start-ver=1.4
cd-journal=joma
no-vol=56
cd-vols=
no-issue=1
article-no=
start-page=25
end-page=29
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2002
dt-pub=200202
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Human BRAL1 and BCAN genes that belong to the link-module superfamily are tandemly arranged on chromosome 1q21-23.
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
We herein determined by fluorescence in situ hybridization the chromosomal localization of 2 human genes, BRAL1 and BCAN, both of which belong to the link-module superfamily, i.e. to the same band of chromosome 1q21-23. Further analysis of the genomic organization of BRAL1 and BCAN revealed that the BRAL1 gene was located 20-kb upstream of the BCAN start site. We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the BCAN gene. High heterozygosity (0.79) makes this polymorphism a useful marker in the study of genetic disorders. Knowledge of the structure of the genes and the marker provides essential information for further analysis of the gene locus at chromosome 1q21-23.
en-copyright=
kn-copyright=
en-aut-name=NomotoHiroyuki
en-aut-sei=Nomoto
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=HirakawaSatoshi
en-aut-sei=Hirakawa
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=UekiYasuyoshi
en-aut-sei=Ueki
en-aut-mei=Yasuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=OhtsukiHiroshi
en-aut-sei=Ohtsuki
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NinomiyaYoshifumi
en-aut-sei=Ninomiya
en-aut-mei=Yoshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
affil-num=1
en-affil=
kn-affil=Okayama University
affil-num=2
en-affil=
kn-affil=Okayama University
affil-num=3
en-affil=
kn-affil=Okayama University
affil-num=4
en-affil=
kn-affil=Okayama University
affil-num=5
en-affil=
kn-affil=Okayama University
affil-num=6
en-affil=
kn-affil=Okayama University
en-keyword=BRAL1
kn-keyword=BRAL1
en-keyword=BCAN
kn-keyword=BCAN
en-keyword=FISH
kn-keyword=FISH
en-keyword=schizophrenia
kn-keyword=schizophrenia
en-keyword=polymorphic marker
kn-keyword=polymorphic marker
END
start-ver=1.4
cd-journal=joma
no-vol=63
cd-vols=
no-issue=2
article-no=
start-page=79
end-page=85
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2009
dt-pub=200904
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The 3'-untranslated region of ADAMTS1 regulates its mRNA stability
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an inflammatory-induced gene. We have previously reported that ADAMTS1 was strongly but transiently expressed in the infarcted heart. In this study, we investigated whether a 3'-untranslated region (UTR) affects the mRNA stability of this gene. When stimulated with tissue necrosis factor (TNF)-alpha, the expression level of ADAMTS1 mRNA rapidly increased, but the induction of ADAMTS1 mRNA peaked at 6h after stimulation, after which the expression levels of ADAMTS1 mRNA decreased. The 3'-UTR ADAMTS1 mRNA contains multiple adenine and uridine-rich elements, suggesting that the 3'-UTR may regulate gene stability. The addition of actinomycin D, an RNA synthesis inhibitor, demonstrated the decay of induced ADAMTS1 mRNA by TNF-alpha. Furthermore, a region containing multiple AUUUA motifs within the ADAMTS1 3'-UTR destabilized transfected Enhanced Green Fluorescence Protein (EGFP) mRNA expression. These results demonstrated that the ADAMTS1 3'-UTR may regulate the expression of ADAMTS1 mRNA.
en-copyright=
kn-copyright=
en-aut-name=HatipogluOmer Faruk
en-aut-sei=Hatipoglu
en-aut-mei=Omer Faruk
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=HirohataSatoshi
en-aut-sei=Hirohata
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=YaykasliKursat Oguz
en-aut-sei=Yaykasli
en-aut-mei=Kursat Oguz
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=CilekMehmet Zeynel
en-aut-sei=Cilek
en-aut-mei=Mehmet Zeynel
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=DemircanKadir
en-aut-sei=Demircan
en-aut-mei=Kadir
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=ShinohataRyoko
en-aut-sei=Shinohata
en-aut-mei=Ryoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=YonezawaTomoko
en-aut-sei=Yonezawa
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KusachiShozo
en-aut-sei=Kusachi
en-aut-mei=Shozo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NinomiyaYoshifumi
en-aut-sei=Ninomiya
en-aut-mei=Yoshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=
kn-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=2
en-affil=
kn-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=3
en-affil=
kn-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=4
en-affil=
kn-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=5
en-affil=
kn-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=6
en-affil=
kn-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University
affil-num=7
en-affil=
kn-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=8
en-affil=
kn-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=9
en-affil=
kn-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University
affil-num=10
en-affil=
kn-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=ADAMTS1
kn-keyword=ADAMTS1
en-keyword=gene regulation
kn-keyword=gene regulation
en-keyword=metalloproteinase
kn-keyword=metalloproteinase
END
start-ver=1.4
cd-journal=joma
no-vol=69
cd-vols=
no-issue=3
article-no=
start-page=145
end-page=153
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2015
dt-pub=201506
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Eosinophil Cationic Protein Shows Survival Effect on H9c2 Cardiac Myoblast Cells with Enhanced Phosphorylation of ERK and Akt/GSK-3β under Oxidative Stress
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Eosinophil cationic protein (ECP) is well known as a cationic protein contained in the basic granules of activated eosinophils. Recent studies have reported that ECP exhibits novel activities on various types of cells, including rat neonatal cardiomyocytes. Here we evaluated the effects of ECP on rat cardiac myoblast H9c2 cells. Our results showed that ECP enhanced the survival of the cells, in part by promoting the ERK and Akt/GSK-3β signaling pathways. ECP attenuated the cytotoxic effects of H2O2 on H9c2 cells as well as the production of reactive oxygen species, the number of apoptotic cells and caspase 3/7 activity in the cells. In conclusion, ECP activated the ERK and Akt/GSK-3β pathways, resulting in anti-oxidative effects on H9c2 cells that attenuated apoptosis.
en-copyright=
kn-copyright=
en-aut-name=IshiiHiroko
en-aut-sei=Ishii
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KamikawaShigeshi
en-aut-sei=Kamikawa
en-aut-mei=Shigeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=HirohataSatoshi
en-aut-sei=Hirohata
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MizutaniAkifumi
en-aut-sei=Mizutani
en-aut-mei=Akifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=AbeKoji
en-aut-sei=Abe
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SenoMasaharu
en-aut-sei=Seno
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NinomiyaYoshifumi
en-aut-sei=Ninomiya
en-aut-mei=Yoshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
affil-num=1
en-affil=
kn-affil=Departments of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine
affil-num=2
en-affil=
kn-affil=Departments of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine
affil-num=3
en-affil=
kn-affil=Departments of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine
affil-num=4
en-affil=
kn-affil=Department of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University
affil-num=5
en-affil=
kn-affil=Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,
affil-num=6
en-affil=
kn-affil=Department of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University
affil-num=7
en-affil=
kn-affil=Departments of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine
affil-num=8
en-affil=
kn-affil=Departments of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine
en-keyword=ECP
kn-keyword=ECP
en-keyword=reactive oxygen species
kn-keyword=reactive oxygen species
en-keyword=Akt
kn-keyword=Akt
en-keyword=ERK
kn-keyword=ERK
END
start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=1992
dt-pub=19920328
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=カサノリ (Acetabularia acetabulum) に存在するCl一輸送性ATPaseに関する研究 反応機構・輸送機構の解明
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=
en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=大橋俊孝
kn-aut-sei=大橋
kn-aut-mei=俊孝
aut-affil-num=1
ORCID=
affil-num=1
en-affil=
kn-affil=岡山大学
END
start-ver=1.4
cd-journal=joma
no-vol=52
cd-vols=
no-issue=5
article-no=
start-page=1451
end-page=1460
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2005
dt-pub=20055
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=ADAMTS-9 is synergistically induced by interleukin-1 and tumor necrosis factor in OUMS-27 chondrosarcoma cells and in human chondrocytes
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objective
To compare induction of the aggrecanases (ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-8, ADAMTS-9, and ADAMTS-15) by interleukin-1 (IL-1) and tumor necrosis factor (TNF) 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-1 and/or TNF. Human chondrocytes obtained from osteoarthritic joints and human skin fibroblasts were also stimulated with IL-1 and/or TNF. 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-1-stimulated OUMS-27 cells was investigated.
Results
IL-1 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-1 stimulation was greater in chondrocytes than in fibroblasts. The combination of IL-1 and TNF had a synergistic effect, resulting in a considerable elevation in the level of ADAMTS9 mRNA. ADAMTS-9 protein was also induced in IL-1-stimulated OUMS-27 cells. The MAPK inhibitors SB203580 and PD98059 decreased ADAMTS9 up-regulation in OUMS-27 cells.
Conclusion
ADAMTS9 is an IL-1- and TNF-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.
en-copyright=
kn-copyright=
en-aut-name=DemircanKadir
en-aut-sei=Demircan
en-aut-mei=Kadir
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=HirohataSatoshi
en-aut-sei=Hirohata
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=NishidaKeiichiro
en-aut-sei=Nishida
en-aut-mei=Keiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=HatipogluOmer F.
en-aut-sei=Hatipoglu
en-aut-mei=Omer F.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=YonezawaTomoko
en-aut-sei=Yonezawa
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=ApteSuneel S.
en-aut-sei=Apte
en-aut-mei=Suneel S.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NinomiyaYoshifumi
en-aut-sei=Ninomiya
en-aut-mei=Yoshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
affil-num=1
en-affil=
kn-affil=Okayama University Graduate School of Medicine and Dentistry
affil-num=2
en-affil=
kn-affil=Okayama University Graduate School of Medicine and Dentistry
affil-num=3
en-affil=
kn-affil=Okayama University Graduate School of Medicine and Dentistry
affil-num=4
en-affil=
kn-affil=Okayama University Graduate School of Medicine and Dentistry
affil-num=5
en-affil=
kn-affil=Okayama University Graduate School of Medicine and Dentistry
affil-num=6
en-affil=
kn-affil=Okayama University Graduate School of Medicine and Dentistry
affil-num=7
en-affil=
kn-affil=Lerner Research Institute, Cleveland Clinic Foundation
affil-num=8
en-affil=
kn-affil=Okayama University Graduate School of Medicine and Dentistry
en-keyword=ADAMTS
kn-keyword=ADAMTS
en-keyword=aggrecanase
kn-keyword=aggrecanase
en-keyword=arthritis
kn-keyword=arthritis
en-keyword=chondrocyte
kn-keyword=chondrocyte
en-keyword=metalloproteinases
kn-keyword=metalloproteinases
en-keyword=IL-1
kn-keyword=IL-1
END
start-ver=1.4
cd-journal=joma
no-vol=124
cd-vols=
no-issue=1
article-no=
start-page=1
end-page=4
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20120401
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Perinodal ECM―its role in diffusion barrier formation and conduction velocity in the CNS
kn-title=ランビエ絞輪周囲のECMによるdiffusion barrier形成と跳躍伝導における役割
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=
en-aut-name=BekkuYoko
en-aut-sei=Bekku
en-aut-mei=Yoko
kn-aut-name=別宮洋子
kn-aut-sei=別宮
kn-aut-mei=洋子
aut-affil-num=1
ORCID=
en-aut-name=NinomiyaYoshifumi
en-aut-sei=Ninomiya
en-aut-mei=Yoshifumi
kn-aut-name=二宮善文
kn-aut-sei=二宮
kn-aut-mei=善文
aut-affil-num=2
ORCID=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=大橋俊孝
kn-aut-sei=大橋
kn-aut-mei=俊孝
aut-affil-num=3
ORCID=
affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 分子医化学
affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 分子医化学
affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 分子医化学
en-keyword=proteoglycan
kn-keyword=proteoglycan
en-keyword=node of Ranvier
kn-keyword=node of Ranvier
en-keyword=action potential
kn-keyword=action potential
en-keyword=extracellular space
kn-keyword=extracellular space
en-keyword=diffusion barrier
kn-keyword=diffusion barrier
END
start-ver=1.4
cd-journal=joma
no-vol=127
cd-vols=
no-issue=2
article-no=
start-page=103
end-page=109
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2015
dt-pub=20150803
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Role of COLXV/XVV gene, Multiplexin, as a basement membrane toolkit
kn-title=基底膜ツールキットとしてのXV/XVV型コラーゲン遺伝子の機能
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=大橋俊孝
kn-aut-sei=大橋
kn-aut-mei=俊孝
aut-affil-num=1
ORCID=
affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科
en-keyword=基底膜
kn-keyword=基底膜
en-keyword=ツールキット
kn-keyword=ツールキット
en-keyword=XV/XVV型コラーゲン
kn-keyword=XV/XVV型コラーゲン
en-keyword=プロテオグリカン
kn-keyword=プロテオグリカン
en-keyword=ミトコンドリア
kn-keyword=ミトコンドリア
END
start-ver=1.4
cd-journal=joma
no-vol=383
cd-vols=
no-issue=2
article-no=
start-page=111556
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20191015
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Mechanical strain attenuates cytokine-induced ADAMTS9 expression via transient receptor potential vanilloid type 1
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= The synovial fluids of patients with osteoarthritis (OA) contain elevated levels of inflammatory cytokines, which induce the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and of the matrix metalloproteinase (MMP) in chondrocytes. Mechanical strain has varying effects on organisms depending on the strength, cycle, and duration of the stressor; however, it is unclear under inflammatory stimulation how mechanical strain act on. Here, we show that mechanical strain attenuates inflammatory cytokine-induced expression of matrix-degrading enzymes. Cyclic tensile strain (CTS), as a mechanical stressor, attenuated interleukin (IL)-1β and tumor necrosis factor (TNF)-α-induced mRNA expression of ADAMTS4, ADAMTS9, and MMP-13 in normal chondrocytes (NHAC-kn) and in a chondrocytic cell line (OUMS-27). This effect was abolished by treating cells with mechano-gated channel inhibitors, such as gadolinium, transient receptor potential (TRP) family inhibitor, ruthenium red, and with pharmacological and small interfering RNA-mediated TRPV1 inhibition. Furthermore, nuclear factor κB (NF-κB) translocation from the cytoplasm to the nucleus resulting from cytokine stimulation was also abolished by CTS. These findings suggest that mechanosensors such as the TRPV protein are potential therapeutic targets in treating OA.
en-copyright=
kn-copyright=
en-aut-name=OhtsukiTakashi
en-aut-sei=Ohtsuki
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=ShinaokaAkira
en-aut-sei=Shinaoka
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=Kumagishi-ShinaokaKanae
en-aut-sei=Kumagishi-Shinaoka
en-aut-mei=Kanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=AsanoKeiichi
en-aut-sei=Asano
en-aut-mei=Keiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HatipogluOmer Faruk
en-aut-sei=Hatipoglu
en-aut-mei=Omer Faruk
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=InagakiJunko
en-aut-sei=Inagaki
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TakahashiKen
en-aut-sei=Takahashi
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=NishidaKeiichiro
en-aut-sei=Nishida
en-aut-mei=Keiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NaruseKeiji
en-aut-sei=Naruse
en-aut-mei=Keiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=HirohataSatoshi
en-aut-sei=Hirohata
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
affil-num=1
en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Cardiovascular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=21
cd-vols=
no-issue=19
article-no=
start-page=7028
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200924
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=BMP-2/beta-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Medication-related osteonecrosis of the jaw (MRONJ) is a severe pathological condition associated mainly with the long-term administration of bone resorption inhibitors, which are known to induce suppression of osteoclast activity and bone remodeling. Bone Morphogenetic Protein (BMP)-2 is known to be a strong inducer of bone remodeling, by directly regulating osteoblast differentiation and osteoclast activity. This study aimed to evaluate the effects of BMP-2 adsorbed onto beta-tricalcium phosphate (beta-TCP), which is an osteoinductive bioceramic material and allows space retention, on the prevention and treatment of MRONJ in mice. Tooth extraction was performed after 3 weeks of zoledronate (ZA) and cyclophosphamide (CY) administration. For prevention studies, BMP-2/beta-TCP was transplanted immediately after tooth extraction, and the mice were administered ZA and CY for an additional 4 weeks. The results showed that while the tooth extraction socket was mainly filled with a sparse tissue in the control group, bone formation was observed at the apex of the tooth extraction socket and was filled with a dense connective tissue rich in cellular components in the BMP-2/beta-TCP transplanted group. For treatment studies, BMP-2/beta-TCP was transplanted 2 weeks after tooth extraction, and bone formation was followed up for the subsequent 4 weeks under ZA and CY suspension. The results showed that although the tooth extraction socket was mainly filled with soft tissue in the control group, transplantation of BMP-2/beta-TCP could significantly accelerate bone formation, as shown by immunohistochemical analysis for osteopontin, and reduce the bone necrosis in tooth extraction sockets. These data suggest that the combination of BMP-2/beta-TCP could become a suitable therapy for the management of MRONJ.
en-copyright=
kn-copyright=
en-aut-name=MikaiAkihiro
en-aut-sei=Mikai
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OnoMitsuaki
en-aut-sei=Ono
en-aut-mei=Mitsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TosaIkue
en-aut-sei=Tosa
en-aut-mei=Ikue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=Ha Thi ThuNguyen
en-aut-sei=Ha Thi Thu
en-aut-mei=Nguyen
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HaraEmilio Satoshi
en-aut-sei=Hara
en-aut-mei=Emilio Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NoshoShuji
en-aut-sei=Nosho
en-aut-mei=Shuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=Kimura-OnoAya
en-aut-sei=Kimura-Ono
en-aut-mei=Aya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NawachiKumiko
en-aut-sei=Nawachi
en-aut-mei=Kumiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=TakaradaTakeshi
en-aut-sei=Takarada
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KubokiTakuo
en-aut-sei=Kuboki
en-aut-mei=Takuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
affil-num=1
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=BMP-2
kn-keyword=BMP-2
en-keyword=MRONJ
kn-keyword=MRONJ
en-keyword=bone regeneration
kn-keyword=bone regeneration
END
start-ver=1.4
cd-journal=joma
no-vol=21
cd-vols=
no-issue=21
article-no=
start-page=7967
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201027
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Distinct Osteogenic Potentials of BMP-2 and FGF-2 in Extramedullary and Medullary Microenvironments
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2) have been regarded as the major cytokines promoting bone formation, however, several studies have reported unexpected results with failure of bone formation or bone resorption of these growth factors. In this study, BMP-2 and FGF-2 adsorbed into atellocollagen sponges were transplanted into bone defects in the bone marrow-scarce calvaria (extramedullary environment) and bone marrow-abundant femur (medullary environment) for analysis of their in vivo effects not only on osteoblasts, osteoclasts but also on bone marrow cells. The results showed that BMP-2 induced high bone formation in the bone marrow-scarce calvaria, but induced bone resorption in the bone marrow-abundant femurs. On the other hand, FGF-2 showed opposite effects compared to those of BMP-2. Analysis of cellular dynamics revealed numerous osteoblasts and osteoclasts present in the newly-formed bone induced by BMP-2 in calvaria, but none were seen in either control or FGF-2-transplanted groups. On the other hand, in the femur, numerous osteoclasts were observed in the vicinity of the BMP-2 pellet, while a great number of osteoblasts were seen near the FGF-2 pellets or in the control group. Of note, FCM analysis showed that both BMP-2 and FGF-2 administrated in the femur did not significantly affect the hematopoietic cell population, indicating a relatively safe application of the two growth factors. Together, these results indicate that BMP-2 could be suitable for application in extramedullary bone regeneration, whereas FGF-2 could be suitable for application in medullary bone regeneration.
en-copyright=
kn-copyright=
en-aut-name=NoshoShuji
en-aut-sei=Nosho
en-aut-mei=Shuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=TosaIkue
en-aut-sei=Tosa
en-aut-mei=Ikue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OnoMitsuaki
en-aut-sei=Ono
en-aut-mei=Mitsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=HaraEmilio Satoshi
en-aut-sei=Hara
en-aut-mei=Emilio Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=IshibashiKei
en-aut-sei=Ishibashi
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=MikaiAkihiro
en-aut-sei=Mikai
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TanakaYukie
en-aut-sei=Tanaka
en-aut-mei=Yukie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=Kimura-OnoAya
en-aut-sei=Kimura-Ono
en-aut-mei=Aya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KomoriTaishi
en-aut-sei=Komori
en-aut-mei=Taishi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MaekawaKenji
en-aut-sei=Maekawa
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KubokiTakuo
en-aut-sei=Kuboki
en-aut-mei=Takuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
affil-num=1
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=BMP-2
kn-keyword=BMP-2
en-keyword=FGF-2
kn-keyword=FGF-2
en-keyword=bone formation
kn-keyword=bone formation
en-keyword=bone marrow
kn-keyword=bone marrow
END
start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=4
article-no=
start-page=e0249909
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210413
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Lack of collagen alpha 6(IV) chain in mice does not cause severe-to-profound hearing loss or cochlear malformation, a distinct phenotype from nonsyndromic hearing loss with COL4A6 missense mutation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Congenital hearing loss affects 1 in every 1000 births, with genetic mutations contributing to more than 50% of all cases. X-linked nonsyndromic hereditary hearing loss is associated with six loci (DFNX1-6) and five genes. Recently, the missense mutation (c.1771G>A, p.Gly591Ser) in COL4A6, encoding the basement membrane (BM) collagen alpha 6(IV) chain, was shown to be associated with X-linked congenital nonsyndromic hearing loss with cochlear malformation. However, the mechanism by which the COL4A6 mutation impacts hereditary hearing loss has not yet been elucidated. Herein, we investigated Col4a6 knockout (KO) effects on hearing function and cochlear formation in mice. Immunohistochemistry showed that the collagen alpha 6(IV) chain was distributed throughout the mouse cochlea within subepithelial BMs underlying the interdental cells, inner sulcus cells, basilar membrane, outer sulcus cells, root cells, Reissner's membrane, and perivascular BMs in the spiral limbus, spiral ligament, and stria vascularis. However, the click-evoked auditory brainstem response analysis did not show significant changes in the hearing threshold of Col4a6 KO mice compared with wild-type (WT) mice with the same genetic background. In addition, the cochlear structures of Col4a6 KO mice did not exhibit morphological alterations, according to the results of high-resolution micro-computed tomography and histology. Hence, loss of Col4a6 gene expression in mice showed normal click ABR thresholds and normal cochlear formation, which differs from humans with the COL4A6 missense mutation c.1771G>A, p.Gly591Ser. Therefore, the deleterious effects in the auditory system caused by the missense mutation in COL4A6 are likely due to the dominant-negative effects of the alpha 6(IV) chain and/or alpha 5 alpha 6 alpha 5(IV) heterotrimer with an aberrant structure that would not occur in cases with loss of gene expression.
en-copyright=
kn-copyright=
en-aut-name=TangShaoying
en-aut-sei=Tang
en-aut-mei=Shaoying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=YonezawaTomoko
en-aut-sei=Yonezawa
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MaedaYukihide
en-aut-sei=Maeda
en-aut-mei=Yukihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OnoMitsuaki
en-aut-sei=Ono
en-aut-mei=Mitsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MaebaTakahiro
en-aut-sei=Maeba
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=MiyoshiToru
en-aut-sei=Miyoshi
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MomotaRyusuke
en-aut-sei=Momota
en-aut-mei=Ryusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TomonoYasuko
en-aut-sei=Tomono
en-aut-mei=Yasuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Division of Molecular and Cell Biology, Shigei Medical Research Institute
kn-affil=
affil-num=9
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=
article-no=
start-page=730550
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210917
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Assessment of Possible Contributions of Hyaluronan and Proteoglycan Binding Link Protein 4 to Differential Perineuronal Net Formation at the Calyx of Held
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The calyx of Held is a giant nerve terminal mediating high-frequency excitatory input to principal cells of the medial nucleus of the trapezoid body (MNTB). MNTB principal neurons are enwrapped by densely organized extracellular matrix structures, known as perineuronal nets (PNNs). Emerging evidence indicates the importance of PNNs in synaptic transmission at the calyx of Held. Previously, a unique differential expression of aggrecan and brevican has been reported at this calyceal synapse. However, the role of hyaluronan and proteoglycan binding link proteins (HAPLNs) in PNN formation and synaptic transmission at this synapse remains elusive. This study aimed to assess immunohistochemical evidence for the effect of HAPLN4 on differential PNN formation at the calyx of Held. Genetic deletion of Hapln4 exhibited a clear ectopic shift of brevican localization from the perisynaptic space between the calyx of Held terminals and principal neurons to the neuropil surrounding the whole calyx of Held terminals. In contrast, aggrecan expression showed a consistent localization at the surrounding neuropil, together with HAPLN1 and tenascin-R, in both gene knockout (KO) and wild-type (WT) mice. An in situ proximity ligation assay demonstrated the molecular association of brevican with HAPLN4 in WT and HAPLN1 in gene KO mice. Further elucidation of the roles of HAPLN4 may highlight the developmental and physiological importance of PNN formation in the calyx of Held.
en-copyright=
kn-copyright=
en-aut-name=NojimaKojiro
en-aut-sei=Nojima
en-aut-mei=Kojiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=MiyazakiHaruko
en-aut-sei=Miyazaki
en-aut-mei=Haruko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=HoriTetsuya
en-aut-sei=Hori
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=VargovaLydia
en-aut-sei=Vargova
en-aut-mei=Lydia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
affil-num=1
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Cellular and Molecular Synaptic Function Unit, Okinawa Institute of Science and Technology Graduate University
kn-affil=
affil-num=4
en-affil=Department of Neuroscience, Charles University, Second Faculty of Medicine
kn-affil=
affil-num=5
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=perineuronal net
kn-keyword=perineuronal net
en-keyword=chondroitin sulfate proteoglycan
kn-keyword=chondroitin sulfate proteoglycan
en-keyword=calyx of Held
kn-keyword=calyx of Held
en-keyword=hyaluronan and proteoglycan binding link protein 4
kn-keyword=hyaluronan and proteoglycan binding link protein 4
en-keyword=synapse
kn-keyword=synapse
en-keyword=in situ proximity ligation assay
kn-keyword=in situ proximity ligation assay
END
start-ver=1.4
cd-journal=joma
no-vol=22
cd-vols=
no-issue=23
article-no=
start-page=12823
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20211126
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Suppression of Bone Necrosis around Tooth Extraction Socket in a MRONJ-like Mouse Model by E-rhBMP-2 Containing Artificial Bone Graft Administration
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Medication-related osteonecrosis of the jaw (MRONJ) is related to impaired bone healing conditions in the maxillomandibular bone region as a complication of bisphosphonate intake. Although there are several hypotheses for the onset of MRONJ symptoms, one of the possible causes is the inhibition of bone turnover and blood supply leading to bone necrosis. The optimal treatment strategy for MRONJ has not been established either. BMP-2, a member of the TGF-beta superfamily, is well known for regulating bone remodeling and homeostasis prenatally and postnatally. Therefore, the objectives of this study were to evaluate whether cyclophosphamide/zoledronate (CY/ZA) induces necrosis of the bone surrounding the tooth extraction socket, and to examine the therapeutic potential of BMP-2 in combination with the hard osteoinductive biomaterial, beta-tricalcium phosphate (beta-TCP), in the prevention and treatment of alveolar bone loss around the tooth extraction socket in MRONJ-like mice models. First, CY/ZA was intraperitoneally administered for three weeks, and alveolar bone necrosis was evaluated before and after tooth extraction. Next, the effect of BMP-2/beta-TCP was investigated in both MRONJ-like prevention and treatment models. In the prevention model, CY/ZA was continuously administered for four weeks after BMP-2/beta-TCP transplantation. In the treatment model, CY/ZA administration was suspended after transplantation of BMP-2/beta-TCP. The results showed that CY/ZA induced a significant decrease in the number of empty lacunae, a sign of bone necrosis, in the alveolar bone around the tooth extraction socket after tooth extraction. Histological analysis showed a significant decrease in the necrotic alveolar bone around tooth extraction sockets in the BMP-2/beta-TCP transplantation group compared to the non-transplanted control group in both MRONJ-like prevention and treatment models. However, bone mineral density, determined by micro-CT analysis, was significantly higher in the BMP-2/beta-TCP transplanted group than in the control group in the prevention model only. These results clarified that alveolar bone necrosis around tooth extraction sockets can be induced after surgical intervention under CY/ZA administration. In addition, transplantation of BMP-2/beta-TCP reduced the necrotic alveolar bone around the tooth extraction socket. Therefore, a combination of BMP-2/beta-TCP could be an alternative approach for both prevention and treatment of MRONJ-like symptoms.
en-copyright=
kn-copyright=
en-aut-name=TanakaYukie
en-aut-sei=Tanaka
en-aut-mei=Yukie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=AungKyaw Thu
en-aut-sei=Aung
en-aut-mei=Kyaw Thu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OnoMitsuaki
en-aut-sei=Ono
en-aut-mei=Mitsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MikaiAkihiro
en-aut-sei=Mikai
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=DangAnh Tuan
en-aut-sei=Dang
en-aut-mei=Anh Tuan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=HaraEmilio Satoshi
en-aut-sei=Hara
en-aut-mei=Emilio Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TosaIkue
en-aut-sei=Tosa
en-aut-mei=Ikue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=IshibashiKei
en-aut-sei=Ishibashi
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=Ono-KimuraAya
en-aut-sei=Ono-Kimura
en-aut-mei=Aya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NawachiKumiko
en-aut-sei=Nawachi
en-aut-mei=Kumiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KubokiTakuo
en-aut-sei=Kuboki
en-aut-mei=Takuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
affil-num=1
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Oral Rehabilitation and Implantology, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Oral Rehabilitation and Implantology, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Oral Rehabilitation and Implantology, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=medication-related osteonecrosis of the jaw
kn-keyword=medication-related osteonecrosis of the jaw
en-keyword=BMP-2
kn-keyword=BMP-2
en-keyword=beta-tricalcium phosphate
kn-keyword=beta-tricalcium phosphate
en-keyword=bone formation
kn-keyword=bone formation
en-keyword=bone necrosis
kn-keyword=bone necrosis
END
start-ver=1.4
cd-journal=joma
no-vol=17
cd-vols=
no-issue=11
article-no=
start-page=e0277307
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221117
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cysteinyl leukotriene receptor 1 is dispensable for osteoclast differentiation and bone resorption
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cysteinyl leukotriene receptor 1 (CysLTR1) is a G protein-coupled receptor for the inflammatory lipid mediators cysteinyl leukotrienes, which are involved in smooth muscle constriction, vascular permeability, and macrophage chemokine release. The Cysltr1 gene encoding CysLTR1 is expressed in the macrophage lineage, including osteoclasts, and the CysLTR1 antagonist Montelukast has been shown to suppress the formation of osteoclasts. However, it currently remains unclear whether CysLTR1 is involved in osteoclast differentiation and bone loss. Therefore, to clarify the role of CysLTR1 in osteoclastogenesis and pathological bone loss, we herein generated CysLTR1 loss-of-function mutant mice by disrupting the cysltr1 gene using the CRISPR-Cas9 system. These mutant mice had a frameshift mutation resulting in a premature stop codon (Cysltr1 KO) or an in-frame mutation causing the deletion of the first extracellular loop (Cysltr1(Delta 105)). Bone marrow macrophages (BMM) from these mutant mice lost the intracellular flux of calcium in response to leukotriene D-4, indicating that these mutants completely lost the activity of CysLTR1 without triggering genetic compensation. However, disruption of the Cysltr1 gene did not suppress the formation of osteoclasts from BMM in vitro. We also demonstrated that the CysLTR1 antagonist Montelukast suppressed the formation of osteoclasts without functional CysLTR1. On the other hand, disruption of the Cysltr1 gene partially suppressed the formation of osteoclasts stimulated by leukotriene D-4 and did not inhibit that by glutathione, functioning as a substrate in the synthesis of cysteinyl leukotrienes. Disruption of the Cysltr1 gene did not affect ovariectomy-induced osteoporosis or lipopolysaccharide-induced bone resorption. Collectively, these results suggest that the CysLT-CysLTR1 axis is dispensable for osteoclast differentiation in vitro and pathological bone loss, while the leukotriene D-4-CysTR1 axis is sufficient to stimulate osteoclast formation. We concluded that the effects of glutathione and Montelukast on osteoclast formation were independent of CysLTR1.
en-copyright=
kn-copyright=
en-aut-name=FujitaHirofumi
en-aut-sei=Fujita
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=AndoAoi
en-aut-sei=Ando
en-aut-mei=Aoi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MizusawaYohei
en-aut-sei=Mizusawa
en-aut-mei=Yohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OnoMitsuaki
en-aut-sei=Ono
en-aut-mei=Mitsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HattoriTakako
en-aut-sei=Hattori
en-aut-mei=Takako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=HabutaMunenori
en-aut-sei=Habuta
en-aut-mei=Munenori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KubotaSatoshi
en-aut-sei=Kubota
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=OhuchiHideyo
en-aut-sei=Ohuchi
en-aut-mei=Hideyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Department of Cytology and Histology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Faculty of Medicine, Okayama University Medical School
kn-affil=
affil-num=3
en-affil=Faculty of Medicine, Okayama University Medical School
kn-affil=
affil-num=4
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Biochemistry and Molecular Dentistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Cytology and Histology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=135
cd-vols=
no-issue=3
article-no=
start-page=174
end-page=174
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=The 55th Annual Meeting of the Japanese Society for Matrix Biology and Medicine
kn-title=第55回日本結合組織学会学術大会開催報告
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=
en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=大橋俊孝
kn-aut-sei=大橋
kn-aut-mei=俊孝
aut-affil-num=1
ORCID=
affil-num=1
en-affil=Department of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学学術研究院医歯薬学域 分子医化学
END