16 results on '"Kii, Isao"'
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2. Synthesis of Functionalized Dibenzoazacyclooctynes by a Decomplexation Method for Dibenzo-Fused Cyclooctyne–Cobalt Complexes
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Sakata, Yuki, Nabekura, Ryoto, Hazama, Yuki, Hanya, Miho, Nishiyama, Takashi, Kii, Isao, and Hosoya, Takamitsu
- Abstract
A concise route for dibenzoazacyclooctynes (DIBACs) synthesis was developed based on Pictet–Spengler reaction and a novel cobalt decomplexation method established for dibenzo-fused cyclooctyne–cobalt complexes. The method allowed for the facile preparation of functionalized DIBACs, including bisDIBAC, which served as an efficient bisreactive linker for protein modification via the double-click reaction.
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- 2023
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3. Indolizines Enabling Rapid Uncaging of Alcohols and Carboxylic Acids by Red Light-Induced Photooxidation.
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Watanabe, Kenji, Terao, Nodoka, Kii, Isao, Nakagawa, Reiko, Niwa, Takashi, and Hosoya, Takamitsu
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- 2020
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4. Indolizines Enabling Rapid Uncaging of Alcohols and Carboxylic Acids by Red Light-Induced Photooxidation
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Watanabe, Kenji, Terao, Nodoka, Kii, Isao, Nakagawa, Reiko, Niwa, Takashi, and Hosoya, Takamitsu
- Abstract
The irradiation of red light-emitting-diode light (λ = 660 nm) to 3-acyl-2-methoxyindolizines in the presence of a catalytic amount of methylene blue triggered the photooxidation of the indolizine ring, resulting in a nearly quantitative release of alcohols or carboxylic acids within a few minutes. The method was applicable for photouncaging various functional molecules such as a carboxylic anticancer drug and a phenolic fluorescent dye from the corresponding indolizine conjugates, including an insulin–indolizine–dye conjugate.
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- 2020
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5. Periostin Deficiency Causes Severe and Lethal Lung Injury in Mice With Bleomycin Administration
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Kondoh, Hirofumi, Nishiyama, Takashi, Kikuchi, Yoshinao, Fukayama, Masashi, Saito, Mitsuru, Kii, Isao, and Kudo, Akira
- Abstract
Pulmonary capillary leakage followed by influx of blood fluid into the air space of lung alveoli is a crucial step in the progression of acute lung injury (ALI). This influx is due to increased permeability of the alveolar–capillary barrier. The extracellular matrix (ECM) between the capillary and the epithelium would be expected to be involved in prevention of the influx; however, the role of the ECM remains to be addressed. Here, we show that the ECM architecture organized by periostin, a matricellular protein, plays a pivotal role in the survival of bleomycin-exposed mice. Periostin was localized in the alveolar walls. Although periostin-null mice displayed no significant difference in lung histology and air–blood permeability, they exhibited early lethality in a model of bleomycin-induced lung injury, compared with their wild-type counterparts. This early lethality may have been due to increased pulmonary leakage of blood fluid into the air space in the bleomycin-exposed periostin-null mice. These results suggest that periostin in the ECM architecture prevents pulmonary leakage of blood fluid, thus increasing the survival rate in mice with ALI. Thus, this study provides an evidence for the protective role of the ECM architecture in the lung alveoli.
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- 2016
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6. Identification of a Dual Inhibitor of SRPK1 and CK2 That Attenuates Pathological Angiogenesis of Macular Degeneration in Mice
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Morooka, Satoshi, Hoshina, Mitsuteru, Kii, Isao, Okabe, Takayoshi, Kojima, Hirotatsu, Inoue, Naoko, Okuno, Yukiko, Denawa, Masatsugu, Yoshida, Suguru, Fukuhara, Junichi, Ninomiya, Kensuke, Ikura, Teikichi, Furuya, Toshio, Nagano, Tetsuo, Noda, Kousuke, Ishida, Susumu, Hosoya, Takamitsu, Ito, Nobutoshi, Yoshimura, Nagahisa, and Hagiwara, Masatoshi
- Abstract
Excessive angiogenesis contributes to numerous diseases, including cancer and blinding retinopathy. Antibodies against vascular endothelial growth factor (VEGF) have been approved and are widely used in clinical treatment. Our previous studies using SRPIN340, a small molecule inhibitor of SRPK1 (serine-arginine protein kinase 1), demonstrated that SRPK1 is a potential target for the development of antiangiogenic drugs. In this study, we solved the structure of SRPK1 bound to SRPIN340 by X-ray crystallography. Using pharmacophore docking models followed by in vitro kinase assays, we screened a large-scale chemical library, and thus identified a new inhibitor of SRPK1. This inhibitor, SRPIN803, prevented VEGF production more effectively than SRPIN340 owing to the dual inhibition of SRPK1 and CK2 (casein kinase 2). In a mouse model of age-related macular degeneration, topical administration of eye ointment containing SRPIN803 significantly inhibited choroidal neovascularization, suggesting a clinical potential of SRPIN803 as a topical ointment for ocular neovascularization. Thus SRPIN803 merits further investigation as a novel inhibitor of VEGF.
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- 2015
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7. Periostin, a novel marker of intramembranous ossification, is expressed in fibrous dysplasia and in c-Fos–overexpressing bone lesions.
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Kashima, Takeshi G., Nishiyama, Takashi, Shimazu, Kazuhiro, Shimazaki, Masashi, Kii, Isao, Grigoriadis, Agamemnon E., Fukayama, Masashi, and Kudo, Akira
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BIOMARKERS ,EXTRACELLULAR matrix proteins ,FIBROUS dysplasia of bone ,ONCOGENES ,GENE expression ,GENETIC mutation - Abstract
Summary: Fibrous dysplasia is a benign bone disease caused by a mutation in the gene for the stimulatory guanine nucleotide-binding protein Gsα, leading to high cyclic adenosine monophosphate levels. Histologically, fibrous dysplasia is characterized by the production of fibrous tissue accompanied by the deposition of ectopic type I collagen and other bone-associated extracellular matrix proteins, as well as by irregular woven intramembranous bone onto which type I collagen-containing Sharpey fibers are often attached. Fibrous dysplasia is also characterized by high expression of c-Fos/c-Jun, known targets for cyclic adenosine monophosphate signaling. In this study, we examined the expression of the bone-related extracellular matrix protein, periostin, and its known receptor, integrin αvβ3 (CD51/61), in normal bones as well as in fibrous dysplasia. Immunohistochemistry and in situ hybridization studies revealed that periostin was expressed in the extracellular matrix during intramembranous but not endochondral ossification, as well as in the fibrous component of fibrous dysplasia; and all cells adjacent to periostin-positive regions expressed CD51/61. Importantly, periostin was abundantly localized to Sharpey fibers. To investigate the contribution of c-Fos, we examined transgenic mice overexpressing c-fos, which develop sclerotic lesions closely resembling those found in fibrous dysplasia. In all lesions, transformed osteoblasts expressed high levels of periostin, whereas normal osteoblasts did not. Our results show that periostin is a novel marker for intramembranous ossification, and is a good candidate as a diagnostic tool and/or a therapeutic target in fibrous dysplasia. Moreover, the Gsα–cyclic adenosine monophosphate–c-Fos pathway might represent one mechanism of periostin up-regulation in fibrous dysplasia, resulting in altered collagen fibrillogenesis characteristic of this disease. [Copyright &y& Elsevier]
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- 2009
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8. The Niche Component Periostin Is Produced by Cancer-Associated Fibroblasts, Supporting Growth of Gastric Cancer through ERK Activation
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Kikuchi, Yoshinao, Kunita, Akiko, Iwata, Caname, Komura, Daisuke, Nishiyama, Takashi, Shimazu, Kazuhiro, Takeshita, Kimiko, Shibahara, Junji, Kii, Isao, Morishita, Yasuyuki, Yashiro, Masakazu, Hirakawa, Kosei, Miyazono, Kohei, Kudo, Akira, Fukayama, Masashi, and Kashima, Takeshi G.
- Abstract
Overexpression of periostin (POSTN), an extracellular matrix protein, has been observed in several cancers. We investigated the importance of POSTN in gastric cancer. Genome-wide gene expression analysis using publicly available microarray data sets revealed significantly high POSTN expression in cancer tissues from stage II–IV gastric cancer, compared with background normal tissues. The POSTN/vimentin mRNA expression ratio was highly associated with gene groups that regulate the cell cycle and cell proliferation. IHC showed that periglandular POSTN deposition, comprising linear deposition abutting the glandular epithelial cells in normal mucosa, disappeared during intestinal gastric cancer progression. Stromal POSTN deposition was also detected at the invasive front of intestinal-type and diffuse-type cancers. In situhybridization confirmed POSTN mRNA in cancer-associated fibroblasts, but not in tumor cells themselves. POSTN enhanced the in vitrogrowth of OCUM-2MLN and OCUM-12 diffuse-type gastric cancer cell lines, accompanied by the activation of ERK. Furthermore, coinoculation of gastric cancer cells with POSTN-expressing NIH3T3 mouse fibroblast cells facilitated tumor formation. The OCUM-2MLN orthotopic inoculation model demonstrated that tumors of the gastric wall in Postn−/−mice were significantly smaller than those in wild-type mice. Ki-67 and p-ERK positive rates were both lower in Postn−/−mice. These findings suggest that POSTN produced by cancer-associated fibroblasts constitutes a growth-supportive microenvironment for gastric cancer.
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- 2014
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9. Immunohistochemical localization of periostin in tooth and its surrounding tissues in mouse mandibles during development
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Suzuki, Hironobu, Amizuka, Norio, Kii, Isao, Kawano, Yoshiro, Nozawa-Inoue, Kayoko, Suzuki, Akiko, Yoshie, Hiromasa, Kudo, Akira, and Maeda, Takeyasu
- Abstract
Previous reports have shown expression of immunoreactivity for periostin, originally identified as osteoblast-specific factor-2, in the periosteum and periodontal ligament. However, the developmental changes in its expression and the detailed immunolocalization have remained veiled. The present study was undertaken to examine the spatiotemporal expression of this protein in teeth and their associated tissues of mice during development at light and electron microscopic levels. In tooth germs at cap stage, periostin immunoreactivity was recognizable in the interface between inner enamel epithelium and preodontoblasts as well as in the mesenchymal tissues around cervical loop. Dental follicles around tooth germs at bell stage localized periostin immunopositivity in addition to the immunopositive areas observed in cap-staged tooth germs, although the functional significance of periostin has remained unclear in tooth development. Furthermore, periostin immunoreactivity was also found in the alveolar bone surface. In the incisors of both 7- and 21-day-old mice, immunoreaction for periostin was discernible in the lingual periodontal ligament and labial fibrous tissue adjacent to the papillary layer. After postnatal day 7, immunoreaction for periostin came to be restricted to the fibrous bundles in the periodontal ligament in accordance with the organization of the periodontal fibers, indicating its localization matched the morphogenesis of the periodontal ligament. Immunoelectron microscopic observation of the mature periodontal ligament verified the localization of periostin between the cytoplasmic processes of periodontal fibroblasts and cementoblasts and the adjacent collagen fibrils. Our findings suggest that periostin is involved at the sites of the cell-to-matrix interaction, serving as adhesive equipment for bearing mechanical forces, including occlusal force and tooth eruption. © 2004 Wiley-Liss, Inc.
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- 2004
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10. Cell‐Cell Interaction Mediated by Cadherin‐11 Directly Regulates the Differentiation of Mesenchymal Cells Into the Cells of the Osteo‐Lineage and the Chondro‐Lineage
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Kii, Isao, Amizuka, Norio, Shimomura, Junko, Saga, Yumiko, and Kudo, Akira
- Abstract
We studied cadherin‐11 function in the differentiation of mesenchymal cells. Teratomas harboring the cadherin‐11gene generated bone and cartilage preferentially. Cadherin‐11 transfectants of C2C12 cells and cadherin‐11 and/or N‐cadherin transfectants of L cells showed that cadherin‐11 together with N‐cadherin‐induced expression of ALP and FGF receptor 2. These results suggest that cadherin‐11 directly regulates the differentiation of mesenchymal cells into the cells of the osteo‐lineage and the chondro‐lineage in a different manner from N‐cadherin.
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- 2004
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11. Cell‐Cell Interaction Mediated by Cadherin‐11 Directly Regulates the Differentiation of Mesenchymal Cells Into the Cells of the Osteo‐Lineage and the Chondro‐Lineage*
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Kii, Isao, Amizuka, Norio, Shimomura, Junko, Saga, Yumiko, and Kudo, Akira
- Abstract
We studied cadherin‐11 function in the differentiation of mesenchymal cells. Teratomas harboring the cadherin‐11gene generated bone and cartilage preferentially. Cadherin‐11 transfectants of C2C12 cells and cadherin‐11 and/or N‐cadherin transfectants of L cells showed that cadherin‐11 together with N‐cadherin‐induced expression of ALP and FGF receptor 2. These results suggest that cadherin‐11 directly regulates the differentiation of mesenchymal cells into the cells of the osteo‐lineage and the chondro‐lineage in a different manner from N‐cadherin.Introduction:Cell‐cell interaction is an essential event for tissue formation; however, the role of cell‐cell adhesion in mesenchymal tissue formation as well as in cell differentiation in this tissue remains unclear. cadherins, which are calcium‐dependent cell adhesion receptors, form adherence junctions after adherence and aggregation of cells. Because cadherin‐11 as well as N‐cadherin has been reported to be a mesenchyme‐related cadherin, we examined the cadherin‐11 action in teratomas and in the cell lines C2C12 and L cell. Herein, we show that cell‐cell interaction mediated by cadherin‐11 is responsible for bone and cartilage formation.Materials and Methods:It has been previously reported that N‐cadherin‐expressing E‐cadherin−/−ES transfectants formed neuroepithelium and cartilage in teratomas. Thus, we transfected the E‐cadherin−/−ES cell line with the cadherin‐11gene. Moreover, we also transfected C2C12 cells and L cells with the cadherin‐11gene for morphological analysis and study of the induced differentiation at the molecular level.Results and Conclusion:Teratomas derived from embryonic stem cells in which the cadherin‐11gene had been expressed exogenously contained bone and cartilage preferentially, showing that cadherin‐11 is involved in mesenchymal tissue formation, specifically in controlling the differentiation of these cells into osteoblasts and chondrocytes. Therefore, we further examined the functional difference between cadherin‐11 and N‐cadherin. The expression patterns of cadherin‐11 and N‐cadherin in cells of the mouse osteoblastic cell line MC3T3‐E1 showed that each cadherin was located independently of the cell‐cell adhesion site and acted individually. In hanging drop cultures, cadherin‐11 L cell transfectants aggregated in a sheet‐like structure, whereas N‐cadherin transfectants aggregated in a spherical form, indicating that each cadherin confers a different 3D architecture because of its individual adhesive property. To investigate the molecular mechanism of cadherin‐11 action in cell differentiation, we analyzed cadherin‐11 transfectants of C2C12 cells and cadherin‐11 and/or N‐cadherin transfectants of L cells and showed that cadherin‐11, together with N‐cadherin, induced expression of alkaline phosphatase (ALP) and fibroblast growth factor receptor 2. These results suggest that cadherin‐11 directly regulates the differentiation of mesenchymal cells into the cells of the osteo‐lineage and the chondro‐lineage in a different manner from N‐cadherin.
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- 2004
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12. A functional study on polymorphism of the ATP-binding cassette transporter ABCG2: critical role of arginine-482 in methotrexate transport
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MITOMO, Hideyuki, KATO, Ryo, ITO, Akiko, KASAMATSU, Shiho, IKEGAMI, Yoji, KII, Isao, KUDO, Akira, KOBATAKE, Eiry, SUMINO, Yasuhiro, and ISHIKAWA, Toshihisa
- Abstract
Overexpression of the ATP-binding cassette transporter ABCG2 reportedly causes multidrug resistance, whereas altered drug-resistance profiles and substrate specificity are implicated for certain variant forms of ABCG2. At least three variant forms of ABCG2 have been hitherto documented on the basis of their amino acid moieties (i.e., arginine, glycine and threonine) at position 482. In the present study we have generated those ABCG2 variants by site-directed mutagenesis and expressed them in HEK-293 cells. Exogenous expression of the Arg482, Gly482, and Thr482 variant forms of ABCG2 conferred HEK-293 cell resistance toward mitoxantrone 15-, 47- and 54-fold, respectively, as compared with mock-transfected HEK-293 cells. The transport activity of those variants was examined by using plasma-membrane vesicles prepared from ABCG2-overexpressing HEK-293 cells. [Arg482]ABCG2 transports [3H]methotrexate in an ATP-dependent manner; however, no transport activity was observed with the other variants (Gly482 and Thr482). Transport of methotrexate by [Arg482]ABCG2 was significantly inhibited by mitoxantrone, doxorubicin and rhodamine 123, but not by S-octylglutathione. Furthermore, ABCG2 was found to exist in the plasma membrane as a homodimer bound via cysteinyl disulphide bond(s). Treatment with mercaptoethanol decreased its apparent molecular mass from 140 to 70 kDa. Nevertheless, ATP-dependent transport of methotrexate by [Arg482]ABCG2 was little affected by such mercaptoethanol treatment. It is concluded that Arg482 is a critical amino acid moiety in the substrate specificity and transport of ABCG2 for certain drugs, such as methotrexate.
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- 2003
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13. Targeted Disruption of Cadherin‐11 Leads to a Reduction in Bone Density in Calvaria and Long Bone Metaphyses
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Kawaguchi, Jitsutaro, Azuma, Yoshiaki, Hoshi, Kazuto, Kii, Isao, Takeshita, Sunao, Ohta, Tomohiro, Ozawa, Hidehiro, Takeichi, Masatoshi, Chisaka, Osamu, and Kudo, Akira
- Abstract
The migration and adhesion of osteoblasts requires several classical cadherins. Cadherin‐11, one of the classical cadherins, was expressed in mouse osteoblasts in skull bone and femur, revealed by immunohistochemistry. To elucidate the function of cadherin‐11 in osteoblastogenesis, cadherin‐11 null mutant mice were investigated. Although apparently normal at birth, Alizarin red staining of null mutant mice showed a reduced calcified area at the frontal suture that caused a round‐shaped calvaria with increasing animal age to 3 months. Consequently, there was a reduction in bone density at the femoral metaphyses and the diploë of calvaria in null mutant mice. In the in vitro culture of newborn calvarial cells, the calcified area of mutant cells was smaller than those derived from wild‐type littermates. These results show that absence of cadherin‐11 leads to reduced bone density in some parts of skeletons including calvaria and long bone metaphyses, and thus suggest that cadherin‐11 plays roles in the regulation of osteoblast differentiation and in the mineralization of the osteoid matrix.
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- 2001
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14. Targeted Disruption of Cadherin‐11 Leads to a Reduction in Bone Density in Calvaria and Long Bone Metaphyses
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Kawaguchi, Jitsutaro, Azuma, Yoshiaki, Hoshi, Kazuto, Kii, Isao, Takeshita, Sunao, Ohta, Tomohiro, Ozawa, Hidehiro, Takeichi, Masatoshi, Chisaka, Osamu, and Kudo, Akira
- Abstract
The migration and adhesion of osteoblasts requires several classical cadherins. Cadherin‐11, one of the classical cadherins, was expressed in mouse osteoblasts in skull bone and femur, revealed by immunohistochemistry. To elucidate the function of cadherin‐11 in osteoblastogenesis, cadherin‐11 null mutant mice were investigated. Although apparently normal at birth, Alizarin red staining of null mutant mice showed a reduced calcified area at the frontal suture that caused a round‐shaped calvaria with increasing animal age to 3 months. Consequently, there was a reduction in bone density at the femoral metaphyses and the diploë of calvaria in null mutant mice. In the in vitro culture of newborn calvarial cells, the calcified area of mutant cells was smaller than those derived from wild‐type littermates. These results show that absence of cadherin‐11 leads to reduced bone density in some parts of skeletons including calvaria and long bone metaphyses, and thus suggest that cadherin‐11 plays roles in the regulation of osteoblast differentiation and in the mineralization of the osteoid matrix.
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- 2001
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15. The Transition of Cadherin Expression in Osteoblast Differentiation from Mesenchymal Cells: Consistent Expression of Cadherin‐11 in Osteoblast Lineage
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Kawaguchi, Jitsutaro, Kii, Isao, Sugiyama, Yutaro, Takeshita, Sunao, and Kudo, Akira
- Abstract
Osteoblasts are derived originally from pluripotent mesenchymal stem cells on migration into the bone matrix. To elucidate the contribution of classical cadherins in this differentiation pathway, we developed a new protocol for their analysis and studied their specific expressions in various cell lines of the mesenchymal lineage, including osteoblasts. N‐cadherin was expressed constitutively in all cell lines examined except an osteocyte‐like cell line whereas cadherin‐11 was expressed selectively in preosteoblast and preadipocyte cell lines. P‐cadherin also was expressed in primary cultures of calvarial cells and mature osteoblasts at a relatively low level compared with N‐cadherin and cadherin‐11. M‐cadherin was expressed only in a premyoblast cell line. We observed the transition of cadherin expression from M‐cadherin to cadherin‐11 in the premyoblast cell line when osteogenic differentiation was induced by treatment with bone morphogenetic protein 2 (BMP‐2), while the expression of N‐cadherin remained unchanged. In contrast, when a preadipocyte cell line, which shows a similar pattern of cadherin expression to osteoblasts, was induced to undergo adipogenic differentiation, the expression of N‐cadherin and cadherin‐11 was decreased. These observations characterize the cadherin expression profile of mesenchymal lineage cells, especially osteoblasts, which regularly express cadherin‐11. Cadherin‐11 may affect cell sorting, alignment, and separation through differentiation.
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- 2001
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16. The Transition of Cadherin Expression in Osteoblast Differentiation from Mesenchymal Cells: Consistent Expression of Cadherin‐11 in Osteoblast Lineage
- Author
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Kawaguchi, Jitsutaro, Kii, Isao, Sugiyama, Yutaro, Takeshita, Sunao, and Kudo, Akira
- Abstract
Osteoblasts are derived originally from pluripotent mesenchymal stem cells on migration into the bone matrix. To elucidate the contribution of classical cadherins in this differentiation pathway, we developed a new protocol for their analysis and studied their specific expressions in various cell lines of the mesenchymal lineage, including osteoblasts. N‐cadherin was expressed constitutively in all cell lines examined except an osteocyte‐like cell line whereas cadherin‐11 was expressed selectively in preosteoblast and preadipocyte cell lines. P‐cadherin also was expressed in primary cultures of calvarial cells and mature osteoblasts at a relatively low level compared with N‐cadherin and cadherin‐11. M‐cadherin was expressed only in a premyoblast cell line. We observed the transition of cadherin expression from M‐cadherin to cadherin‐11 in the premyoblast cell line when osteogenic differentiation was induced by treatment with bone morphogenetic protein 2 (BMP‐2), while the expression of N‐cadherin remained unchanged. In contrast, when a preadipocyte cell line, which shows a similar pattern of cadherin expression to osteoblasts, was induced to undergo adipogenic differentiation, the expression of N‐cadherin and cadherin‐11 was decreased. These observations characterize the cadherin expression profile of mesenchymal lineage cells, especially osteoblasts, which regularly express cadherin‐11. Cadherin‐11 may affect cell sorting, alignment, and separation through differentiation.
- Published
- 2001
- Full Text
- View/download PDF
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