研究者詳細 - 大橋　俊孝

論文 - 大橋　俊孝

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Neurocan contributes to the molecular heterogeneity of the perinodal ECM. 査読

Yoko Bekku, Toshitaka Oohashi

Archives of histology and cytology 73 ( 2 ) 95 - 102 2010年

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：INT SOC HISTOLOGY & CYTOLOGY

Neurocan is a central nervous tissue-specific chondroitin sulfate proteoglycan of the lectican family. Mainly expressed during modeling and remodeling stages of this tissue, it is thought to play an important role via binding to various extracellular matrix and cellular components. In adults, neurocan expression is associated with the perineuronal net structures. This study shows the neurocan immunolocalization at the node of Ranvier in mouse central nervous tissues. The N-terminal fragment of neurocan (Ncan130) was the predominant form detected in the optic nerve. The expression of neurocan in the white matter of brain tissue and nerve tracts revealed differential expression profiles compared with those of versican V2 and brevican, other perinodal extracellular matrix molecules. Double immunolabeling for neurocan and a nodal marker, Bral1, or a paranodal marker, caspr, demonstrated that neurocan was localized at the node of Ranvier. Neurocan expression was found at many--not all--nodal regions, and neurocan-positive nodes outnumbered brevican-positive nodes. The nodal localization of neurocan was diminished in Bral1-deficient mice. Taken together, these findings indicate that neurocan contributes to the molecular heterogeneity of the perinodal matrix, and its nodal expression is dependent on Bral1.

DOI： 10.1679/aohc.73.95

Optical imaging of mouse articular cartilage using the glycosaminoglycans binding property of fluorescent-labeled octaarginine. 査読国際誌

K Inagawa, T Oohashi, K Nishida, J Minaguchi, T Tsubakishita, K O Yaykasli, A Ohtsuka, T Ozaki, T Moriguchi, Y Ninomiya

Osteoarthritis and cartilage 17 ( 9 ) 1209 - 18 2009年9月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: The aim of the current study was to examine the cartilage-specific binding property of polyarginine peptides (R4, 8, 12, and 16) and specifically to test octaarginine peptides for the optical imaging of articular cartilage in experimentally induced arthritis in mice. METHODS: Four rhodamine-labeled polyarginine peptides each with a different-length arginine chain (R4, 8, 12, or 16) were injected into the knee joints of C57BL/6J mice (n=20). The joints were excised 1h later and the fluorescent signal intensity in cartilage cryosections was compared for the four peptides. To examine the substrate of R8 in cartilage, femoral condyles obtained from another set of mice were treated with chondroitinase ABC (Ch'ase ABC), keratanase or heparitinase then immersed in R8-rhodamine. Fluorescent signals were examined by fluorescent microscopy. Next, R8-rhodamine was injected into the right knee joints of three control and three collagen antibody-induced arthritis (CAIA) mice, and fluorescent intensity in normal and degenerative cartilage was semi-quantitatively analysed on the histological sections using image software. Finally, femoral condyles from normal mice (n=2) and CAIA mice (n=2) were immersed in R8-rhodamine and calcein, then imaged using optical projection tomography (OPT). RESULTS: Fluorescent signals were specifically detected in the cartilage pericellular matrix from the surface to the tide mark but were completely absent in the calcified layer or bone marrow. The number of arginine residues significantly influenced peptide accumulation in articular cartilage, with R8 accumulating the most. The fluorescent signal in the femoral condylar cartilage diminished when it was treated with Ch'ase ABC. R8 accumulation was significantly decreased in the degenerative cartilage of CAIA mice, and this was demonstrated both histologically and in three-dimensional (3D)-reconstruction image by OPT. CONCLUSION: R8 may be a useful new experimental probe for optical imaging of normal and arthritic articular cartilage.

DOI： 10.1016/j.joca.2009.03.010

The 3’-untranslated region of ADAMTS1 regulates its mRNA stability. 査読

Hatipoglu OF, Hirohata S, Yaykasli KO, Cilek MZ, Demircan K, Shinohata R, Yonezawa T, Oohashi T, Kusachi S, Ninomiya Y

Acta Medica Okayama 63 ( 2 ) 79 - 85 2009年4月

Brevican distinctively assembles extracellular components at the large diameter nodes of Ranvier in the CNS. 査読国際誌

Yoko Bekku, Uwe Rauch, Yoshifumi Ninomiya, Toshitaka Oohashi

Journal of neurochemistry 108 ( 5 ) 1266 - 76 2009年3月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

Brevican is known to be an abundant extracellular matrix component in the adult brain and a structural constituent of perineuronal nets. We herein show that brevican, tenascin-R (TN-R) and phosphacan are present at the nodes of Ranvier on myelinated axons with a particularly large diameter in the central nervous system. A brevican deficiency resulted in a reorganization of the nodal matrices, which was characterized by the shift of TN-R, and concomitantly phosphacan, from an axonal diameter-dependent association with nodes to an axonal diameter independent association. Supported by the co-immunoprecipitation results, these observations indicate that the presence of TN-R and phosphacan at nodes is normally brevican-dependent, while in the absence of brevican these molecules can also be recruited by versican V2. The versican V2 and Bral1 distribution was not affected, thus indicating a brevican-independent role of these two molecules for establishing hyaluronan-binding matrices at the nodes. Our results revealed that brevican plays a crucial role in determining the specialization of the hyaluronan-binding nodal matrix assemblies in large diameter nodes.

DOI： 10.1111/j.1471-4159.2009.05873.x

ADAMTS9 activation by interleukin 1 beta via NFATc1 in OUMS-27 chondrosarcoma cells and in human chondrocytes. 査読国際誌

Kursat Oguz Yaykasli, Toshitaka Oohashi, Satoshi Hirohata, Omer Faruk Hatipoglu, Kiichi Inagawa, Kadir Demircan, Yoshifumi Ninomiya

Molecular and cellular biochemistry 323 ( 1-2 ) 69 - 79 2009年3月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

ADAMTS9 is a member of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes, with aggrecan-degrading activity. It has also been characterized to be reactive and highly activated ADAMTS by IL-1 beta in both chondrosarcoma cells and human chondrocytes (Demircan et al. Arthritis Rheum 52:1451-1460, 2005). In order to understand the regulation of ADAMTS9 gene expression a functional 3.0 kb human ADAMTS9 promoter has been cloned and characterized. A sequence analysis of the promoter revealed the presence of putative binding sites for Nuclear Factor of Activated T cells (NFAT), which is commonly found in the ADAMTS4 and ADAMTS5 promoters. NFATc1 was up-regulated in an activated form by IL-1 beta in human chondrocytes. The IL-1 beta inducible ADAMTS9 expression was inhibited by NFAT inhibitors, FK506 and 11Arg (11R)-VIVIT. Furthermore, direct binding of NFATc1 on distal and proximal promoters of ADAMTS9 was demonstrated by a chromatin immunoprecipitation assay. Promoter-reporter assays supported those results. These findings may provide a better understanding of the regulation of ADAMTS9 expression induced by inflammatory cytokines.

DOI： 10.1007/s11010-008-9965-4

THE ION-DIFFUSION BARRIER MODEL AT THE NODE OF RANVIER: FROM THE EXTRACELLULAR ION DIFFUSION ANALYSIS IN BRAL1-DEFICIENT MICE 査読

Yoko Bekku, Lydia Vargova, Yoshinobu Goto, Yoshifumi Ninomiya, Eva Sykova, Toshitaka Oohashi

JOURNAL OF PHYSIOLOGICAL SCIENCES 59 292 - 292 2009年

Target-tropic accumulation of SLX-liposome in arthritis mouse 査読

Minaguchi JA, Minematsu H, Oohashi T, Otani T, Inagawa K, Oie K, Nishida K, Ohtsuka A, Ninomiya Y, Igarashi K

Matrix Biology 27 43 - 43 2008年12月

Transvascular accumulation of Sialyl Lewis X conjugated liposome in inflamed joints of collagen antibody-induced arthritic (CAIA) mice. 査読

Jun Minaguchi, Toshitaka Oohashi, Kiichi Inagawa, Aiji Ohtsuka, Yoshifumi Ninomiya

Archives of histology and cytology 71 ( 3 ) 195 - 203 2008年11月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

The aim of the current study was to investigate the specific accumulation of the Sialyl Lewis X (SLX) liposome in inflammation in the collagen-antibody induced arthritic (CAIA) model mice. The SLX-liposome encapsulating fluorescent substance (Cy5.5 or Cy3) was prepared for this study. The SLX-liposome was administered intravenously via the mouse caudal vein. After 1 to 24 h, the accumulation of SLX-liposome was observed using in vivo fluorescent imaging equipment (eXplore Optix), or the knee joints were removed for histological analysis. The in vivo fluorescent imaging showed that the signal was confined to the inflammatory site in the CAIA mice in an inflammatory dependent manner. The signal intensity was stronger at 24 h than at 1 h after injection. In the histological sections, the fluorescent signals were detected in the periarticular soft-tissue, especially in the hyperplastic synovium, including a pannus invasion with inflammatory cells in the CAIA. Intense signals were observed in vessel-like structures 1 h after injection; these were co-labeled with the vascular endothelial cell marker (CD31) and E-selectin, a ligand of the SLX-liposome expressed on activated endothelial cells. The diffused signals from the vessels increased time-dependently at 6 to 24 h after injection. This is the first report to examine the exact localization of the SLXliposome by encapsulated fluorescence in hyperplastic synovial tissue of CAIA mice. These results suggest the feasibility and potential use of SLX-liposome as a vehicle for the active targeting of drug delivery to inflammatory tissue.

DOI： 10.1679/aohc.71.195

Molecular cloning and developmental expression of a hyaluronan and proteoglycan link protein gene, crtl1/hapln1, in zebrafish. 査読

Jeong Suk Kang, Yasuhiko Kawakami, Yoko Bekku, Yoshifumi Ninomiya, Juan Carlos Izpisúa Belmonte, Toshitaka Oohashi

Zoological science 25 ( 9 ) 912 - 8 2008年9月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）

The proteoglycan aggregate of the cartilage is composed of aggrecan, link protein (LP), and hyaluronan, providing resistance to compression in joints and cartilage structures. To further understand the function of LP during the process of chondrogenesis and bone formation in zebrafish, we cloned the zebrafish cDNA for hyaluronan and proteoglycan link protein 1 (crtl1/hapln1) and examined the expression of the gene during embryogenesis using in-situ hybridization. crtl1/hapln1 expression is first observed in the adaxial cells at the bud- stage. Throughout somitogenesis, crtl1/hapln1 is expressed in the sclerotomes, floor plate, and hypochord. In addition, crtl1/hapln1 is expressed in rhombomeres 3 and 5, pharyngeal arches, telecephalon, otic vesicles, and pectral fins. During chondrocranial/skull formation, crtl1/hapln1 expression is highest at around 4 dpf and is colocalized with aggrecan in the cartilaginous arches and with dermacan in the dermal bones.

DOI： 10.2108/zsj.25.912

Ten_m3 regulates eye-specific patterning in the mammalian visual pathway and is required for binocular vision. 査読国際誌

Catherine A Leamey, Sam Merlin, Paul Lattouf, Atomu Sawatari, Xiaohong Zhou, Natasha Demel, Kelly A Glendining, Toshitaka Oohashi, Mriganka Sur, Reinhard Fässler

PLoS biology 5 ( 9 ) e241 - 2092 2007年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PUBLIC LIBRARY SCIENCE

Binocular vision requires an exquisite matching of projections from each eye to form a cohesive representation of the visual world. Eye-specific inputs are anatomically segregated, but in register in the visual thalamus, and overlap within the binocular region of primary visual cortex. Here, we show that the transmembrane protein Ten_m3 regulates the alignment of ipsilateral and contralateral projections. It is expressed in a gradient in the developing visual pathway, which is consistently highest in regions that represent dorsal visual field. Mice that lack Ten_m3 show profound abnormalities in mapping of ipsilateral, but not contralateral, projections, and exhibit pronounced deficits when performing visually mediated behavioural tasks. It is likely that the functional deficits arise from the interocular mismatch, because they are reversed by acute monocular inactivation. We conclude that Ten_m3 plays a key regulatory role in the development of aligned binocular maps, which are required for normal vision.

DOI： 10.1371/journal.pbio.0050241

ADAMTS-9 is synergistically induced by interleukin-1beta and tumor necrosis factor alpha in OUMS-27 chondrosarcoma cells and in human chondrocytes. 査読国際誌

Kadir Demircan, Satoshi Hirohata, Keiichiro Nishida, Omer F Hatipoglu, Toshitaka Oohashi, Tomoko Yonezawa, Suneel S Apte, Yoshifumi Ninomiya

Arthritis and rheumatism 52 ( 5 ) 1451 - 60 2005年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-LISS

OBJECTIVE: To compare induction of the aggrecanases (ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-8, ADAMTS-9, and ADAMTS-15) by interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) in chondrocyte-like OUMS-27 cells and human chondrocytes, and to determine the mechanism of induction of the most responsive aggrecanase gene. METHODS: OUMS-27 cells were stimulated for different periods of time and with various concentrations of IL-1beta and/or TNFalpha. Human chondrocytes obtained from osteoarthritic joints and human skin fibroblasts were also stimulated with IL-1beta and/or TNFalpha. Total RNA was extracted, reverse transcribed, and analyzed by quantitative real-time polymerase chain reaction and Northern blotting. ADAMTS-9 protein was examined by Western blotting, and the role of the MAPK signaling pathway for ADAMTS9 induction in IL-1beta-stimulated OUMS-27 cells was investigated. RESULTS: IL-1beta increased messenger RNA (mRNA) levels of ADAMTS4, ADAMTS5, and ADAMTS9 but not ADAMTS1 and ADAMTS8. The fold increase for ADAMTS9 mRNA was greater than that for mRNA of the other aggrecanase genes. The increase of ADAMTS9 mRNA by IL-1beta stimulation was greater in chondrocytes than in fibroblasts. The combination of IL-1beta and TNFalpha had a synergistic effect, resulting in a considerable elevation in the level of ADAMTS9 mRNA. ADAMTS-9 protein was also induced in IL-1beta-stimulated OUMS-27 cells. The MAPK inhibitors SB203580 and PD98059 decreased ADAMTS9 up-regulation in OUMS-27 cells. CONCLUSION: ADAMTS9 is an IL-1beta- and TNFalpha-inducible gene that appears to be more responsive to these proinflammatory cytokines than are other aggrecanase genes. Furthermore, these cytokines had a synergistic effect on ADAMTS9. Together with the known ability of ADAMTS-9 to proteolytically degrade aggrecan and its potential to cleave other cartilage molecules, the data suggest that ADAMTS-9 may have a pathologic role in arthritis.

DOI： 10.1002/art.21010

Suppression of chondrosarcoma cells by 15-deoxy-Delta 12,14-prostaglandin J2 is associated with altered expression of Bax/Bcl-xL and p21. 査読国際誌

Zheng-Nan Shen, Keiichiro Nishida, Hideyuki Doi, Toshitaka Oohashi, Satoshi Hirohata, Toshifumi Ozaki, Aki Yoshida, Yoshifumi Ninomiya, Hajime Inoue

Biochemical and biophysical research communications 328 ( 2 ) 375 - 82 2005年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

We previously reported that 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), the most potent agonist for peroxisome proliferator-activated receptor gamma (PPAR gamma), induces apoptosis of human chondrosarcoma cell line OUMS-27. The current study aimed to explore the mechanism of 15d-PGJ(2)-induced apoptosis and inhibition of cell proliferation in OUMS-27 cells. The preliminary results of cDNA microarray analysis showed the down-regulation of anti-apoptotic Bcl-xL and up-regulation of pro-apoptotic Bax in the process of 15d-PGJ(2)-induced apoptosis. These changes were further confirmed at mRNA and protein levels by RT-PCR and Western blot analysis, respectively. Among cyclin-dependent kinase inhibitors, p21 was induced and up-regulated by 15d-PGJ(2), but p16 and p27 were not changed, suggesting that the involvement of p21 in inhibition of cell proliferation. Activation of caspase-3 by 15d-PGJ(2) was partly, but not completely, blocked by PPAR gamma antagonist (GW9662) suggesting the 15d-PGJ(2) exerted its effect by PPAR gamma-dependent and -independent pathways. Interestingly, immunohistochemical study on human chondrosarcoma samples revealed that Bcl-xL is frequently expressed by tumor cells. The results of the current study suggest that the potential ability of 15d-PGJ(2) in regulation of cell cycle and inhibition of Bcl-xL expression might be beneficial in the development of novel pharmacological agents for chondrosarcoma.

DOI： 10.1016/j.bbrc.2004.12.186

[Bral1, Bral2: the novel brain specific-hyaluronan and protoglycan link protein genes]. 査読

Toshitaka Oohashi, Yoko Bekku, Yoshifumi Ninomiya

Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 49 ( 15 Suppl ) 2354 - 61 2004年11月

Dynamic induction of ADAMTS1 gene in the early phase of acute myocardial infarction. 査読国際誌

Keigo Nakamura, Satoshi Hirohata, Takashi Murakami, Toru Miyoshi, Kadir Demircan, Toshitaka Oohashi, Hiroko Ogawa, Kazuya Koten, Kenichi Toeda, Shozo Kusachi, Yoshifumi Ninomiya, Yasushi Shiratori

Journal of biochemistry 136 ( 4 ) 439 - 46 2004年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPANESE BIOCHEMICAL SOC

Extracellular matrix (ECM)-degrading enzymes such as matrix metalloproteases (MMPs) play an essential role in the repair of infarcted tissue, which affects ventricular remodeling after myocardial infarction. ADAMTS1 (A disintegrin and metalloprotease with thrombospondin motifs), a newly discovered metalloprotease, was originally cloned from a cancer cell line, but little is known about its contribution to disease. To test the hypothesis that ADAMTS1 appears in infarcted myocardial tissue, we examined ADAMTS1 mRNA expression in a rat myocardial infarction model by Northern blotting, real-time RT-PCR and in situ hybridization. Normal endothelium expressed little ADAMTS1 mRNA, while normal myocardium expressed no detectable ADAMTS1 mRNA. Up-regulation of ADAMTS1 was demonstrated by Northern blot analysis and real-time RT-PCR at 3 h after coronary artery ligation. In situ hybridization revealed strong ADAMTS1 mRNA signals in the endothelium and myocardium in the infarcted heart, mainly in the infarct zone, at 3 h after myocardial infarction. The rapid and transient up-regulation of the ADAMTS1 gene in the ischemic heart was distinct from the regulatory patterns of other MMPs. Our study demonstrated that the ADAMTS1 gene is a new early immediate gene expressed in the ischemic endothelium and myocardium.

DOI： 10.1093/jb/mvh138

Lp3/Hapln3, a novel link protein that co-localizes with versican and is coordinately up-regulated by platelet-derived growth factor in arterial smooth muscle cells. 査読国際誌

Hiroko Ogawa, Toshitaka Oohashi, Masataka Sata, Yoko Bekku, Satoshi Hirohata, Keigo Nakamura, Tomoko Yonezawa, Shozo Kusachi, Yasushi Shiratori, Yoshifumi Ninomiya

Matrix biology : journal of the International Society for Matrix Biology 23 ( 5 ) 287 - 98 2004年8月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE BV

Link proteins (LPs) belong to the link-module superfamily, which can stabilize and enhance the binding of lecticans to hyaluronan. We report here the identification and characterization of a novel rat link protein gene (Lp3/Hapln3). The deduced protein sequence shares the typical modular elements of link proteins and has an estimated mass of 39 kDa. Examination of the rat genomic DNA sequence revealed that Lp3/Hapln3 and aggrecan genes were paired on chromosome 1q31. Another LP gene and the lectican gene were also paired at a different locus, as they are in the human and mouse genomes. Immunohistochemical analysis showed the prominent expression of Lp3/Hapln3 in the smooth muscle tissues of the vascular wall and gastrointestinal tract. Further comparative studies revealed that Lp3/Hapln3 was well co-localized with versican around the smooth muscle cells of blood vessels but not around endothelial cells. In vitro experiments using primary cultured rat arterial smooth muscle cells (ASMCs) demonstrated the coordinated up-regulation of Lp3/Hapln3 and versican by platelet-derived growth factor (PDGF). These data were supported by in vivo studies of a mechanical vascular injury model in mice. Altogether, our results suggest that Lp3/Hapln3 is involved, together with versican and hyaluronan, in the formation of the pericellular matrix of vascular smooth muscle cells.

DOI： 10.1016/j.matbio.2004.07.001

Characterization of dermacan, a novel zebrafish lectican gene, expressed in dermal bones. 査読国際誌

Jeong Suk Kang, Toshitaka Oohashi, Yasuhiko Kawakami, Yoko Bekku, Juan Carlos Izpisúa Belmonte, Yoshifumi Ninomiya

Mechanisms of development 121 ( 3 ) 301 - 12 2004年3月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE BV

We report here the isolation and characterization of a cDNA encoding zebrafish dermacan, a novel member of hyaluronan (HA)-binding proteoglycans, which was termed after its characteristic expression in the zebrafish dermal bones. The deduced protein sequence shares the typical modular elements of lecticans. Sequence comparison covering the C-terminal globular domain demonstrated that dermacan shows high homology with zebrafish versican but is distinct from any other identified lecticans. Genomic DNA analysis demonstrated that dermacan and versican were encoded by distinct genes in the zebrafish genome. The expression of dermacan is initiated in the sclerotome and cephalic paraxial mesoderm at 16 h postfertilization. During the pharyngular period, dermacan transcripts were detected in the sclerotome, tail fin bud, pharyngular arch primordial region, and otic vesicle. In the development of craniofacial bones, dermacan expression was detected typically in the opercle and dentary. These regions belong to the craniofacial dermal bones. aggrecan expression, in contrast, was observed in the elements of craniofacial cartilage bones. In the dermacan-morpholino-injected embryos, dermal bones, e.g. opercle, dentary, and branchiostegal rays, as well as axial skeleton in the trunk, showed decreased ossification. We conclude that dermacan is a novel lectican gene, and that zebrafish lectican genes have genetically diverged. In addition, our data suggest the involvement of dermacan in zebrafish dermal bone development.

DOI： 10.1016/j.mod.2004.01.007

Cartilage link protein interacts with neurocan, which shows hyaluronan binding characteristics different from CD44 and TSG-6. 査読国際誌

Uwe Rauch, Satoshi Hirakawa, Toshitaka Oohashi, Joachim Kappler, Gunnel Roos

Matrix biology : journal of the International Society for Matrix Biology 22 ( 8 ) 629 - 39 2004年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE BV

The interaction of neurocan with hyaluronan was qualitatively characterized with alkaline phosphatase fusion proteins secreted by mammalian cells. The wild type neurocan hyaluronan binding domain fused to alkaline phosphatase bound to immobilized hyaluronan under physiological as well as moderately hypertonic conditions, whereas its ability to bind to immobilized chondroitin sulfate dropped rapidly with increasing salt concentration. Strong hyaluronan binding ability was still evident when in both link modules within the hyaluronan binding domain a basic amino acid was mutated, which is well conserved among link modules of hyaluronan binding proteins. A strong enhancement of the binding of neurocan to immobilized hyaluronan was observed after preincubation of the immobilized hyaluronan with cartilage link protein. Moreover, this preincubation mediated also the binding of a fusion protein representing only the immunoglobulin module of neurocan linked to alkaline phosphatase, which showed no binding to immobilized hyaluronan alone. The interaction of the neurocan immunoglobulin module with link protein could also be shown by overlay blot analysis. These observations suggest that the hyaluronan binding characteristics of paired link modules are different from those of single link modules, and that the reported temporal co-expression of cartilage link protein and of neurocan in developing brain implicates the possibility of a cooperative function of these molecules.

DOI： 10.1016/j.matbio.2003.11.007

Molecular cloning of Bral2, a novel brain-specific link protein, and immunohistochemical colocalization with brevican in perineuronal nets. 査読国際誌

Yoko Bekku, Wei-Dong Su, Satoshi Hirakawa, Reinhard Fässler, Aiji Ohtsuka, Jeong Suk Kang, Jennifer Sanders, Takuro Murakami, Yoshifumi Ninomiya, Toshitaka Oohashi

Molecular and cellular neurosciences 24 ( 1 ) 148 - 59 2003年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The hyaluronan binding chondroitin sulphate proteoglycans, called lecticans, are the abundant extracellular matrix molecules in the developing and/or adult brain. The link proteins (LPs) are also known to be coordinately present in brain. We report here the molecular cloning and expression analysis of a novel member of LPs: Bral2, predominantly expressed in brain. The Bral2 mRNA expression is first detected at P20 and continued through adulthood, suggesting its functional importance and association with adult-type lecticans. The substantial immunoreactivity of Bral2 is found in several nuclei throughout the midbrain and hindbrain in a perineuronal net pattern. In situ hybridization revealed that Bral2 is synthesized by these neurons themselves, especially by the GABAergic neurons in the cerebellar cortex. Interestingly, the colocalization and synergic importance of Bral2 and brevican in the perineuronal nets is indicated by the comparative immunohistochemical analysis using wild-type and brevican-deficient mouse brain. Our results suggest that Bral2 is involved in the formation of extracellular matrix contributing to perineuronal nets and facilitate the understanding of a functional role of these extracellular matrices.

Molecular cloning of a novel transmembrane protein MOLT expressed by mature oligodendrocytes. 査読国際誌

Hiroyuki Nomoto, Tomoko Yonezawa, Kouichi Itoh, Katsuhiko Ono, Kiyotaka Yamamoto, Toshitaka Oohashi, Fumio Shiraga, Hiroshi Ohtsuki, Yoshifumi Ninomiya

Journal of biochemistry 134 ( 2 ) 231 - 8 2003年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

A novel oligodendrocyte (OL)-specific cDNA was isolated from brain capillary endothelial cells and characterized. The cDNA encodes a protein of 1099 amino acids that contains a signal peptide and a transmembrane domain. The protein was expressed in mature OLs in vivo and in vitro cell cultures and was thus designated as mature OL transmembrane protein (MOLT). RT-PCR analysis showed that MOLT mRNA was expressed in brain, lung, pancreas, and testis. A polyclonal antibody raised against a part of the mouse MOLT reacted specifically with multipolar OLs possessing radially oriented processes that penetrated into the gray matter. More cells were detected in the white matter, and these had longitudinally oriented processes. In a rat OL lineage culture system, oligodendrocyte precursor cells did not initially produce MOLT mRNA and protein, but when they begun to differentiate into mature OLs, they started expressing MOLT. Consequently, MOLT may function as OLs become mature and may serve as a cell-surface marker for OL differentiation.

The murine Ten-m/Odz genes show distinct but overlapping expression patterns during development and in adult brain. 査読国際誌

Xiao-Hong Zhou, Oliver Brandau, Kang Feng, Toshitaka Oohashi, Yoshifumi Ninomiya, Uwe Rauch, Reinhard Fässler

Gene expression patterns : GEP 3 ( 4 ) 397 - 405 2003年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

The mouse TEN-M/ODZ proteins belong to a new family of type II transmembrane proteins with unknown function. The family consists of four members, which are expressed highly in brain and less in many other tissues. In the present study we have generated specific RNA probes and antibodies to characterize the expression of the 4 Ten-m/Odz genes in the developing and adult central nervous system (CNS) of mice. Ten-m/Odz3 and Ten-m/Odz4 mRNAs were first detectable at E7.5, Ten-m/Odz2 expression started at the 37 somite (E 10.5) stage, while Ten-m/Odz1 mRNA is not found before E15.5. In the adult mouse CNS mRNAs of the 4 Ten-m/Odzs were expressed in distinct patterns, which partially overlapped. Immunostaining and in situ hybridization localized proteins and mRNAs of Ten-m/Odzs in adjacent areas suggesting that TEN-M/ODZ proteins might be transported from the cell body along the axon or that they are shed from the cell surface and diffuse into distant regions.

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