457 results on '"Naoyuki Takahashi"'
Search Results
2. Microfluidic platform for the reproduction of hypoxic vascular microenvironments
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Naoyuki Takahashi, Daisuke Yoshino, Ryuji Sugahara, Satomi Hirose, Kazuki Sone, Jean-Paul Rieu, and Kenichi Funamoto
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Medicine ,Science - Abstract
Abstract Vascular endothelial cells (ECs) respond to mechanical stimuli caused by blood flow to maintain vascular homeostasis. Although the oxygen level in vascular microenvironment is lower than the atmospheric one, the cellular dynamics of ECs under hypoxic and flow exposure are not fully understood. Here, we describe a microfluidic platform for the reproduction hypoxic vascular microenvironments. Simultaneous application of hypoxic stress and fluid shear stress to the cultured cells was achieved by integrating a microfluidic device and a flow channel that adjusted the initial oxygen concentration in a cell culture medium. An EC monolayer was then formed on the media channel in the device, and the ECs were observed after exposure to hypoxic and flow conditions. The migration velocity of the ECs immediately increased after flow exposure, especially in the direction opposite to the flow direction, and gradually decreased, resulting in the lowest value under the hypoxic and flow exposure condition. The ECs after 6-h simultaneous exposure to hypoxic stress and fluid shear stress were generally aligned and elongated in the flow direction, with enhanced VE-cadherin expression and actin filament assembly. Thus, the developed microfluidic platform is useful for investigating the dynamics of ECs in vascular microenvironments.
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- 2023
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3. P21-activated kinase regulates oxygen-dependent migration of vascular endothelial cells in monolayers
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Satomi Hirose, Yugo Tabata, Kazuki Sone, Naoyuki Takahashi, Daisuke Yoshino, and Kenichi Funamoto
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collective cell migration ,hypoxia ,vascular endothelial monolayer ,microfluidic device ,p21-activated kinase ,Cytology ,QH573-671 - Abstract
The collective migration of vascular endothelial cells plays important roles in homeostasis and angiogenesis. Oxygen tension in vivo is a key factor affecting the cellular dynamics. We previously reported hypoxic conditions promote the internalization of vascular endothelial (VE)-cadherin and increase the collective migration of vascular endothelial cells. However, the mechanism through which cells regulate collective migration as affected by oxygen tension is not fully understood. Here, we investigated oxygen-dependent collective migration, focusing on intracellular protein p21-activated kinase (PAK) and hypoxia-inducing factor (HIF)-1α. The results indicate that the oxygen-dependent variation of the migration speed of vascular endothelial cells is mediated by the regulation of VE-cadherin through the PAK pathway, as well as other mechanisms via HIF-1α, especially under extreme hypoxic conditions.
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- 2021
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4. Osteogenic Factor Runx2 Marks a Subset of Leptin Receptor-Positive Cells that Sit Atop the Bone Marrow Stromal Cell Hierarchy
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Mengyu Yang, Atsushi Arai, Nobuyuki Udagawa, Toru Hiraga, Zhao Lijuan, Susumu Ito, Toshihisa Komori, Takeshi Moriishi, Koichi Matsuo, Kouji Shimoda, Ali H. Zahalka, Yasuhiro Kobayashi, Naoyuki Takahashi, and Toshihide Mizoguchi
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Medicine ,Science - Abstract
Abstract Bone marrow mesenchymal stem and progenitor cells (BM-MSPCs) maintain homeostasis of bone tissue by providing osteoblasts. Although several markers have been identified for labeling of MSPCs, these labeled cells still contain non-BM-MSPC populations. Studies have suggested that MSPCs are observed as leptin receptor (LepR)-positive cells, whereas osteoblasts can be classified as positive for Runx2, a master regulator for osteoblastogenesis. Here, we demonstrate, using Runx2-GFP reporter mice, that the LepR-labeled population contains Runx2-GFPlow sub-population, which possesses higher fibroblastic colony-forming units (CFUs) and mesensphere capacity, criteria for assessing stem cell activity, than the Runx2-GFP− population. In response to parathyroid hormone (PTH), a bone anabolic hormone, LepR+Runx2-GFPlow cells increase Runx2 expression and form multilayered structures near the bone surface. Subsequently, the multilayered cells express Osterix and Type I collagen α, resulting in generation of mature osteoblasts. Therefore, our results indicate that Runx2 is weakly expressed in the LepR+ population without osteoblastic commitment, and the LepR+Runx2-GFPlow stromal cells sit atop the BM stromal hierarchy.
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- 2017
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5. Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis.
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Yuki Ozaki, Masanori Koide, Yuriko Furuya, Tadashi Ninomiya, Hisataka Yasuda, Midori Nakamura, Yasuhiro Kobayashi, Naoyuki Takahashi, Nobuo Yoshinari, and Nobuyuki Udagawa
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Medicine ,Science - Abstract
Osteoblasts express two key molecules for osteoclast differentiation, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), a soluble decoy receptor for RANKL. RANKL induces osteoclastogenesis, while OPG inhibits it by blocking the binding of RANKL to RANK, a cellular receptor of RANKL. OPG-deficient (OPG-/-) mice exhibit severe alveolar bone loss with enhanced bone resorption. WP9QY (W9) peptide binds to RANKL and blocks RANKL-induced osteoclastogenesis. W9 is also reported to stimulate bone formation in vivo. Here, we show that treatment with W9 restores alveolar bone loss in OPG-/-mice by suppressing osteoclastogenesis and enhancing osteoblastogenesis. Administration of W9 or risedronate, a bisphosphonate, to OPG-/-mice significantly decreased the osteoclast number in the alveolar bone. Interestingly, treatment with W9, but not risedronate, enhanced Wnt/β-catenin signaling and induced alveolar bone formation in OPG-/-mice. Expression of sclerostin, an inhibitor of Wnt/β-catenin signaling, was significantly lower in tibiae of OPG-/-mice than in wild-type mice. Treatment with risedronate recovered sclerostin expression in OPG-/-mice, while W9 treatment further suppressed sclerostin expression. Histomorphometric analysis confirmed that bone formation-related parameters in OPG-/-mice, such as osteoblast number, osteoblast surface and osteoid surface, were increased by W9 administration but not by risedronate administration. These results suggest that treatment of OPG-/-mice with W9 suppressed osteoclastogenesis by inhibiting RANKL signaling and enhanced osteoblastogenesis by attenuating sclerostin expression in the alveolar bone. Taken together, W9 may be a useful drug to prevent alveolar bone loss in periodontitis.
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- 2017
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6. A Jak1/2 inhibitor, baricitinib, inhibits osteoclastogenesis by suppressing RANKL expression in osteoblasts in vitro.
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Kohei Murakami, Yasuhiro Kobayashi, Shunsuke Uehara, Takako Suzuki, Masanori Koide, Teruhito Yamashita, Midori Nakamura, Naoyuki Takahashi, Hiroyuki Kato, Nobuyuki Udagawa, and Yukio Nakamura
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Medicine ,Science - Abstract
The Janus kinases (Jaks) are hubs in the signaling process of more than 50 cytokine or hormone receptors. However, the function of Jak in bone metabolism remains to be elucidated. Here, we showed that the inhibition of Jak1 and/or Jak2 in osteoblast-lineage cells led to impaired osteoclastogenesis due to the reduced expression of receptor activator of nuclear factor-κB ligand (RANKL). Murine calvaria-derived osteoblasts induced differentiation of bone marrow cells into osteoclasts in the presence of 1,25-dihydroxyvitamin D3 (1,25D3) and prostaglandin E2 (PGE2) in vitro. However, treatment with the Jak1/2 inhibitor, baricitinib, markedly inhibited osteoclastogenesis in the co-culture. On the other hand, baricitinib did not inhibit RANKL-induced osteoclast differentiation of bone marrow macrophages. These results indicated that baricitinib acted on osteoblasts, but not on bone marrow macrophages. Baricitinib suppressed 1,25D3 and PGE2-induced up-regulation of RANKL in osteoblasts, but not macrophage colony-stimulating factor expression. Moreover, the addition of recombinant RANKL to co-cultures completely rescued baricitinib-induced impairment of osteoclastogenesis. shRNA-mediated knockdown of Jak1 or Jak2 also suppressed RANKL expression in osteoblasts and inhibited osteoclastogenesis. Finally, cytokine array revealed that 1,25D3 and PGE2 stimulated secretion of interleukin-6 (IL-6), IL-11, and leukemia inhibitory factor in the co-culture. Hence, Jak1 and Jak2 represent novel therapeutic targets for osteoporosis as well as inflammatory bone diseases including rheumatoid arthritis.
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- 2017
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7. Roles of Wnt signaling in bone formation and resorption
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Yasuhiro Kobayashi, Kazuhiro Maeda, and Naoyuki Takahashi
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Wnt ,LRP ,Osteoblasts ,Osteoclasts ,β-catenin ,Bone ,Dentistry ,RK1-715 - Abstract
Wnt proteins (Wnts) are palmitoylated and glycosylated ligands that play a central role in the early development of organs and tissues. The discovery that loss-of-function mutations in low density lipoprotein receptor-related protein 5 (LRP5), a Wnt co-receptor, led to low bone mass in humans revealed the possible role of Wnt signaling in the regulation of bone remodeling. Many findings obtained from detailed analyses of mice having mutations of Wnt signaling molecules have confirmed that Wnt signaling has potential roles in bone remodeling in both physiological and pathological conditions. There are two pathways of Wnt signaling: β-catenin-dependent canonical and -independent non-canonical pathways. Wnts act on osteoblast precursor cells and promote their differentiation into mature osteoblasts through the β-catenin-dependent canonical pathway. In addition, Wnts suppress bone resorption by regulating the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) ratio through the same pathway in mature osteoblasts. In contrast, recent studies have shown that the activation of the β-catenin-independent non-canonical pathway enhances the RANKL-induced osteoclast formation in mouse macrophage cultures. These results indicate that Wnt-mediated signals are involved in several aspects of bone formation and bone resorption. This review will summarize the current knowledge of the roles of Wnt signaling in bone formation and resorption.
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- 2008
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8. Long-term Prognosis for Non-ischemic Heart Disease Patients with Premature Ventricular Contraction and Non-sustained Ventricular Tachycardia
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Masakazu Komoriya, MD, Shinobu Imai, MD, Hiroshi Aoyama, MD, Hideki Yagi, MD, Masaaki Nagashima, MD, Mitsunobu Enomoto, MD, Kazutaka Suzuki, MD, Satoshi Yamaji, MD, Hidehito Takase, MD, Kagari Matsudaira, MD, Naoyuki Takahashi, MD, Fumio Saito, MD, Hiroshi Yagi, MD, Toshio Kushiro, MD, Ken Nagao, MD, and Atsushi Hirayama, MD
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Premature ventricular contraction ,Non-ischemic heart disease ,Cardiac function ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
There are few long-term reports of patients with frequent PVCs in the absence of ischemic heart disease. In 86 patients without ischemic heart disease, who had 1000 or more PVCs in 24-hour Holter ECG, the number of PVCs during 24-hours Holter ECG and echocardiographic parameters were followed at least 1 year (66.5 ± 39.7 months). PVC was significantly reduced in the patients with or without underlying diseases (UD). The reduction rate in the number of PVCs was prominent in patients with UD. PVC was significantly reduced in patients under medication, but not in patients without medication. In the comparison between the initial and follow up observation using Wilcoxon's rank test, the number of PVC was significantly reduced (P < 0.05), and EF was also improved (P < 0.05) in angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) group, and in β-blocker group. In Ca-antagonist group and antiarrhythmic drug group, the number of PVCs was also significantly reduced (P < 0.05). Multivariate analysis revealed significantly higher incidence (60% or more with PVC reduction) in ACEI/ARB group. These results suggest that the administration of ACEI/ARB may contribute to the reduction of PVC in non-ischemic heart disease cases with multiple PVC.
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- 2008
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9. Arctigenin inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways.
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Teruhito Yamashita, Shunsuke Uehara, Nobuyuki Udagawa, Feng Li, Shigetoshi Kadota, Hiroyasu Esumi, Yasuhiro Kobayashi, and Naoyuki Takahashi
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Medicine ,Science - Abstract
Arctigenin, a lignan-derived compound, is a constituent of the seeds of Arctium lappa. Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. Here, we showed that arctigenin inhibited the action of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key transcription factor for osteoclastogenesis. NFATc1 in osteoclast precursors was activated through two distinct pathways: the calcineurin-dependent and osteoblastic cell-dependent pathways. Among the several lignan-derived compounds examined, arctigenin most strongly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast-like cell formation in mouse bone marrow macrophage (BMM) cultures, in which the calcineurin-dependent NFATc1 pathway was activated. Arctigenin suppressed neither the activation of nuclear factor κB and mitogen-activated protein kinases nor the up-regulation of c-Fos expression in BMMs treated with RANKL. However, arctigenin suppressed RANKL-induced NFATc1 expression. Interestingly, the treatment of osteoclast-like cells with arctigenin converted NFATc1 into a lower molecular weight species, which was translocated into the nucleus even in the absence of RANKL. Nevertheless, arctigenin as well as cyclosporin A (CsA), a calcineurin inhibitor, suppressed the NFAT-luciferase reporter activity induced by ionomycin and phorbol 12-myristate 13-acetate in BMMs. Chromatin immunoprecipitation analysis confirmed that arctigenin inhibited the recruitment of NFATc1 to the promoter region of the NFATc1 target gene. Arctigenin, but not CsA suppressed osteoclast-like cell formation in co-cultures of osteoblastic cells and bone marrow cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. The forced expression of constitutively active NFATc1 rescued osteoclastogenesis in BMM cultures treated with CsA, but not that treated with arctigenin. Arctigenin also suppressed the pit-forming activity of osteoclast-like cells cultured on dentin slices. These results suggest that arctigenin induces a dominant negative species of NFATc1, which inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways.
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- 2014
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10. c-Fms signaling mediates neurofibromatosis Type-1 osteoclast gain-in-functions.
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Yongzheng He, Steven D Rhodes, Shi Chen, Xiaohua Wu, Jin Yuan, Xianlin Yang, Li Jiang, Xianqi Li, Naoyuki Takahashi, Mingjiang Xu, Khalid S Mohammad, Theresa A Guise, and Feng-Chun Yang
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Medicine ,Science - Abstract
Skeletal abnormalities including osteoporosis and osteopenia occur frequently in both pediatric and adult neurofibromatosis type 1 (NF1) patients. NF1 (Nf1) haploinsufficient osteoclasts and osteoclast progenitors derived from both NF1 patients and Nf1(+/-) mice exhibit increased differentiation, migration, and bone resorptive capacity in vitro, mediated by hyperactivation of p21(Ras) in response to limiting concentrations of macrophage-colony stimulating factor (M-CSF). Here, we show that M-CSF binding to its receptor, c-Fms, results in increased c-Fms activation in Nf1(+/) (-) osteoclast progenitors, mediating multiple gain-in-functions through the downstream effectors Erk1/2 and p90RSK. PLX3397, a potent and selective c-Fms inhibitor, attenuated M-CSF mediated Nf1(+/-) osteoclast migration by 50%, adhesion by 70%, and pit formation by 60%. In vivo, we administered PLX3397 to Nf1(+/-) osteoporotic mice induced by ovariectomy (OVX) and evaluated changes in bone mass and skeletal architecture. We found that PLX3397 prevented bone loss in Nf1(+/-)-OVX mice by reducing osteoclast differentiation and bone resorptive activity in vivo. Collectively, these results implicate the M-CSF/c-Fms signaling axis as a critical pathway underlying the aberrant functioning of Nf1 haploinsufficient osteoclasts and may provide a potential therapeutic target for treating NF1 associated osteoporosis and osteopenia.
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- 2012
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11. Smart management system of customer's battery and heat pump water heater, considering the Japanese new rule for curtailment of PV output.
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Eitaro Omine, Hiroyuki Hatta, Naoyuki Takahashi, and Tsuyoshi Ueno
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- 2017
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12. Design, Synthesis, and Monoamine Oxidase B Selective Inhibitory Activity of N-Arylated Heliamine Analogues
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Makito Yamada, Yu Hirose, Bangzhong Lin, Megumi Fumimoto, Kazuto Nunomura, Sirimangkalakitti Natchanun, Naoyuki Takahashi, Yuuta Ohki, Makoto Sako, Kenichi Murai, Kazuo Harada, Masayoshi Arai, Sayo Suzuki, Tomonori Nakamura, Junichi Haruta, and Mitsuhiro Arisawa
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Organic Chemistry ,Drug Discovery ,Biochemistry - Published
- 2022
13. Myeloid immune checkpoint ILT3/LILRB4/gp49B can co-tether fibronectin with integrin on macrophages
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So Itoi, Naoyuki Takahashi, Haruka Saito, Yusuke Miyata, Mei-Tzu Su, Dai Kezuka, Fumika Itagaki, Shota Endo, Hiroshi Fujii, Hideo Harigae, Yuzuru Sakamoto, and Toshiyuki Takai
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Integrins ,Mice ,Membrane Glycoproteins ,Macrophages ,Immunology ,Cell Adhesion ,Animals ,Humans ,Immunology and Allergy ,General Medicine ,Phosphorylation ,Receptors, Immunologic ,Fibronectins - Abstract
LILRB4 (B4, also known as ILT3/CD85k) is an immune checkpoint of myeloid lineage cells, albeit its mode of function remains obscure. Our recent identification of a common ligand for both human B4 and its murine ortholog gp49B as the fibronectin (FN) N-terminal 30 kDa domain poses the question of how B4/gp49B regulate cellular activity upon recognition of FN in the plasma and/or the extracellular matrix. Since FN in the extracellular matrix is tethered by FN-binding integrins, we hypothesized that B4/gp49B would tether FN in cooperation with integrins on the cell surface, thus they should be in close vicinity to integrins spatially. This scenario suggests a mode of function of B4/gp49B by which the FN-induced signal is regulated. The FN pull-down complex was found to contain gp49B and integrin β 1 in bone marrow-derived macrophages. The confocal fluorescent signals of the three molecules on the intrinsically FN-tethering macrophages were correlated to each other. When FN-poor macrophages adhered to culture plates, the gp49–integrin β 1 signal correlation increased at the focal adhesion, supporting the notion that gp49B and integrin β 1 become spatially closer to each other there. Adherence of RAW264.7 and THP-1 cells to immobilized FN induced phosphorylation of spleen tyrosine kinase, whose level was augmented under B4/gp49B deficiency. Thus, we concluded that B4/gp49B can co-tether FN in cooperation with integrin in the cis configuration on the same cell, forming a B4/gp49B–FN–integrin triplet as a regulatory unit of a focal adhesion-dependent pro-inflammatory signal in macrophages.
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- 2022
14. Dynamic voltage control method and optimization for LVR in distribution system with PV systems.
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Naoyuki Takahashi, Hiroshi Kikusato, Jun Yoshinaga, Yasuhiro Hayashi, Shinichi Kusagawa, and Noriyuki Motegi
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- 2014
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15. Method for determining line drop compensator parameters of low voltage regulator using support vector machine.
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Hiroshi Kikusato, Naoyuki Takahashi, Jun Yoshinaga, Yu Fujimoto, Yasuhiro Hayashi, Shinichi Kusagawa, and Noriyuki Motegi
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- 2014
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16. Co-localization of Fibronectin Receptors LILRB4/gp49B and Integrin on Dendritic Cell Surface
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Naoyuki, Takahashi, So, Itoi, Mei-Tzu, Su, Shota, Endo, and Toshiyuki, Takai
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Integrins ,Membrane Glycoproteins ,Dendritic Cells ,General Medicine ,Ligands ,General Biochemistry, Genetics and Molecular Biology ,Fibronectins ,Mice ,Receptors, Fibronectin ,Focal Adhesion Protein-Tyrosine Kinases ,Cell Adhesion ,Animals ,Humans ,Phosphorylation ,Receptors, Immunologic - Abstract
A myeloid immune checkpoint, leukocyte immunoglobulin-like receptor (LILR) B4 (B4, also known as ILT3/CD85k in humans and gp49B in mice) is expressed on dendritic cells (DCs). However, a mode of regulation of DCs by B4/gp49B is not identified yet in relation to the ligand(s) as well as to the counteracting, activation-type receptor. Our recent identification of the physiological/pathological ligand for B4/gp49B as the fibronectin (FN) N-terminal 30-kDa domain poses the question of the relationship between B4/gp49B and a classical FN receptor/cellular activator, integrin, on DCs. Here we showed that FN is not constitutively tethered on the surface of bone marrow-derived cultured DCs (BMDCs) or splenic DCs, even though the FN receptor integrin and gp49B are co-expressed on these cells. Confocal laser scanning microscopic analysis, however, revealed weak correlation of fluorescent signals between gp49B and integrin β
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- 2022
17. Centralized voltage control method using plural D-STATCOM with controllable dead band in distribution system with renewable energy.
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Naoyuki Takahashi and Yasuhiro Hayashi
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- 2012
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18. Online monitoring and scheduling methods for event-varying DESs with capacity constraints.
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Hiroyuki Goto, Naoyuki Takahashi, Munenori Kasahara, and Yusuke Hasegawa
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- 2007
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19. Product selective reaction controlled by the combination of palladium nanoparticles, continuous microwave irradiation, and a co-existing solid; ligand-free Buchwald–Hartwig amination vs. aryne amination
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Yuuta Ohki, Makito Yamada, Yosuke Murakami, Ryousuke Ohta, Mitsuhiro Arisawa, Kazuo Harada, Toshiki Akiyama, Takeyuki Suzuki, Naoyuki Takahashi, Makoto Sako, Masayoshi Arai, Natchanun Sirimangkalakitti, Hitoshi Haneoka, Tsunayoshi Takehara, and Kenichi Murai
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Chemistry ,Ligand ,Environmental Chemistry ,Nanoparticle ,Leaching (metallurgy) ,Buchwald–Hartwig amination ,Selectivity ,Pollution ,Combinatorial chemistry ,Aryne ,Amination ,Catalysis - Abstract
We have developed a continuous microwave irradiation-assisted Buchwald–Hartwig amination using our original Pd nanoparticle catalyst with a copper plate as a co-existing metal solid. In this methodology, a microwave-controlled product selectivity was achieved between Buchwald–Hartwig amination and aryne amination performed under strongly basic conditions and at a high reaction temperature, because a polar chemical species such as Ar–Pd–halogen might be activated selectively by microwave radiation. Moreover, our catalyst could be used repeatedly over 10 times, and the amount of Pd leaching could be suppressed to a low level.
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- 2021
20. P21-activated kinase regulates oxygen-dependent migration of vascular endothelial cells in monolayers
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Naoyuki Takahashi, Satomi Hirose, Yugo Tabata, Kazuki Sone, Kenichi Funamoto, and Daisuke Yoshino
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Angiogenesis ,media_common.quotation_subject ,p21-activated kinase ,Umbilical vein ,Cellular and Molecular Neuroscience ,medicine ,Human Umbilical Vein Endothelial Cells ,Humans ,microfluidic device ,Internalization ,media_common ,collective cell migration ,Neovascularization, Pathologic ,QH573-671 ,Chemistry ,Kinase ,hypoxia ,vascular endothelial monolayer ,Cell Biology ,Hypoxia (medical) ,Cell biology ,Oxygen tension ,Oxygen ,p21-Activated Kinases ,Limiting oxygen concentration ,medicine.symptom ,Cytology ,Homeostasis ,Research Article ,Research Paper - Abstract
The collective migration of vascular endothelial cells plays important roles in homeostasis and angiogenesis. Oxygen concentration in vivo, which is lower than in the atmosphere and changes due to diseases, is a key factor affecting the cellular dynamics of vascular endothelial cells. We previously reported that hypoxic conditions promote the internalization of vascular endothelial (VE)-cadherin, a specific cell-cell adhesion molecule, and increase the velocity of the collective migration of vascular endothelial cells. However, the mechanism through which cells regulate collective migration as affected by oxygen tension is not fully understood. Here, we investigated oxygen-dependent collective migration, focusing on intracellular protein p21-activated kinase (PAK) and hypoxia-inducing factor (HIF)-1α. A monolayer of human umbilical vein vascular endothelial cells (HUVECs) was formed in a microfluidic device with controllability of oxygen tension. The HUVECs were then exposed to various oxygen conditions in a range from 0.8% to 21% O2, with or without PAK inhibition or chemical stabilization of HIF-1α. Collective cell migration was measured by particle image velocimetry with time-lapse phase-contrast microscopic images. Localizations of VE-cadherin and HIF-1α were quantified by immunofluorescent staining. The collective migration of HUVECs varied in an oxygen-dependent fashion; the migration speed was increased by hypoxic exposure down to 1% O2, while it decreased under an extremely low oxygen tension of less than 1% O2. PAK inhibition suppressed the hypoxia-induced increase of the migration speed by preventing VE-cadherin internalization into HUVECs. A decrease in the migration speed was also obtained by chemical stabilization of HIF-1α, suggesting that excessive accumulation of HIF-1α diminishes collective cell migration. These results indicate that the oxygen-dependent variation of the migration speed of vascular endothelial cells is mediated by the regulation of VE-cadherin through the PAK pathway, as well as other mechanisms via HIF-1α, especially under extreme hypoxic conditions.
- Published
- 2021
21. Development of data extraction method based on clustering method and CVI
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Naoyuki Takahashi
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General Medicine - Published
- 2020
22. Parathyroid Hormone Shifts Cell Fate of a Leptin Receptor‐Marked Stromal Population from Adipogenic to Osteoblastic Lineage
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Yasuhiro Kobayashi, Koichi Matsuo, Naoyuki Takahashi, Toru Hiraga, Ryoko Takao-Kawabata, Nobuyuki Udagawa, Atsushi Arai, Akira Yamaguchi, Toshinori Ishizuya, Toshihisa Komori, Mengyu Yang, Yukihiro Isogai, Kohei Murakami, Toshihide Mizoguchi, Lijuan Zhao, and Daisuke Nishida
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musculoskeletal diseases ,0301 basic medicine ,endocrine system ,medicine.medical_specialty ,Stromal cell ,Endocrinology, Diabetes and Metabolism ,Population ,Parathyroid hormone ,Mice, Transgenic ,030209 endocrinology & metabolism ,Bone tissue ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Orthopedics and Sports Medicine ,education ,education.field_of_study ,Adipogenesis ,Osteoblasts ,Leptin receptor ,Chemistry ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,Osteoblast ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Parathyroid Hormone ,Receptors, Leptin ,Female ,hormones, hormone substitutes, and hormone antagonists - Abstract
Intermittent parathyroid hormone (iPTH) treatment induces bone anabolic effects that result in the recovery of osteoporotic bone loss. Human PTH is usually given to osteoporotic patients because it induces osteoblastogenesis. However, the mechanism by which PTH stimulates the expansion of stromal cell populations and their maturation toward the osteoblastic cell lineage has not be elucidated. Mouse genetic lineage tracing revealed that iPTH treatment induced osteoblastic differentiation of bone marrow (BM) mesenchymal stem and progenitor cells (MSPCs), which carried the leptin receptor (LepR)-Cre. Although these findings suggested that part of the PTH-induced bone anabolic action is exerted because of osteoblastic commitment of MSPCs, little is known about the in vivo mechanistic details of these processes. Here, we showed that LepR+ MSPCs differentiated into type I collagen (Col1)+ mature osteoblasts in response to iPTH treatment. Along with osteoblastogenesis, the number of Col1+ mature osteoblasts increased around the bone surface, although most of them were characterized as quiescent cells. However, the number of LepR-Cre-marked lineage cells in a proliferative state also increased in the vicinity of bone tissue after iPTH treatment. The expression levels of SP7/osterix (Osx) and Col1, which are markers for osteoblasts, were also increased in the LepR+ MSPCs population in response to iPTH treatment. In contrast, the expression levels of Cebpb, Pparg, and Zfp467, which are adipocyte markers, decreased in this population. Consistent with these results, iPTH treatment inhibited 5-fluorouracil- or ovariectomy (OVX)-induced LepR+ MSPC-derived adipogenesis in BM and increased LepR+ MSPC-derived osteoblasts, even under the adipocyte-induced conditions. Treatment of OVX rats with iPTH significantly affected the osteoporotic bone tissue and expansion of the BM adipose tissue. These results indicated that iPTH treatment induced transient proliferation of the LepR+ MSPCs and skewed their lineage differentiation from adipocytes toward osteoblasts, resulting in an expanded, quiescent, and mature osteoblast population. © 2019 American Society for Bone and Mineral Research.
- Published
- 2019
23. Murine osteoclasts secrete serine protease HtrA1 capable of degrading osteoprotegerin in the bone microenvironment
- Author
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Hitoshi Ogata, Yuki Yonemoto, Naoyuki Takahashi, Takahiro Ichihara, Nagahiro Ochiai, Nobuyuki Udagawa, Natsuko Fujimoto, Tatsuo Suda, Tomotaka Yokoo, Yasuhiro Kobayashi, Yasushi Okazaki, Takehiko Kato, Yutaka Nakachi, Tore Eriksson, Shinsuke Kaku, and Tomokazu Ueki
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musculoskeletal diseases ,Cellular differentiation ,Osteoclasts ,Medicine (miscellaneous) ,Bone Marrow Cells ,Bone and Bones ,Article ,General Biochemistry, Genetics and Molecular Biology ,Bone resorption ,Mice ,Multinucleate ,Osteoprotegerin ,Osteogenesis ,Animals ,Receptor ,lcsh:QH301-705.5 ,Cells, Cultured ,Osteoblasts ,biology ,Sequence Analysis, RNA ,Chemistry ,Activator (genetics) ,Macrophages ,Cell Differentiation ,Serine Protease HTRA1 ,High-Temperature Requirement A Serine Peptidase 1 ,eye diseases ,Cell biology ,Cellular Microenvironment ,Matrix Metalloproteinase 9 ,lcsh:Biology (General) ,RANKL ,Proteolysis ,biology.protein ,General Agricultural and Biological Sciences - Abstract
Osteoclasts are multinucleated cells responsible for bone resorption. The differentiation of osteoclasts from bone marrow macrophages (BMMs) is induced by receptor activator of NF-κB ligand (RANKL). Osteoprotegerin (OPG), a decoy receptor of RANKL, inhibits osteoclastogenesis by blocking RANKL signaling. Here we investigated the degradation of OPG in vitro. Osteoclasts, but not BMMs, secreted OPG-degrading enzymes. Using mass spectrometry and RNA-sequencing analysis, we identified high-temperature requirement A serine peptidase 1 (HtrA1) as an OPG-degrading enzyme. HtrA1 did not degrade OPG pre-reduced by dithiothreitol, suggesting that HtrA1 recognizes the three-dimensional structure of OPG. HtrA1 initially cleaved the amide bond between leucine 90 and glutamine 91 of OPG, then degraded OPG into small fragments. Inhibitory activity of OPG on RANKL-induced osteoclastogenesis was suppressed by adding HtrA1 in RAW 264.7 cell cultures. These results suggest that osteoclasts potentially prepare a microenvironment suitable for osteoclastogenesis. HtrA1 may be a novel drug target for osteoporosis., Nagahiro Ochiai et al. report that osteoclasts, but not bone marrow macrophages, secrete a serine protease HtrA1 that can degrade osteoprotegerin in the bone microenvironment. Their results suggest HtrA1 recognizes the three-dimensional structure of osteoprotegerin and may function to prepare the microenvironment for osteoclastogenesis.
- Published
- 2019
24. Ligand-free Suzuki–Miyaura coupling reaction of an aryl chloride using a continuous irradiation type microwave and a palladium nanoparticle catalyst: effect of a co-existing solid
- Author
-
Toshiki Akiyama, Makito Yamada, Yuuta Ohki, Tetsuo Honma, Yasunori Shio, Naoyuki Takahashi, Kenichi Murai, and Mitsuhiro Arisawa
- Subjects
010405 organic chemistry ,Ligand ,Aryl ,chemistry.chemical_element ,Nanoparticle ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Pollution ,Chloride ,Coupling reaction ,0104 chemical sciences ,Catalysis ,Metal ,chemistry.chemical_compound ,chemistry ,visual_art ,medicine ,visual_art.visual_art_medium ,Environmental Chemistry ,medicine.drug ,Palladium - Abstract
We have explored the effect of a co-existing metal in the ligand-free Suzuki–Miyaura coupling reaction of an aryl chloride, which is promoted by a “continuous irradiation type microwave” and a “palladium nanoparticle catalyst”, and found that the co-existing metal affects this reaction due to its absorption ability of microwave energy in the reaction system. We also observed that spiking occurred more frequently in the presence of a co-existing metal.
- Published
- 2019
25. Method for the voltage estimation in large-scale distributed generators under power fluctuations
- Author
-
Satoshi Uemura, Naoyuki Takahashi, and Haruki Oue
- Subjects
Distribution system ,Distribution (number theory) ,Scale (ratio) ,Control theory ,Computer science ,Phase (waves) ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect ,Line (electrical engineering) ,Voltage drop ,Power (physics) ,Voltage - Abstract
The use of grid-connected distributed generators (DGs) is increasing rapidly in Japan. In the distribution system with large-scale DG installations, the reverse power flow from DGs leads to a decrease in the line voltage due to the changes in the voltage phase; this is not well-known as the voltage drop phenomenon. As a result, it is difficult to estimate distribution voltages with the conventional voltage-estimation method based on only the measured information when the power flow in the distribution system is different from the measured voltage. To address the estimation problem, in this paper, we propose a simple voltage-estimation method that integrates the facility information about the medium-voltage power distribution system with the measured information. Numerical simulations have been performed to validate this method using the distribution system model and the conventional voltage estimation model. The proposed method achieves a voltage estimation with higher accuracy as compared to that estimated by the conventional method.
- Published
- 2020
26. The Vitamin D Receptor in Osteoblast-Lineage Cells Is Essential for the Proresorptive Activity of 1α,25(OH)2D3 In Vivo
- Author
-
Nobuyuki Udagawa, Yoko Yamamoto, Hisataka Yasuda, Tomoki Mori, Masanori Koide, Kanji Horibe, Yuko Nakamichi, Naoyuki Takahashi, Shigeaki Kato, and Shunsuke Uehara
- Subjects
Male ,musculoskeletal diseases ,0301 basic medicine ,medicine.medical_specialty ,Proresorptive action ,Mice, Obese ,chemistry.chemical_element ,Mice, Transgenic ,030209 endocrinology & metabolism ,Calcium ,toxic action ,Calcitriol receptor ,Bone and Bones ,Bone resorption ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,N-terminal telopeptide ,Osteoclast ,osteoblast-lineage cells ,Internal medicine ,medicine ,Animals ,Cell Lineage ,Obesity ,Bone Resorption ,Vitamin D ,Research Articles ,VDR ,Osteoblasts ,biology ,hypercalcemia ,Eldecalcitol ,Ob-VDR-cKO mice ,Mice, Inbred C57BL ,Fibroblast Growth Factor-23 ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,RANKL ,biology.protein ,Receptors, Calcitriol ,Female ,AcademicSubjects/MED00250 ,Type I collagen - Abstract
We previously reported that daily administration of a pharmacological dose of eldecalcitol, an analog of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], increased bone mass by suppressing bone resorption. These antiresorptive effects were found to be mediated by the vitamin D receptor (VDR) in osteoblast-lineage cells. Using osteoblast-lineage-specific VDR conditional knockout (Ob-VDR-cKO) mice, we examined whether proresorptive activity induced by the high-dose 1α,25(OH)2D3 was also mediated by VDR in osteoblast-lineage cells. Administration of 1α,25(OH)2D3 (5 μg/kg body weight/day) to wild-type mice for 4 days increased the number of osteoclasts in bone and serum concentrations of C-terminal crosslinked telopeptide of type I collagen (CTX-I, a bone resorption marker). The stimulation of bone resorption was concomitant with the increase in serum calcium (Ca) and fibroblast growth factor 23 (FGF23) levels, and decrease in body weight. This suggests that a toxic dose of 1α,25(OH)2D3 can induce bone resorption and hypercalcemia. In contrast, pretreatment of wild-type mice with neutralizing anti-receptor activator of NF-κB ligand (RANKL) antibody inhibited the 1α,25(OH)2D3-induced increase of osteoclast numbers in bone, and increase of CTX-I, Ca, and FGF23 levels in serum. The pretreatment with anti-RANKL antibody also inhibited the 1α,25(OH)2D3-induced decrease in body weight. Consistent with observations in mice conditioned with anti-RANKL antibody, the high-dose administration of 1α,25(OH)2D3 to Ob-VDR-cKO mice failed to significantly increase bone osteoclast numbers, serum CTX-I, Ca, or FGF23 levels, and failed to reduce the body weight. Taken together, this study demonstrated that the proresorptive, hypercalcemic, and toxic actions of high-dose 1α,25(OH)2D3 are mediated by VDR in osteoblast-lineage cells.
- Published
- 2020
27. Sclerostin expression in trabecular bone is downregulated by osteoclasts
- Author
-
Teruhito Yamashita, Kohei Murakami, Naoyuki Takahashi, Masanori Koide, Keigo Nakamura, Midori Nakamura, Hisataka Yasuda, Mai Matsushita, Nobuyuki Udagawa, Yasuhiro Kobayashi, Josef M. Penninger, Shunsuke Uehara, and Toshiaki Ara
- Subjects
0301 basic medicine ,Male ,Bone density ,lcsh:Medicine ,Osteoclasts ,Leukemia Inhibitory Factor ,Biochemistry ,Bone remodeling ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Bone Density ,Genetics research ,lcsh:Science ,Wnt Signaling Pathway ,Multidisciplinary ,biology ,Chemistry ,Immunochemistry ,Wnt signaling pathway ,Up-Regulation ,Experimental models of disease ,medicine.anatomical_structure ,Calcium and phosphate metabolic disorders ,RANKL ,Cancellous Bone ,Bone Remodeling ,musculoskeletal diseases ,medicine.medical_specialty ,Cell biology ,Drug development ,Antibodies ,Article ,03 medical and health sciences ,Downregulation and upregulation ,Internal medicine ,medicine ,Biomarkers, Tumor ,Cortical Bone ,Animals ,Adaptor Proteins, Signal Transducing ,lcsh:R ,RANK Ligand ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,biology.protein ,Sclerostin ,lcsh:Q ,Cortical bone ,Leukemia inhibitory factor ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Bone tissues have trabecular bone with a high bone turnover and cortical bone with a low turnover. The mechanisms by which the turnover rate of these bone tissues is determined remain unclear. Osteocytes secrete sclerostin, a Wnt/β-catenin signaling antagonist, and inhibit bone formation. We found that sclerostin expression in cortical bone is more marked than in trabecular bone in Sost reporter mice. Leukemia inhibitory factor (LIF) secreted from osteoclasts reportedly suppressed sclerostin expression and promoted bone formation. Here, we report that osteoclasts downregulate sclerostin expression in trabecular bone and promote bone turnover. Treatment of C57BL/6 mice with an anti-RANKL antibody eliminated the number of osteoclasts and LIF-positive cells in trabecular bone. The number of sclerostin-positive cells was increased in trabecular bone, while the number of β-catenin-positive cells and bone formation were decreased in trabecular bone. Besides, Tnfsf11 heterozygous (Rankl+/−) mice exhibited a decreased number of LIF-positive cells and increased number of sclerostin-positive cells in trabecular bone. Rankl+/− mice exhibited a decreased number of β-catenin-positive cells and reduced bone formation in trabecular bone. Furthermore, in cultured osteoclasts, RANKL stimulation increased Lif mRNA expression, suggesting that RANKL signal increased LIF expression. In conclusion, osteoclasts downregulate sclerostin expression and promote trabecular bone turnover.
- Published
- 2020
28. List of Contributors
- Author
-
David Abraham, Maria Almeida, Elena Ambrogini, Andrew Arnold, Bence Bakos, Clemens Bergwitz, Daniel D. Bikle, John P. Bilezikian, Neil Binkley, Alessandro Bisello, L.F. Bonewald, George Bou-Gharios, Roger Bouillon, Mary L. Bouxsein, Brendan F. Boyce, Steven Boyd, Maria Luisa Brandi, David B. Burr, Laura M. Calvi, Ernesto Canalis, Xu Cao, Geert Carmeliet, Thomas O. Carpenter, Wenhan Chang, Shek Man Chim, Shilpa Choudhary, Sylvia Christakos, Yong-Hee Patricia Chun, Cristiana Cipriani, Roberto Civitelli, Thomas L. Clemens, Michael T. Collins, Caterina Conte, Mark S. Cooper, Jillian Cornish, Serge Cremers, Bess Dawson-Hughes, Benoit de Crombrugghe, Hector F. DeLuca, David W. Dempster, Matthew T. Drake, Patricia Ducy, Frank H. Ebetino, Klaus Engelke, Reinhold G. Erben, David R. Eyre, Charles R. Farber, Marina Feigenson, Mathieu Ferron, Pablo Florenzano, Francesca Fontana, Brian L. Foster, Peter A. Friedman, Seiji Fukumoto, Laura W. Gamer, Thomas J. Gardella, Patrick Garnero, Harry K. Genant, Francesca Giusti, Andy Göbel, David Goltzman, Jeffrey P. Gorski, James Griffith, R. Graham G Russell, Kurt D. Hankenson, Fadil M. Hannan, Stephen E. Harris, Iris R. Hartley, Christine Hartmann, Robert P. Heaney, Geoffrey N. Hendy, Matthew J. Hilton, Lorenz C. Hofbauer, Gill Holdsworth, Yi-Hsiang Hsu, David M. Hudson, Marja Hurley, Karl L. Insogna, Robert L. Jilka, Mark L. Johnson, Rachelle W. Johnson, Glenville Jones, Stefan Judex, Harald Jüppner, Ivo Kalajzic, Gérard Karsenty, Hua Zhu Ke, Sundeep Khosla, Douglas P. Kiel, J. Klein-Nulend, Frank C. Ko, Yasuhiro Kobayashi, Martin Konrad, Paul J. Kostenuik, Christopher S. Kovacs, Richard Kremer, Venkatesh Krishnan, Henry M. Kronenberg, Peter A. Lakatos, Uri A. Liberman, Joseph A. Lorenzo, Conor C. Lynch, Karen M. Lyons, Y. Linda Ma, Christa Maes, Michael Mannstadt, Stavros Manolagas, Robert Marcus, David E. Maridas, Pierre J. Marie, Francesca Marini, Jasna Markovac, T. John Martin, Brya G. Matthews, Antonio Maurizi, Sasan Mirfakhraee, Sharon M. Moe, David G. Monroe, Carolina A. Moreira, Ralph Müller, David S. Musson, Teruyo Nakatani, Dorit Naot, Nicola Napoli, Tally Naveh-Many, Edward F. Nemeth, Thomas L. Nickolas, Michael S. Ominsky, Noriaki Ono, David M. Ornitz, Nicola C. Partridge, Vihitaben S. Patel, J. Wesley Pike, Carol Pilbeam, Lori Plum, John T. Potts, J. Edward Puzas, Tilman D. Rachner, Audrey Rakian, Rubie Rakian, Nora E. Renthal, Julie A. Rhoades (Sterling), Mara Riminucci, Scott J. Roberts, Pamela Gehron Robey, Michael J. Rogers, G. David Roodman, Clifford J. Rosen, Vicki Rosen, David W. Rowe, Janet Rubin, Clinton T. Rubin, Karl P. Schlingmann, Ego Seeman, Markus J. Seibel, Chris Sempos, Dolores M. Shoback, Caroline Silve, Justin Silver, Natalie A. Sims, Frederick R. Singer, Joseph P. Stains, Steve Stegen, Paula H. Stern, Gaia Tabacco, Istvan Takacs, Naoyuki Takahashi, Donovan Tay, Anna Teti, Rajesh V. Thakker, Ryan E. Tomlinson, Francesco Tonelli, Dwight A. Towler, Elena Tsourdi, Chia-Ling Tu, Nobuyuki Udagawa, Connie M. Weaver, Marc N. Wein, Lee S. Weinstein, MaryAnn Weis, Michael P. Whyte, Bart O. Williams, Xin Xu, Shoshana Yakar, Yingzi Yang, Stefano Zanotti, and Hong Zhou
- Published
- 2020
29. Osteoclasts
- Author
-
Naoyuki Takahashi, Yasuhiro Kobayashi, and Nobuyuki Udagawa
- Published
- 2020
30. Vitamin D in The Regulation of Osteoclasts
- Author
-
Naoyuki Takahashi, Yuko Nakamichi, and Nobuyuki Udagawa
- Published
- 2020
31. Mechanisms involved in bone resorption regulated by vitamin D
- Author
-
Naoyuki Takahashi, Yuko Nakamichi, Tatsuo Suda, and Nobuyuki Udagawa
- Subjects
musculoskeletal diseases ,0301 basic medicine ,Genetically modified mouse ,endocrine system ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Osteoporosis ,030209 endocrinology & metabolism ,Biochemistry ,Calcitriol receptor ,Bone resorption ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Osteogenesis ,Internal medicine ,medicine ,Vitamin D and neurology ,Animals ,Humans ,Bone Resorption ,Vitamin D ,Molecular Biology ,Cathepsin ,Bone mineral ,Receptor Activator of Nuclear Factor-kappa B ,Chemistry ,RANK Ligand ,Osteoprotegerin ,Osteoblast ,Vitamins ,Cell Biology ,medicine.disease ,Fibroblast Growth Factor-23 ,030104 developmental biology ,medicine.anatomical_structure ,Receptors, Calcitriol ,Molecular Medicine - Abstract
Active forms of vitamin D enhance osteoclastogenesis in vitro and in vivo through the vitamin D receptor (VDR) in osteoblast-lineage cells consisting of osteoblasts and osteocytes. This pro-resorptive activity was evident basically with higher concentrations of active vitamin D than those expected in physiological conditions. Nevertheless, vitamin D compounds have been used in Japan for treating osteoporosis to increase bone mineral density (BMD). Of note, the increase in BMD by long-term treatment with pharmacological (=near-physiological) doses of vitamin D compounds was caused by the suppression of bone resorption. Therefore, whether vitamin D expresses pro-resorptive or anti-resorptive properties seems to be dependent on the treatment protocols. We established osteoblast lineage-specific and osteoclast-specific VDR conditional knockout (cKO) mice using Osterix-Cre transgenic mice and Cathepsin K-Cre knock-in mice, respectively. According to our observation using these cKO mouse lines, neither VDR in osteoblast-lineage cells nor that in osteoclasts played important roles for osteoclastogenesis and bone resorption at homeostasis. However, using our cKO lines, we observed that VDR in osteoblast-lineage cells, but not osteoclasts, was involved in the anti-resorptive properties of pharmacological doses of vitamin D compounds in vivo. Two different osteoblast-lineage VDR cKO mouse lines were reported. One is a VDR cKO mouse line using alpha 1, type I collagen (Col1a1)-Cre transgenic mice (here we call Col1a1-VDR-cKO mice) and the other is that using dentin matrix protein 1 (Dmp1)-Cre transgenic mice (Dmp1-VDR-cKO mice). Col1a1-VDR-cKO mice exhibited slightly increased bone mass due to lowered bone resorption. In contrast, Dmp1-VDR-cKO mice exhibited no difference in BMD in agreement with our results regarding Ob-VDR-cKO mice. Here we discuss contradictory results and multiple modes of actions of vitamin D in bone resorption in detail. (279 words).
- Published
- 2018
32. Individual control method for hybrid voltage regulator
- Author
-
Naoyuki Takahashi, Suresh Chand Verma, Yasuyuki Kunii, Hukashi Ueda, Satoshi Uemura, Shunsuke Sasaki, and Morihiro Iwata
- Subjects
Low-dropout regulator ,Dropout voltage ,Control theory ,General Medicine ,Voltage regulator ,Control methods ,Mathematics - Published
- 2017
33. Bone Formation Is Coupled to Resorption Via Suppression of Sclerostin Expression by Osteoclasts
- Author
-
Naoyuki Takahashi, Hisataka Yasuda, Tadahiro Iimura, Yasuhiro Kobayashi, Nobuyuki Udagawa, Yuki Ozaki, Shunsuke Uehara, Midori Nakamura, Masanori Koide, B. Yukihiro Hiraoka, and Teruhito Yamashita
- Subjects
musculoskeletal diseases ,0301 basic medicine ,medicine.medical_specialty ,Chemistry ,Endocrinology, Diabetes and Metabolism ,Wnt signaling pathway ,Bone resorption ,Bone remodeling ,Resorption ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Osteoclast ,Internal medicine ,Osteocyte ,medicine ,Sclerostin ,Orthopedics and Sports Medicine ,Leukemia inhibitory factor - Abstract
Bone formation is coupled to bone resorption throughout life. However, the coupling mechanisms are not fully elucidated. Using Tnfrsf11b-deficient (OPG-/- ) mice, in which bone formation is clearly coupled to bone resorption, we found here that osteoclasts suppress the expression of sclerostin, a Wnt antagonist, thereby promoting bone formation. Wnt/β-catenin signals were higher in OPG-/- and RANKL-transgenic mice with a low level of sclerostin. Conditioned medium from osteoclast cultures (Ocl-CM) suppressed sclerostin expression in UMR106 cells and osteocyte cultures. In vitro experiments revealed that osteoclasts secreted leukemia inhibitory factor (LIF) and inhibited sclerostin expression. Anti-RANKL antibodies, antiresorptive agents, suppressed LIF expression and increased sclerostin expression, thereby reducing bone formation in OPG-/- mice. Taken together, osteoclast-derived LIF regulates bone turnover through sclerostin expression. Thus, LIF represents a target for improving the prolonged suppression of bone turnover by antiresorptive agents. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
- Published
- 2017
34. VDR in Osteoblast-Lineage Cells Primarily Mediates Vitamin D Treatment-Induced Increase in Bone Mass by Suppressing Bone Resorption
- Author
-
Yoko Yamamoto, Tatsuo Suda, Toshihide Mizoguchi, Takashi Nakamura, Shigeaki Kato, Nobuyuki Udagawa, Kanji Horibe, Akihiro Hosoya, Yuko Nakamichi, and Naoyuki Takahashi
- Subjects
musculoskeletal diseases ,0301 basic medicine ,Vitamin ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Calcitriol receptor ,Bone resorption ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,polycyclic compounds ,medicine ,Vitamin D and neurology ,Orthopedics and Sports Medicine ,digestive, oral, and skin physiology ,Osteoblast ,Eldecalcitol ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,lipids (amino acids, peptides, and proteins) ,Secondary osteoporosis ,Hormone - Abstract
Long-term treatment with active vitamin D [1α,25(OH)2D3] and its derivatives is effective for increasing bone mass in patients with primary and secondary osteoporosis. Derivatives of 1α,25(OH)2D3, including eldecalcitol (ELD), exert their actions through the vitamin D receptor (VDR). ELD is more resistant to metabolic degradation than 1α,25(OH)2D3. It is reported that ELD treatment causes a net increase in bone mass by suppressing bone resorption rather than by increasing bone formation in animals and humans. VDR in bone and extraskeletal tissues regulates bone mass and secretion of osteotropic hormones. Therefore, it is unclear what types of cells expressing VDR preferentially regulate the vitamin D–induced increase in bone mass. Here, we examined the effects of 4-week treatment with ELD (50 ng/kg/day) on bone using osteoblast lineage-specific VDR conditional knockout (Ob-VDR-cKO) and osteoclast-specific VDR cKO (Ocl-VDR-cKO) male mice aged 10 weeks. Immunohistochemically, VDR in bone was detected preferentially in osteoblasts and osteocytes. Ob-VDR-cKO mice showed normal bone phenotypes, despite no appreciable immunostaining of VDR in bone. Ob-VDR-cKO mice failed to increase bone mass in response to ELD treatment. Ocl-VDR-cKO mice also exhibited normal bone phenotypes, but normally responded to ELD. ELD-induced FGF23 production in bone was regulated by VDR in osteoblast-lineage cells. These findings suggest that the vitamin D treatment-induced increase in bone mass is mediated by suppressing bone resorption through VDR in osteoblast-lineage cells. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
- Published
- 2017
35. In-line and Real-time Monitoring of Resonant Acoustic Mixing by Near-infrared Spectroscopy Combined with Chemometric Technology for Process Analytical Technology Applications in Pharmaceutical Powder Blending Systems
- Author
-
Kazuhide Ashizawa, Ryoma Tanaka, Yasuaki Nakamura, Makoto Otsuka, Yusuke Hattori, and Naoyuki Takahashi
- Subjects
Informatics ,Time Factors ,Drug Compounding ,Process analytical technology ,02 engineering and technology ,01 natural sciences ,Quality by Design ,Analytical Chemistry ,Chemometrics ,Acceleration ,Partial least squares regression ,Process engineering ,Mixing (physics) ,Spectroscopy, Near-Infrared ,business.industry ,Chemistry ,010401 analytical chemistry ,Near-infrared spectroscopy ,Process (computing) ,Acoustics ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Pharmaceutical Preparations ,Calibration ,Powders ,0210 nano-technology ,business - Abstract
Resonant acoustic® mixing (RAM) technology is a system that performs high-speed mixing by vibration through the control of acceleration and frequency. In recent years, real-time process monitoring and prediction has become of increasing interest, and process analytical technology (PAT) systems will be increasingly introduced into actual manufacturing processes. This study examined the application of PAT with the combination of RAM, near-infrared spectroscopy, and chemometric technology as a set of PAT tools for introduction into actual pharmaceutical powder blending processes. Content uniformity was based on a robust partial least squares regression (PLSR) model constructed to manage the RAM configuration parameters and the changing concentration of the components. As a result, real-time monitoring may be possible and could be successfully demonstrated for in-line real-time prediction of active pharmaceutical ingredients and other additives using chemometric technology. This system is expected to be applicable to the RAM method for the risk management of quality.
- Published
- 2017
36. Ligand-free Suzuki–Miyaura coupling using ruthenium(0) nanoparticles and a continuously irradiating microwave system
- Author
-
Nozomi Saito, Toshiki Akiyama, Ryohei Doi, Mitsuhiro Arisawa, Yoshihiro Sato, Naoyuki Takahashi, Yusuke Tamenori, Yuuta Ohki, Tetsuo Honma, Hiromichi Fujioka, and Takahisa Taniguchi
- Subjects
Materials science ,010405 organic chemistry ,Aryl ,Inorganic chemistry ,Halide ,chemistry.chemical_element ,Nanoparticle ,010402 general chemistry ,01 natural sciences ,Pollution ,Combinatorial chemistry ,0104 chemical sciences ,Catalysis ,Ruthenium ,Metal ,chemistry.chemical_compound ,chemistry ,visual_art ,visual_art.visual_art_medium ,Environmental Chemistry ,Leaching (metallurgy) ,Microwave - Abstract
We developed a conceptually and methodologically novel ruthenium(0) nanoparticle catalyst, sulfur-modified Au-supported ruthenium nanoparticles (SARu). SARu is easily prepared through a three-step procedure involving simultaneous in situ metal nanoparticle and nanospace organization. This unique method does not require any conventional preformed template to immobilize and stabilize metal nanoparticles. SARu is an ideal ruthenium catalyst for liquid-phase combinatorial synthesis because it repeatedly catalyzes ligand-free Suzuki–Miyaura coupling of aryl halides, including aryl chlorides, with arylboronic acids with low Ru leaching. Physical analysis of SARu showed that the active species in these reactions were ruthenium (0) nanoparticles with a size of 1–3 nm. Also, we developed a continuously irradiating microwave methodology, which can first time discriminate the heating effect and the microwave effect in microwave experiments.
- Published
- 2017
37. Advanced Autonomous Voltage-Control Method using Sensor Data in a Distribution Power System
- Author
-
Naoyuki Takahashi
- Subjects
Distribution system ,Distribution power system ,Computer science ,Control theory ,Voltage control ,Server ,Drop (telecommunication) ,Voltage regulator ,Voltage reference ,Voltage - Abstract
PVs have been rapidly incorporated within power distribution systems after the operation of Feed In Tariff (FIT). Step Voltage Regulator (SVR) with Line Drop Compensator method has been installed to the power distribution system to control rising voltages due to the reverse flow from PVs. LDC controls the distribution voltage based on the estimated voltage obtained via sensor measurements in real-time. However, using LDC, it is difficult to maintain the distribution voltage within a specified range because the estimation error expands with increasing PV installed capacity. In Japan, a type of automatic switch with voltage and current sensors (IT-switch) has been installed to detect an accident point in the power distribution system. IT-switching can monitor line voltage and current in each phase, and measured data are transferred to data servers. This paper proposes an advanced, autonomous voltage-control method to improve the estimation accuracy and voltage control performance of SVR, using the reference database to address the voltage deviation problem. The proposed method estimates a voltage width of the control target voltage in real-time as a reference voltage by using the measured (online) data and database (offline) data. To determine the validity of the proposed method, we conducted numerical simulations and compared the voltage control performance and the influence of SVR life span using a model power distribution system. The results indicates that the proposed method improved the voltage control performance and SVR life span by improving the estimation accuracy through the integration of real-time measured data and the reference database.
- Published
- 2019
38. Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6
- Author
-
Tatsuya Tamura, Nobuyuki Udagawa, Naoyuki Takahashi, Chisato Miyaura, Sakae Tanaka, Yoshiki Yamada, Yasuo Koishihara, Yoshiyuki Ohsugi, Kenji Kumaki, Tetsuya Taga, Tadamitsu Kishimoto, and Tatsuo Suda
- Subjects
Interleukin-6 -- Analysis ,Osteoclasis -- Research ,Interleukins -- Structure-activity relationships ,Science and technology - Abstract
Analyses of the function of soluble interleukin (IL)-6 receptor (sIL-6R) in osteoclast formation by IL-6 involved the application a coculture of mouse osteoblasts and bone marrow cells. A process involving 130-kDa glycoprotein chain induces osteoclast formation by enhanced circulation or locally generated sIL-6R in the presence of IL-6.
- Published
- 1993
39. Verification of the mixing processes of the active pharmaceutical ingredient, excipient and lubricant in a pharmaceutical formulation using a resonant acoustic mixing technology
- Author
-
Ryoma Tanaka, Yusuke Hattori, Naoyuki Takahashi, Yasuaki Nakamura, Kazuhide Ashizawa, and Makoto Otsuka
- Subjects
Active ingredient ,Materials science ,General Chemical Engineering ,Analytical chemistry ,Mixing (process engineering) ,Excipient ,02 engineering and technology ,General Chemistry ,Pharmaceutical formulation ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Angle of repose ,0104 chemical sciences ,medicine ,Pharmaceutical manufacturing ,Lubricant ,Composite material ,0210 nano-technology ,Dissolution ,medicine.drug - Abstract
Mixing processes are important for making high-quality pharmaceutical formulations and are related to dissolution and chemical stability in pharmaceutical manufacturing. The resonant acoustic® mixing (RAM) technology is a blending method, and it has been reported that it has a unique mixing action for various samples. In this study, in order to apply the RAM method to the pharmaceutical blending process, optimization of the operating conditions of RAM (acceleration and frequency) was conducted by numerical simulation. Powder mixing experiments were carried out using various RAM conditions and also a modified V-shaped mixing device with a powder material of theophylline powder and lactose or magnesium oxide and lactose. The angle of repose of the mixed powder sample was measured as an index of powder flowability and also the degree of powder mixing. A drug uniformity test of the mixed powders was performed to measure theophylline content using high-performance liquid chromatography. The results of these experiments indicate that the optimum values for acceleration and frequency in RAM mixing are 90–100 G and approximately 60 Hz, respectively, which prove the superiority of the RAM method over the ordinary mixing method. The RAM method was estimated to throw the powder upward into the air and perform mixing by utilizing free-fall, possibly by inducing a weightless state without depending on the density and mass of the sample. Therefore, RAM may be applicable to pharmaceutical manufacturing processes.
- Published
- 2016
40. Basic study on dynamic reactive-power control method with PV output prediction for solar inverter
- Author
-
Ryunosuke Miyoshi, Yasuhiro Hayashi, and Naoyuki Takahashi
- Subjects
PV output prediction ,Engineering ,Solar inverter ,business.industry ,020209 energy ,Photovoltaic system ,02 engineering and technology ,AC power ,Maximum power point tracking ,Reactive-power control ,Control theory ,0202 electrical engineering, electronic engineering, information engineering ,Electronic engineering ,Grid-connected photovoltaic power system ,Waveform ,lcsh:Electrical engineering. Electronics. Nuclear engineering ,business ,lcsh:TK1-9971 ,Voltage ,Power control - Abstract
To effectively utilize a photovoltaic (PV) system, reactive-power control methods for solar inverters have been considered. Among the various methods, the constant-voltage control outputs less reactive power compared with the other methods. We have developed a constant-voltage control to reduce the reactive-power output. However, the developed constant-voltage control still outputs unnecessary reactive power because the control parameter is constant in every waveform of the PV output. To reduce the reactive-power output, we propose a dynamic reactive-power control method with a PV output prediction. In the proposed method, the control parameter is varied according to the properties of the predicted PV waveform. In this study, we performed numerical simulations using a distribution system model, and we confirmed that the proposed method reduces the reactive-power output within the voltage constraint.
- Published
- 2016
41. Optimum Lubrication Conditions in Ironing of Stainless Steel Cup with Die Having Lubricant Pockets
- Author
-
Naoyuki Takahashi, Ken-ichiro Mori, W. Daodon, and Yohei Abe
- Subjects
0209 industrial biotechnology ,020303 mechanical engineering & transports ,020901 industrial engineering & automation ,Materials science ,0203 mechanical engineering ,Mechanics of Materials ,Mechanical Engineering ,Lubrication ,General Materials Science ,02 engineering and technology ,Surface finish ,Composite material - Published
- 2016
42. Method for Determining Line Drop Compensator Control Parameters of Low-Voltage Regulator Using Random Forest
- Author
-
Noriyuki Motegi, Jun Yoshinaga, Shinichi Kusagawa, Hiroshi Kikusato, Naoyuki Takahashi, Yasuhiro Hayashi, and Yu Fujimoto
- Subjects
Engineering ,business.industry ,Photovoltaic system ,Line (geometry) ,Regulator ,Electronic engineering ,Range (statistics) ,General Medicine ,business ,Low voltage ,Random forest ,Compensation (engineering) ,Voltage - Abstract
Compensation of a voltage within the appropriate range becomes difficult when a large number of photovoltaic (PV) systems are installed. As a solution to this problem, the installation of a low-voltage regulator (LVR) has been studied. In this paper, we propose a method for instantly and accurately determining the line drop compensator (LDC) method parameters as a part of a voltage management scheme, which consists of prediction, operation, and control. In the proposed method, the solution candidates of the proper LDC parameters are narrowed by using a random forest that learns the relationship between the power-series data and the properness of the LDC parameters, thereby reducing the computational cost. We performed numerical simulations to verify the validity of the proposed method. From the results, the LDC parameters can be rapidly and accurately determined. Additionally, the desirable voltage control performance is verified.
- Published
- 2015
43. Collective Migrations of Vascular Endothelial Cells under Hypoxic Flow Condition
- Author
-
Naoyuki TAKAHASHI, Daisuke YOSHINO, and Kenichi FUNAMOTO
- Published
- 2020
44. List of Contributors
- Author
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John S. Adams, Judith E. Adams, Jawaher A. Alsalem, Paul H. Anderson, Panagiota Andreopoulou, Edith Angellotti, Leggy A. Arnold, Gerald J. Atkins, Antonio Barbáchano, Shari S. Bassuk, Sarah Beaudin, Anna Y. Belorusova, Nancy A. Benkusky, Carlos Bernal-Mizrachi, Ishir Bhan, Harjit P. Bhattoa, Daniel D. Bikle, John P. Bilezikian, Neil C. Binkley, Heike A. Bischoff-Ferrari, Charles W. Bishop, Ida M. Boisen, Fabrizio Bonelli, Adele L. Boskey, Barbara J. Boucher, Roger Bouillon, Manuella Bouttier, Barbara D. Boyan, Danny Bruce, Laura Buburuzan, Andrew J. Burghardt, Thomas H.J. Burne, Mona S. Calvo, Carlos A. Camargo, Jorge B. Cannata-Andia, Margherita T. Cantorna, Carsten Carlberg, Geert Carmeliet, Thomas O. Carpenter, Graham D. Carter, Kevin D. Cashman, Lisa Ceglia, Sylvia Christakos, Kenneth B. Christopher, Rene F. Chun, Fredric L. Coe, Frederick Coffman, Juliet Compston, Cyrus Cooper, Elizabeth M. Curtis, Natalie E. Cusano, Michael Danilenko, G. David Roodman, Bess Dawson-Hughes, Pierre De Clercq, Hector F. DeLuca, Julie Demaret, Marie B. Demay, David W. Dempster, Elaine M. Dennison, Puneet Dhawan, Vassil Dimitrov, Katie M. Dixon, Maryam Doroudi, Shevaun M. Doyle, Adriana S. Dusso, Aleksey Dvorzhinskiy, Peter R. Ebeling, John A. Eisman, Gregory R. Emkey, Ervin H. Epstein Jr., Sol Epstein, Darryl Eyles, Murray J. Favus, David Feldman, Gemma Ferrer-Mayorga, David M. Findlay, James C. Fleet, Brian L. Foster, Renny T. Franceschi, David R. Fraser, Jessica M. Furst, Rachel I. Gafni, Edward Giovannucci, Christian M. Girgis, James L. Gleason, Francis H. Glorieux, Elzbieta Gocek, David Goltzman, José Manuel González-Sancho, Laura A. Graeff-Armas, William B. Grant, Natalie J. Groves, Conny Gysemans, Lasse Bøllehuus Hansen, Nicholas C. Harvey, Catherine M. Hawrylowicz, Colleen E. Hayes, Robert P. Heaney, Geoffrey N. Hendy, Pamela A. Hershberger, Martin Hewison, Michael F. Holick, Bruce W. Hollis, Philippe P. Hujoel, Elina Hyppönen, Karl L. Insogna, Nina G. Jablonski, Martin Blomberg Jensen, David A. Jolliffe, Glenville Jones, Kerry S. Jones, Harald Jüppner, Enikö Kallay, Andrew C. Karaplis, Martin Kaufmann, Mairead Kiely, Tiffany Y, Kim, Martin Konrad, Christopher S. Kovacs, Richard Kremer, Roland Krug, Rajiv Kumar, Noriyoshi Kurihara, Emma Laing, Joseph M. Lane, Dean P. Larner, María Jesús Larriba, Gilles Laverny, Nathalie Le Roy, Seong M. Lee, Michael A. Levine, Richard Lewis, Paul Lips, Thomas S. Lisse, Eva S. Liu, Philip T. Liu, Yan Li, Yan Chun Li, James G. MacKrell, Leila J. Mady, Sharmila Majumdar, Makoto Makishima, Peter J. Malloy, Elizabeth H. Mann, JoAnn E. Manson, Adrian R. Martineau, Rebecca S. Mason, Chantal Mathieu, Toshio Matsumoto, Donald G. Matthews, John J. McGrath, Daniel Metzger, Mark B. Meyer, Denshun Miao, Mathew T. Mizwicki, Rebecca J. Moon, Howard A. Morris, Li J. Mortensen, Alberto Muñoz, Yuko Nakamichi, Carmen J. Narvaez, Faye E. Nashold, Tally Naveh-Many, Carrie M. Nielson, Anthony W. Norman, Yves Nys, Melda Onal, Lubna Pal, Kristine Y. Patterson, Steven Pauwels, Pamela R. Pehrsson, Martin Petkovich, John M. Pettifor, Paul E. Pfeffer, Katherine M. Phillips, J. Wesley Pike, Stefan Pilz, Anastassios G. Pittas, Pawel Pludowski, David E. Prosser, Sri Ramulu N. Pullagura, L. Darryl Quarles, Rithwick Rajagopal, Katherine J. Ransohoff, Saaeha Rauz, Brian J. Rebolledo, Jörg Reichrath, Sandra Rieger, Amy E. Riek, Natacha Rochel, Jeffrey D. Roizen, Janet M. Roseland, Cliff Rosen, Mark S. Rybchyn, Hiroshi Saitoh, Reyhaneh Salehi-Tabar, Anne L. Schafer, Karl P. Schlingmann, Inez Schoenmakers, Zvi Schwartz, Kayla Scott, Christopher T. Sempos, Lusia Sepiashvili, Mukund Seshadri, Elizabeth Shane, Tatiana Shaurova, Irene Shui, Justin Silver, Ravinder J. Singh, Linda Skingle, René St-Arnaud, Jessica Starr, Keith R. Stayrook, Emily M. Stein, Ryan E. Stites, George P. Studzinski, Tatsuo Suda, Fumiaki Takahashi, Naoyuki Takahashi, Jean Y. Tang, Christine L. Taylor, Hugh S. Taylor, Peter J. Tebben, Thomas D. Thacher, Ravi Thadhani, Kebashni Thandrayen, Susan Thys-Jacobs, Dov Tiosano, Roberto Toni, Dwight A. Towler, Donald L. Trump, Nobuyuki Udagawa, André G. Uitterlinden, Aasis Unnanuntana, Jeroen van de Peppel, Bram C.J. van der Eerden, Marjolein van Driel, Johannes P.T.M. van Leeuwen, Natasja van Schoor, An-Sofie Vanherwegen, Aria Vazirnia, Lieve Verlinden, Annemieke Verstuyf, Reinhold Vieth, Carol L. Wagner, Graham R. Wallace, Connie Weaver, JoEllen Welsh, John H. White, Susan J. Whiting, Michael P. Whyte, John J. Wysolmerski, Sachiko Yamada, Olivia B. Yu, Kathryn Zavala, Christoph Zechner, Meltem Zeytinoglu, and Hengguang Zhao
- Published
- 2018
45. Osteoclastogenesis and Vitamin D
- Author
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Yuko Nakamichi, Tatsuo Suda, Naoyuki Takahashi, and Nobuyuki Udagawa
- Subjects
musculoskeletal diseases ,0301 basic medicine ,Bone mineral ,medicine.medical_specialty ,Chemistry ,Osteoporosis ,030209 endocrinology & metabolism ,Multiple modes ,medicine.disease ,Calcitriol receptor ,Bone resorption ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Conditional gene knockout ,medicine ,Vitamin D and neurology ,Homeostasis - Abstract
Vitamin D compounds, 1,25(OH)2D3 and its analogs, enhance osteoclastogenesis in vitro and in vivo through the vitamin D receptor (VDR) in osteoblastic cells. This proresorptive activity was detected only with much higher concentrations of vitamin D compounds than those expected in physiological conditions. On the other hand, these compounds have been used as therapeutic drugs in Japan for treating osteoporosis to increase bone mineral density (BMD). Notably, the increase in BMD by long-term treatment with pharmacological doses of vitamin D compounds is caused by the suppression of bone resorption. Therefore, whether vitamin D expresses proresorptive or antiresorptive properties seemingly depends on the treatment protocols. We established osteoblastic cell-specific and osteoclast-specific VDR conditional knockout mice. Neither VDR in osteoblastic cells nor that in osteoclasts plays important roles for osteoclastogenesis at homeostasis. However, VDR in osteoblastic cells, but not osteoclasts, was involved in the antiresorptive properties of pharmacological doses of vitamin D compounds in vivo. Multiple modes of action of vitamin D in bone resorption are discussed in detail in this chapter.
- Published
- 2018
46. Wnt16 regulates osteoclast differentiation in conjunction with Wnt5a
- Author
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Yasuhiro Kobayashi, Masanori Koide, Yukio Nakamura, Naoyuki Takahashi, Hiroyuki Kato, Nobuyuki Udagawa, Teruhito Yamashita, Shunsuke Uehara, and Gnanasagar J. Thirukonda
- Subjects
musculoskeletal diseases ,animal structures ,Biophysics ,Osteoclasts ,Biochemistry ,Wnt-5a Protein ,Bone resorption ,Mice ,Calcitriol ,Osteoprotegerin ,Osteoclast ,medicine ,Animals ,Receptor ,Molecular Biology ,Mice, Knockout ,biology ,Chemistry ,Wnt signaling pathway ,Cell Differentiation ,RANK Ligand ,Cell Biology ,Coculture Techniques ,Cell biology ,Wnt Proteins ,medicine.anatomical_structure ,RANKL ,biology.protein ,Signal transduction - Abstract
The canonical Wnt/β-catenin signaling pathway in osteoblast-lineage cells inhibits osteoclastogenesis through the expression of osteoprotegerin (Opg), a decoy receptor of receptor activator of Nf-κb (Rank) ligands. Wnt5a, a typical non-canonical Wnt ligand, enhances the expression of Rank in osteoclast precursors, which, in turn, promotes the Rank ligand (Rankl)-induced formation of osteoclasts. In contrast, Wnt16 and Wnt4 have been shown to inhibit the Rankl-induced formation of osteoclasts through non-canonical Wnt signals. However, the relationships among these Wnt ligands in osteoclastogenesis remained to be elucidated. We herein showed that Wnt16, but not Wnt4, inhibited the Rankl-induced osteoclastogenesis in bone marrow-derived macrophage (BMM) cultures. Wnt3a and Wnt4 inhibited the 1α,25-dihydroxy vitamin D3 (1,25D3)-induced osteoclastogenesis in co-cultures prepared from wild-type mice, but not in those from Opg–/– nice. Wnt16 inhibited the 1,25D3-induced formation of osteoclasts in both wild-type and Opg–/– co-cultures. Wnt16, Wnt4, and Wnt3a failed to inhibit the pit-forming activity of osteoclasts. Wnt16 failed to inhibit the Wnt5a-induced expression of Rank in osteoclast precursors. In contrast, Wnt5a abrogated the inhibitory effects of Wnt16 on Rankl-induced osteoclastogenesis. These results suggested that Wnt16 inhibited osteoclastogenesis, but not the function of osteoclasts and that Wnt16, an inhibitory Wnt ligand for osteoclastogenesis, regulates bone resorption in conjunction with Wnt5a.
- Published
- 2015
47. The dynamin inhibitor dynasore inhibits bone resorption by rapidly disrupting actin rings of osteoclasts
- Author
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Naoyuki Takahashi, Toshihide Mizoguchi, Yasuhiro Kobayashi, Kimitoshi Yagami, Gnanasagar J. Thirukonda, Shunsuke Uehara, Nobuyuki Udagawa, Teruhito Yamashita, Yukio Nakamura, and Takahiro Nakayama
- Subjects
Dynamins ,Male ,musculoskeletal diseases ,0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,Osteoclasts ,macromolecular substances ,GTPase ,Biology ,Bone resorption ,Mice ,03 medical and health sciences ,Endocrinology ,Osteoclast ,medicine ,Animals ,Orthopedics and Sports Medicine ,Bone Resorption ,Cells, Cultured ,Actin ,Dynamin ,RANK Ligand ,Hydrazones ,General Medicine ,Actin cytoskeleton ,Actins ,Resorption ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,RANKL ,biology.protein ,Female - Abstract
The cytoskeletal organization of osteoclasts is required for bone resorption. Binding of dynamin with guanosine triphosphate (GTP) was previously suggested to be required for the organization of the actin cytoskeleton. However, the role of the GTPase activity of dynamin in the organization of the actin cytoskeleton as well as in the bone-resorbing activity of osteoclasts remains unclear. This study investigated the effects of dynasore, an inhibitor of the GTPase activity of dynamin, on the bone-resorbing activity of and actin ring formation in mouse osteoclasts in vitro and in vivo. Dynasore inhibited the formation of resorption pits in osteoclast cultures by suppressing actin ring formation and rapidly disrupting actin rings in osteoclasts. A time-lapse image analysis showed that dynasore shrank actin rings in osteoclasts within 30 min. The intraperitoneal administration of dynasore inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced trabecular bone loss in mouse femurs. These in vitro and in vivo results suggest that the GTPase activity of dynamin is critical for the bone-resorbing activity of osteoclasts and that dynasore is a seed for the development of novel anti-resorbing agents.
- Published
- 2015
48. Method for Rapidly Determining Line Drop Compensator Parameters of Low-Voltage Regulator using Classifiers
- Author
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Noriyuki Motegi, Yasuhiro Hayashi, Yu Fujimoto, Jun Yoshinaga, Shinichi Kusagawa, Naoyuki Takahashi, and Hiroshi Kikusato
- Subjects
Distribution system ,Engineering ,business.industry ,Control theory ,Voltage control ,Regulator ,Energy Engineering and Power Technology ,Drop (telecommunication) ,Electrical and Electronic Engineering ,business ,Low voltage - Published
- 2015
49. Performance of an acoustically mixed pharmaceutical dry powder delivered from a novel inhaler
- Author
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Kazuhide Ashizawa, Ryoma Tanaka, Yusuke Hattori, Makoto Otsuka, Yasuaki Nakamura, and Naoyuki Takahashi
- Subjects
Materials science ,Drug Compounding ,Pharmaceutical Science ,02 engineering and technology ,Spectrum Analysis, Raman ,030226 pharmacology & pharmacy ,Excipients ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Rheology ,Microscopy ,Composite material ,Particle Size ,Salmeterol Xinafoate ,Inhaler ,Dry Powder Inhalers ,Acoustics ,021001 nanoscience & nanotechnology ,Bronchodilator Agents ,Dry powder ,symbols ,Microscopy, Electron, Scanning ,Fluticasone ,Particle size ,Spectrum analysis ,Powders ,0210 nano-technology ,Raman spectroscopy - Published
- 2017
50. Smart management system of customer's battery and heat pump water heater, considering the Japanese new rule for curtailment of PV output
- Author
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Hiroyuki Hatta, Tsuyoshi Ueno, Eitaro Omine, and Naoyuki Takahashi
- Subjects
Battery (electricity) ,Nameplate capacity ,Electric power system ,restrict ,business.industry ,Computer science ,Photovoltaic system ,Management system ,Electricity ,business ,Automotive engineering ,Power (physics) - Abstract
In Japan, the installed capacity of Photovoltaic(PV) generation systems reached about 30GW in 2015, in which there would be surplus power in whole power system in light load season. In order to install the PV system without affecting stable operation of power system, the Japanese government set a new rule to restrict PV output when the surplus power occurred in whole power system. Authors has developed operation and planning method of customers' appliances for utilizing surplus power of PV at the customer's side. To apply the new rule to restrict PV output for the developed method, improvement of the developed operation and planning method is necessary. This paper develops the improved operation and planning method of customers' appliances considering the new rule for PV output restriction. The simulation analysis has been conducted to validate the developed method. Simulation results shows that proposed method can reduce the customer's electricity bill by 10–20%, restricted energy of PV output by 10–20% when the selling rate of PV output is 9.27yen/kWh, which shows validity of proposed method.
- Published
- 2017
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