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Nagasaki, Japan

Nagasaki University is a national university of Japan. Its nickname is Chōdai . The main campus is located in Bunkyo-machi, Nagasaki City, Nagasaki Prefecture, Japan. Wikipedia.

Komori T.,Nagasaki University
Cell and Tissue Research | Year: 2010

RUNX2 is a multifunctional transcription factor that controls skeletal development by regulating the differentiation of chondrocytes and osteoblasts and the expression of many extracellular matrix protein genes during chondrocyte and osteoblast differentiation. This transcription factor plays a major role at the late stage of chondrocyte differentiation: it is required for chondrocyte maturation and regulates Col10a1 expression in hypertrophic chondrocytes and the expression of Spp1, Ibsp, and Mmp13 in terminal hypertrophic chondrocytes. It is essential for the commitment of pluripotent mesenchymal cells to the osteoblast lineage. During osteoblast differentiation, RUNX2 upregulates the expression of bone matrix protein genes including Col1a1, Spp1, Ibsp, Bglap, and Fn1 in vitro and activates many promoters including those of Col1a1, Col1a2, Spp1, Bglap, and Mmp13. However, overexpression of Runx2 inhibits osteoblast maturation and reduces Col1a1 and Bglap expression. The inhibition of RUNX2 in mature osteoblasts does not reduce the expression of Col1a1 and Bglap in mice. Thus, RUNX2 directs pluripotent mesenchymal cells to the osteoblast lineage, triggers the expression of major bone matrix protein genes, and keeps the osteoblasts in an immature stage, but does not play a major role in the maintenance of the expression of Col1a1 or Bglap in mature osteoblasts. During bone development, RUNX2 induces osteoblast differentiation and increases the number of immature osteoblasts, which form immature bone, whereas Runx2 expression has to be downregulated for differentiation into mature osteoblasts, which form mature bone. During dentinogenesis, Runx2 expression is downregulated, and RUNX2 inhibits the terminal differentiation of odontoblasts. © 2009 Springer-Verlag. Source

Kawasaki E.,Nagasaki University
Endocrine Journal | Year: 2012

Zinc is essential for the proper storage, secretion, and the action of insulin and is transported from cytoplasm to insulin secretory granules in the pancreatic β-cells by SLC30A zinc transporters (ZnT). ZnT8 is specifically expressed in the pancreatic β-cells and has been identified as a novel target autoantigen in patients with type 1 diabetes. Autoantibodies to ZnT8 (ZnT8A) are detected in 50-60% of Japanese patients with acute-onset and 20% with slow-onset type 1 diabetes. Furthermore, humoral autoreactivity to ZnT8 is unique in terms of a key determinant, which is not reported on other islet autoantigens such as insulin, glutamic acid decarboxylase, or the protein tyrosine phosphatase-related molecules IA-2. Type 2 diabetes-associated nonsynonymous single nucleotide polymorphism in SLC30A8 (the gene of ZnT8), rs13266634 (Arg325Trp), modulates ZnT8A specificities thereby indicating that this amino acid substitution has the critical role in antibody binding. The humoral autoreactivity to ZnT8 depends on the clinical phenotype, which may provide clues to understand the role of this protein in the pathogenesis of type 1 diabetes. ©The Japan Endocrine Society. Source

Komori T.,Nagasaki University
Advances in Experimental Medicine and Biology | Year: 2010

Runx2 protein is first detected in preosteoblasts and the expression is upregulated in immature osteoblasts but downregulated in mature osteoblasts. Runx2 is the first transcription factor required for determination of the osteoblast lineage while Sp7 and canonical Wnt-signaling further direct the fate of mesenchymal cells to osteoblasts blocking their differentiation into chondrocytes. Runx2 induces the differentiation of multipotent mesenchymal cells into immature osteoblasts directing the formation of immature bone but Runx2 inhibits osteoblast maturation and mature bone formation. Normally the protein level of Runx2 in osteoblasts reduces during bone development and osteoblasts acquire mature phenotypes which are required for mature bone formation. Furthermore Runx2 triggers the expression of major bone matrix genes during the early stages of osteoblast differentiation but Runx2 is not essential for the maintenance of these gene expressions in mature osteoblasts. © 2010 Springer Science+Business Media LLC. Source

Komori T.,Nagasaki University
Journal of Cellular Biochemistry | Year: 2011

RUNX2 is an essential transcription factor for osteoblast differentiation and chondrocyte maturation. SP7, another transcription factor, is required for osteoblast differentiation. Major signaling pathways, including FGF, Wnt, and IHH, also play important roles in skeletal development. RUNX2 regulates Sp7 expression at an early stage of osteoblast differentiation. FGF2 upregulates Runx2 expression and activates RUNX2, and gain-of-function mutations of FGFRs cause craniosynostosis and limb defect with upregulation of Runx2 expression. Wnt signaling upregulates Runx2 expression and activates RUNX2, and RUNX2 induces Tcf7 expression. IHH is required for Runx2 expression in osteoprogenitor cells during endochondral bone development, and RUNX2 directly regulates Ihh expression in chondrocytes. Thus, RUNX2 regulates osteoblast differentiation and chondrocyte maturation through the network with SP7 and with FGF, Wnt, and IHH signaling pathways during skeletal development. © 2010 Wiley-Liss, Inc. Source

Ito M.,Nagasaki University
Journal of Bone and Mineral Metabolism | Year: 2011

Advances in bone imaging techniques have provided tools for analyzing bone structure at the macro-, micro- and nano-level. Quantitative assessment of macrostructure can be achieved using dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), particularly volumetric quantitative CT (vQCT). In vivo quantitative techniques for assessing the microstructure of trabecular bone non-invasively and non-destructively include high-resolution CT (HR-CT) and high-resolution magnetic resonance (HR-MR). Compared withMRimaging, CT-based techniques have the advantage of directly visualizing the bone in the axial skeleton, with high spatial resolution, but the disadvantage of delivering a considerable radiation dose. Micro-CT (lCT), which provides a higher resolution of the microstructure and is principally applicable in vitro, has undergone technological advances such that it is now able to elucidate the physiological skeletal change mechanisms associated with aging and determine the effects of therapeutic intervention on the bone microstructure. In particular, synchrotron lCT (SR-CT) provides a more detailed view of trabecular structure at the nano-level. For the assessment of hip geometry, DXA-based hip structure analysis (HSA) and CT-based HSA have been developed. DXA-based HSA is a convenient tool for analyzing biomechanical properties and for assuming cross-sectional hip geometry based on two-dimensional (2D) data, whereas CTbased HSA provides these parameters three-dimensionally in robust relationship with biomechanical properties, at the cost of greater radiation exposure and the lengthy time required for the analytical procedure. Further progress in bone imaging technology is promising to bring new aspects of bone structure in relation to bone strength to light, and to establish a means for analyzing bone structural properties in the everyday clinical setting. © The Japanese Society for Bone and Mineral Research and Springer 2011. Source

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