12 results on '"Katagiri, T."'
Search Results
2. Protein phosphatase magnesium-dependent 1A inhibits BMP signaling by stimulating Smad degradation independent of dephosphorylation at the carboxyl termini
- Author
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Kokabu, S., primary, Nojima, J., additional, Fukuda, T., additional, Kanomata, K., additional, Yoda, T., additional, and Katagiri, T., additional
- Published
- 2009
- Full Text
- View/download PDF
3. Subcloning of three osteoblastic cell lines with distinct differentiation phenotypes from the mouse osteoblastic cell line KS-4
- Author
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Yamashita, T., primary, Ishii, H., additional, Shimoda, K., additional, Sampath, T.K., additional, Katagiri, T., additional, Wada, M., additional, Osawa, T., additional, and Suda, T., additional
- Published
- 1996
- Full Text
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4. Enhancement of BMP signaling by cyclic AMP: Its role and mechanism
- Author
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Ohta, Y., Nakagawa, K., Imai, Y., Nomura, C., Katagiri, T., Koike, T., and Takaoka, K.
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- 2006
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5. Corrigendum to "Design of primers for direct sequencing of nine coding exons in the human ACVR1 gene" [Bone 138 (2020) 115469].
- Author
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Matsuoka M, Tsukamoto S, Orihara Y, Kawamura R, Kuratani M, Haga N, Ikebuchi K, and Katagiri T
- Published
- 2024
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- View/download PDF
6. Design of primers for direct sequencing of nine coding exons in the human ACVR1 gene.
- Author
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Matsuoka M, Tsukamoto S, Orihara Y, Kawamura R, Kuratani M, Haga N, Ikebuchi K, and Katagiri T
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- Heterozygote, Humans, Mutation genetics, Reproducibility of Results, Sequence Analysis, DNA, Activin Receptors, Type I genetics, DNA Primers, Exons, Myositis Ossificans genetics
- Abstract
The human ACVR1 gene encodes a transmembrane protein consisting of 509 amino acids called activin A receptor, type I (ACVR1) or activin receptor-like kinase 2 (ALK2) and has nine coding exons. The ALK2 protein functions as a signaling receptor for ligands of the transforming growth factor-β family. In the human ACVR1 gene, approximately 20 types of heterozygotic mutations in the coding exons have been associated with congenital disorders and somatic cancer, such as fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine glioma, diffuse idiopathic skeletal hyperostosis and some congenital heart disorders. In the present study, we designed primers for direct sequencing of the nine coding exons in the human ACVR1 gene. The reliability of the primers was examined by PCR and DNA sequencing using genomic DNA prepared from peripheral blood or swab samples of three patients with FOP who had different mutations in the ACVR1 gene. A single nucleotide heterozygotic mutation was identified in each genomic sample without additional mutations in other regions. Therefore, the primers designed for the nine coding exons of the ACVR1 gene could be useful for the genetic diagnosis of patients who may have disorders associated with mutations in the ACVR1 gene., Competing Interests: Declaration of competing interest T.K. received research grants from Daiichi-Sankyo, Co. Ltd. The other authors declare no conflicts of interest in association with the present study., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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7. Smad4-dependent transforming growth factor-β family signaling regulates the differentiation of dental epithelial cells in adult mouse incisors.
- Author
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Machiya A, Tsukamoto S, Ohte S, Kuratani M, Suda N, and Katagiri T
- Subjects
- Animals, Mice, Mice, Knockout, Cell Differentiation, Epithelial Cells, Incisor, Smad4 Protein physiology, TGF-beta Superfamily Proteins physiology
- Abstract
Teeth consist of two major tissues, enamel and dentin, which are formed during development by epithelial and mesenchymal cells, respectively. Rodent incisors are useful experimental models for studying the molecular mechanisms of tooth formation because they are simultaneously growing in not only embryos but also adults. Members of the transforming growth factor-β (TGF-β) family regulate epithelial-mesenchymal interactions through an essential coactivator, Smad4. In the present study, we established Smad4 conditional knockout (cKO) mice and examined phenotypes in adult incisors. Smad4 cKO mice died with severe anemia within one month. Phosphorylated Smad1/5/9 and Smad2/3 were detected in epithelial cells in both control and Smad4 cKO mice. Disorganized and hypoplastic epithelial cells, such as ameloblasts, were observed in Smad4 cKO mice. Moreover, alkaline phosphatase expression and iron accumulation were reduced in dental epithelial cells in Smad4 cKO mice. These findings suggest that TGF-β family signaling through Smad4 is required for the differentiation and functions of dental epithelial cells in adult mouse incisors., Competing Interests: Declaration of competing interest T. K. received research grants from Daiichi-Sankyo, Co., Ltd. The other authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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- View/download PDF
8. Functional characterization of a unique mutant of ALK2, p.K400E, that is associated with a skeletal disorder, diffuse idiopathic skeletal hyperostosis.
- Author
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Tsukamoto S, Kuratani M, and Katagiri T
- Subjects
- Bone Morphogenetic Proteins metabolism, Humans, Phosphorylation, Signal Transduction, Activin Receptors, Type I genetics, Activin Receptors, Type I metabolism, Hyperostosis, Diffuse Idiopathic Skeletal genetics, Myositis Ossificans genetics
- Abstract
Bone morphogenetic protein (BMP) signaling regulates the physiological and pathological development of skeletal tissues. Activin receptor-like kinase 2 (ALK2) is a BMP type I transmembrane serine/threonine kinase receptor. Recently, a p.K400E mutation was found in ALK2 in a patient with diffuse idiopathic skeletal hyperostosis (DISH), which is a disorder characterized by calcification and ossification of spinal ligaments and entheses. We report here the functional characterization of ALK2 p.K400E in vitro. Cells overexpressing ALK2 p.K400E activated BMP signaling in response to osteogenic BMP ligands. However, ALK2 p.K400E was not activated by a nonosteogenic ligand, Activin A. BMP signaling through ALK2 p.K400E was further enhanced by the coexpression of a BMP type II receptor. The type II receptor increased the phosphorylation level of ALK2 p.K400E, suggesting that ALK2 p.K400E is a hypersensitive mutant to the BMP type II receptor kinases. Our findings suggest that pathological calcification and ossification in DISH are caused by overactivated BMP signaling through ALK2 p.K400E enhanced by type II receptors in response to osteogenic BMPs rather than Activin A., Competing Interests: Declaration of competing interest T. K. received research grants from Daiichi-Sankyo, Co., Ltd. The other authors declare no conflicts of interest in association with the present study., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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- View/download PDF
9. Effects of FKBP12 and type II BMP receptors on signal transduction by ALK2 activating mutations associated with genetic disorders.
- Author
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Machiya A, Tsukamoto S, Ohte S, Kuratani M, Fujimoto M, Kumagai K, Osawa K, Suda N, Bullock AN, and Katagiri T
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- Animals, Bone Morphogenetic Proteins metabolism, Cell Line, Humans, Mice, Myositis Ossificans pathology, Ossification, Heterotopic genetics, Signal Transduction, Activin Receptors, Type I genetics, Bone Diseases, Developmental genetics, Bone Morphogenetic Protein Receptors, Type II physiology, Brain Stem Neoplasms genetics, Glioma genetics, Myositis Ossificans genetics, Tacrolimus Binding Protein 1A physiology
- Abstract
Various substitution mutations in ALK2, a transmembrane serine/threonine kinase receptor for bone morphogenetic proteins (BMPs), have been identified in patients with genetic disorders such as fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine glioma (DIPG) and heart defects. In this study, we characterized the ALK2 mutants R258G, G328V and F246Y, which were identified in patients with severe FOP, DIPG and unusual hereditary skeletal dysplasia, respectively. Both R258G and G328V were gain-of-function mutations, but F246Y was equivalent to wild-type ALK2. We also examined the effect of the suppressor FKBP12 on the signal transduction of a further 14 ALK2 mutations associated with FOP and/or DIPG. To varying extents FKBP12 over-expression suppressed the basal signaling induced by thirteen of the ALK2 mutants, whereas PF197-8L was uniquely resistant. In the PF197-8L mutant, the modelled ALK2 residue L197 induced a steric clash with the D36 residue in FKBP12 and dissociated their interaction. The co-expression of BMP type II receptors or stimulation with ligands relieved the suppression by FKBP12 by disrupting the interaction between mutant ALK2 and FKBP12. Taken together, FKBP12 binds to and suppresses mutant ALK2 proteins associated with FOP and DIPG, except for PF197-8L., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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10. Heterotopic bone induction via BMP signaling: Potential therapeutic targets for fibrodysplasia ossificans progressiva.
- Author
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Katagiri T, Tsukamoto S, and Kuratani M
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- Activin Receptors, Type I genetics, Animals, Bone Morphogenetic Proteins genetics, Bone Morphogenetic Proteins metabolism, Gene Expression Regulation genetics, Gene Expression Regulation physiology, Humans, Myositis Ossificans genetics, Signal Transduction genetics, Signal Transduction physiology, Activin Receptors, Type I metabolism, Myositis Ossificans metabolism
- Abstract
More than 50years ago, Marshal M. Urist detected "heterotopic bone-inducing activity" in demineralized bone matrix. This unique activity was referred to as "bone morphogenetic protein (BMP)" because it was sensitive to trypsin digestion. Purification of the bone-inducing activity from demineralized bone matrix using a bone-inducing assay in vivo indicated that the original "BMP" consisted of a mixture of new members of the transforming growth factor-β (TGF-β) family. The establishment of new in vitro assay systems that reflect the bone-inducing activity of BMPs in vivo have revealed the functional receptors and downstream effectors of BMPs. Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by progressive heterotopic bone formation in soft tissues similar to the event induced by the transplantation of BMPs in skeletal muscle. In patients with FOP, genetic mutations have been identified in the ACVR1 gene, which encodes the BMP receptor ALK2. The mutations in ALK2 associated with FOP are hypersensitive to type II receptor kinases. Recently, activin A, a non-osteogenic member of the TGF-β family, was identified as the ligand of the mutant ALK2 in FOP, and various types of signaling inhibitors for mutant ALK2 are currently under development to establish effective treatments for FOP., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
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11. Interaction of Tmem119 and the bone morphogenetic protein pathway in the commitment of myoblastic into osteoblastic cells.
- Author
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Tanaka K, Inoue Y, Hendy GN, Canaff L, Katagiri T, Kitazawa R, Komori T, Sugimoto T, Seino S, and Kaji H
- Subjects
- Animals, Blotting, Western, Bone Morphogenetic Protein 2 genetics, Bone Morphogenetic Protein 2 metabolism, Bone Morphogenetic Protein 4 genetics, Bone Morphogenetic Protein 4 metabolism, Bone Morphogenetic Proteins genetics, Cell Differentiation genetics, Cell Differentiation physiology, Cell Line, Humans, Membrane Proteins genetics, Mice, Myoblasts metabolism, Osteoblasts metabolism, Osteocalcin genetics, Osteocalcin metabolism, RNA, Small Interfering, Real-Time Polymerase Chain Reaction, Signal Transduction genetics, Signal Transduction physiology, Bone Morphogenetic Proteins metabolism, Membrane Proteins metabolism, Myoblasts cytology, Osteoblasts cytology
- Abstract
Bone morphogenetic proteins (BMPs) are critical for bone regeneration and induce ectopic bone formation in vivo. The constitutively activating mutation (R206H) of the BMP type 1 receptor, activin A type 1 receptor/activin-like kinase 2 (ACVR1/ALK2), underlies the molecular pathogenesis of fibrodysplasia ossificans progressiva (FOP) in which heterotopic ossification occurs in muscle tissue. In the present study, we performed a comparative DNA microarray analysis between stable empty vector- and ALK2(R206H)-transfected mouse myoblastic C2C12 cells. Forty genes were identified whose expression was increased >3.5 times in the experimental group versus the control. The bone formation-related factor, Tmem119, was included in this group. Osteoblast differentiation markers and mineralization were enhanced in C2C12 cells stably expressing Tmem119. Differentiation of myoblastic cells into myotubes was suppressed but differentiation into chondrocytes was little affected. Transcriptional activity of the BMP-2 signaling molecules, Smad1/5, was increased even in the absence of exogenous BMP-2. Endogenous BMP-2 levels positively correlated with Tmem119 levels. A BMP-2/4 neutralizing antibody and dorsomorphin, an ALK2 inhibitor, antagonized Tmem119-enhanced alkaline phosphatase (ALP) levels. Tmem119 siRNA antagonized the BMP-2-induced ALP and osteocalcin, but not Runx2 and Osterix, mRNAs, in C2C12 cells. In conclusion, Tmem119 levels were increased by the FOP-associated constitutively activating ALK2 mutation in myoblasts. The data show that Tmem119 promotes the differentiation of myoblasts into osteoblasts and the interaction with the BMP signaling pathway likely occurs downstream of Runx2 and Osterix in myoblasts. Tmem119 may play a critical role in the commitment of myoprogenitor cells to the osteoblast lineage., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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12. Ubc9 negatively regulates BMP-mediated osteoblastic differentiation in cultured cells.
- Author
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Yukita A, Hosoya A, Ito Y, Katagiri T, Asashima M, and Nakamura H
- Subjects
- Animals, Cell Differentiation genetics, Cell Line, Cells, Cultured, Gene Expression Profiling, Gene Knockdown Techniques, Male, Mice, Mice, Inbred C57BL, Osteoblasts drug effects, Phosphorylation drug effects, Protein Transport drug effects, RNA, Small Interfering metabolism, Recombinant Proteins pharmacology, Signal Transduction drug effects, Smad Proteins metabolism, Small Ubiquitin-Related Modifier Proteins metabolism, Sumoylation drug effects, Tibia drug effects, Tibia metabolism, Transcription, Genetic drug effects, Transforming Growth Factor beta metabolism, Up-Regulation drug effects, Bone Morphogenetic Protein 2 pharmacology, Cell Differentiation drug effects, Osteoblasts cytology, Osteoblasts enzymology, Transforming Growth Factor beta pharmacology, Ubiquitin-Conjugating Enzymes metabolism
- Abstract
SUMO (small ubiquitin-related modifier) modification (SUMOylation) has been reported to regulate various biological events such as cell-cycle progression, proliferation, and survival. Bone morphogenetic proteins (BMPs) play an important role in osteoblast differentiation and maturation. Although Smad4, which acts as a transcriptional factor in the BMP signaling, is a target of SUMOylation, the involvement of SUMOylation in osteoblast differentiation remains unclear. In this report, we demonstrated spatial expression patterns of SUMO proteins and Ubc9 (ubiquitin conjugating enzyme 9), which is a unique E2-SUMOylation enzyme, in mouse tibia. Furthermore, siRNA knockdown of Ubc9 enhanced osteoblastic differentiation induced by BMP2 in C2C12 mouse myoblasts and ST2 mouse bone-marrow derived stromal cells. Ubc9 knockdown elevated the BMP signaling transduction and reduced the expression of muscle-related genes in cooperation with BMP2. Finally, a luciferase assay using an Id1 (target gene of BMP signaling) reporter revealed that Smad4 mutants prevented from SUMOylation at their Lys158 possessed more potent transcriptional activity than wild-type Smad4. Taken together, these findings suggest that Ubc9 negatively regulates osteoblastic differentiation induced by BMP via, at least in part, SUMOylation of Smad4., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
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