had no effect on IL-6 expression. *P<0.05 and **P<0.01 vs. control. (<b>B</b>) MeHg-induced IL-6 protein production to the supernatant from astrocytes. MeHg (1 or 3 µM, 12 or 24 hr) induced IL-6 production. The 12-hr exposure exhibited a lower level of IL-6 release than that with 24-hr exposure of MeHg.</p