start-ver=1.4
cd-journal=joma
no-vol=25
cd-vols=
no-issue=12
article-no=
start-page=6648
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240617
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Local E-rhBMP-2/β-TCP Application Rescues Osteocyte Dendritic Integrity and Reduces Microstructural Damage in Alveolar Bone Post-Extraction in MRONJ-like Mouse Model
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/beta-Tricalcium phosphate (E-rhBMP-2/beta-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/beta-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/beta-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/beta-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ.
en-copyright=
kn-copyright=
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=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=WangZiyi
en-aut-sei=Wang
en-aut-mei=Ziyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=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=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=KitagawaWakana
en-aut-sei=Kitagawa
en-aut-mei=Wakana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
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=9
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=10
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 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 Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Advanced Research Center for Oral and Craniofacial Sciences, 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 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 Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
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=osteocyte dendritic network
kn-keyword=osteocyte dendritic network
en-keyword=microcrack accumulation
kn-keyword=microcrack accumulation
en-keyword=bone remodeling
kn-keyword=bone remodeling
END
start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=10
article-no=
start-page=807
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240509
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The oral mucosa functions as a physico-chemical and immune barrier to external stimuli, and an adequate width of the keratinized mucosa around the teeth or implants is crucial to maintaining them in a healthy and stable condition. In this study, for the first time, bulk RNA-seq analysis was performed to explore the gene expression of laser microdissected epithelium and lamina propria from mice, aiming to investigate the differences between keratinized and non-keratinized oral mucosa. Based on the differentially expressed genes (DEGs) and Gene Ontology (GO) Enrichment Analysis, bone morphogenetic protein 2 (BMP-2) was identified to be a potential regulator of oral mucosal keratinization. Monoculture and epithelial-mesenchymal cell co-culture models in the air-liquid interface (ALI) indicated that BMP-2 has direct and positive effects on epithelial keratinization and proliferation. We further performed bulk RNA-seq of the ALI monoculture stimulated with BMP-2 in an attempt to identify the downstream factors promoting epithelial keratinization and proliferation. Analysis of the DEGs identified, among others, IGF2, ID1, LTBP1, LOX, SERPINE1, IL24, and MMP1 as key factors. In summary, these results revealed the involvement of a well-known growth factor responsible for bone development, BMP-2, in the mechanism of oral mucosal keratinization and proliferation, and pointed out the possible downstream genes involved in this mechanism.
en-copyright=
kn-copyright=
en-aut-name=MuXindi
en-aut-sei=Mu
en-aut-mei=Xindi
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=NguyenHa Thi Thu
en-aut-sei=Nguyen
en-aut-mei=Ha Thi Thu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=WangZiyi
en-aut-sei=Wang
en-aut-mei=Ziyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=ZhaoKun
en-aut-sei=Zhao
en-aut-mei=Kun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=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=KubokiTakuo
en-aut-sei=Kuboki
en-aut-mei=Takuo
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 Molecular Biology and Biochemistry, 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=
kn-affil=Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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 Implantology, Okayama University Hospital
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=
en-keyword=cell differentiation
kn-keyword=cell differentiation
en-keyword=epithelia
kn-keyword=epithelia
en-keyword=growth factor(s)
kn-keyword=growth factor(s)
en-keyword=bioinformatics
kn-keyword=bioinformatics
en-keyword=extracellular matrix (ECM)
kn-keyword=extracellular matrix (ECM)
en-keyword=mucocutaneous disorders
kn-keyword=mucocutaneous disorders
END
start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=
article-no=
start-page=904215
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220630
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, on AAA formation and rupture.
Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE(-)(/)(-) mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS).
Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-alpha in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPAR alpha significantly attenuated the anti-oxidative effect of pemafibrate.
Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.
en-copyright=
kn-copyright=
en-aut-name=AmiokaNaofumi
en-aut-sei=Amioka
en-aut-mei=Naofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
ORCID=
en-aut-name=KondoMegumi
en-aut-sei=Kondo
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=AkagiSatoshi
en-aut-sei=Akagi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=YoshidaMasashi
en-aut-sei=Yoshida
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SaitoYukihiro
en-aut-sei=Saito
en-aut-mei=Yukihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NakamuraKazufumi
en-aut-sei=Nakamura
en-aut-mei=Kazufumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=ItoHiroshi
en-aut-sei=Ito
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=9
en-affil=Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=pemafibrate
kn-keyword=pemafibrate
en-keyword=angiotensin II
kn-keyword=angiotensin II
en-keyword=abdominal aortic aneurysm
kn-keyword=abdominal aortic aneurysm
en-keyword=oxidative stress
kn-keyword=oxidative stress
en-keyword=catalase
kn-keyword=catalase
END
start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=4930
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220323
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=LCZ696 ameliorates doxorubicin-induced cardiomyocyte toxicity in rats
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Doxorubicin (DOX)-based chemotherapy induces cardiotoxicity, which is considered the main bottleneck for its clinical application. In this study, we investigated the potential benefit of LCZ696, an angiotensin receptor-neprilysin inhibitor against DOX-induced cardiotoxicity in rats and H9c2 cells and determined whether the mechanism underlying any such effects involves its antioxidant activity. Male Sprague-Dawley rats were randomly separated into four groups, each consisting of 15 rats (DOX (1.5 mg/kg/day intraperitoneally for 10 days followed by non-treatment for 8 days); DOX + valsartan (31 mg/kg/day by gavage from day 1 to day 18); DOX + LCZ696 (68 mg/kg/day by gavage from day 1 to day 18); and control (saline intraperitoneally for 10 days). DOX-induced elevation of cardiac troponin T levels on day 18 was significantly reduced by LCZ696, but not valsartan. The DOX-induced increase in myocardial reactive oxygen species (ROS) levels determined using dihydroethidium was significantly ameliorated by LCZ696, but not valsartan, and was accompanied by the suppression of DOX-induced increase in p47phox. LCZ696 recovered the DOX-induced decrease in phosphorylation of adenosine monophosphate-activated protein kinase and increased the ratio of Bax and Bcl-2. In H9c2 cardiomyocytes, LCZ696 reduced DOX-induced mitochondrial ROS generation and improved cell viability more than valsartan. Our findings indicated that LCZ696 ameliorated DOX-induced cardiotoxicity in rat hearts in vivo and in vitro, possibly by mediating a decrease in oxidative stress.
en-copyright=
kn-copyright=
en-aut-name=MiyoshiToru
en-aut-sei=Miyoshi
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NakamuraKazufumi
en-aut-sei=Nakamura
en-aut-mei=Kazufumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=AmiokaNaofumi
en-aut-sei=Amioka
en-aut-mei=Naofumi
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=YonezawaTomoko
en-aut-sei=Yonezawa
en-aut-mei=Tomoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SaitoYukihiro
en-aut-sei=Saito
en-aut-mei=Yukihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=YoshidaMasashi
en-aut-sei=Yoshida
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=AkagiSatoshi
en-aut-sei=Akagi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=ItoHiroshi
en-aut-sei=Ito
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Pharmacology, Kindai University
kn-affil=
affil-num=5
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
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 Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
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=10
cd-vols=
no-issue=1
article-no=
start-page=6869
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200422
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Deficiency of CD44 prevents thoracic aortic dissection in a murine model
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Thoracic aortic dissection (TAD) is a life-threatening vascular disease. We showed that CD44, a widely distributed cell surface adhesion molecule, has an important role in inflammation. In this study, we examined the role of CD44 in the development of TAD. TAD was induced by the continuous infusion of beta-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, and angiotensin II (AngII) for 7 days in wild type (WT) mice and CD44 deficient (CD44(-/-)) mice. The incidence of TAD in CD44(-/-) mice was significantly reduced compared with WT mice (44% and 6%, p<0.01). Next, to evaluate the initial changes, aortic tissues at 24hours after BAPN/AngII infusion were examined. Neutrophil accumulation into thoracic aortic adventitia in CD44(-/-) mice was significantly decreased compared with that in WT mice (5.7 +/- 0.3% and 1.6 +/- 0.4%, p<0.01). In addition, BAPN/AngII induced interleukin-6, interleukin-1 beta, matrix metalloproteinase-2 and matrix metalloproteinase-9 in WT mice, all of which were significantly reduced in CD44(-/-) mice (all p<0.01). In vitro transmigration of neutrophils from CD44(-/-) mice through an endothelial monolayer was significantly decreased by 18% compared with WT mice (p<0.01). Our findings indicate that CD44 has a critical role in TAD development in association with neutrophil infiltration into adventitia.
en-copyright=
kn-copyright=
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=1
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=2
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=3
ORCID=
en-aut-name=KondoMegumi
en-aut-sei=Kondo
en-aut-mei=Megumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=AmiokaNaofumi
en-aut-sei=Amioka
en-aut-mei=Naofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=YoshidaMasashi
en-aut-sei=Yoshida
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=AkagiSatoshi
en-aut-sei=Akagi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NakamuraKazufumi
en-aut-sei=Nakamura
en-aut-mei=Kazufumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=
en-aut-name=ItoHiroshi
en-aut-sei=Ito
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=2
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=3
en-affil=Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=4
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=5
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=6
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=7
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=8
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
affil-num=9
en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University
kn-affil=
affil-num=10
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science
kn-affil=
en-keyword=Aneurysm
kn-keyword=Aneurysm
en-keyword=Aortic diseases
kn-keyword=Aortic diseases
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
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.
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=117 cd-vols= no-issue=1 article-no= start-page=17 end-page=20 dt-received= dt-revised= dt-accepted= dt-pub-year=2005 dt-pub=20050520 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=グリア境界膜に局在する新規遺伝子「リミトリン」の発見 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name= en-aut-sei= en-aut-mei= kn-aut-name=米澤朋子 kn-aut-sei=米澤 kn-aut-mei=朋子 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯学総合研究科分子医化学 en-keyword=血液脳関門 kn-keyword=血液脳関門 en-keyword=アストロサイト kn-keyword=アストロサイト en-keyword=基底膜 kn-keyword=基底膜 en-keyword=グリア境界 kn-keyword=グリア境界 en-keyword=イムノグロブリンスーパーファミリー kn-keyword=イムノグロブリンスーパーファミリー 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=2003 dt-pub=20031231 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=イムノグロブリンスーパーファミリーに属するリミトリンはアストロサイト終足が形成するグリア境界膜に局在する kn-title=Limitrin, a Novel Immunoglobulin Superpart name="family" Protein Localized to Glia Limitans Formed by Astrocyte Endfeet en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YonezawaTomoko en-aut-sei=Yonezawa en-aut-mei=Tomoko kn-aut-name=米澤朋子 kn-aut-sei=米澤 kn-aut-mei=朋子 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END