ID | 66678 |
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Author |
Hotta, Yoshifumi
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yoshida, Aki
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nasu, Yoshihisa
Department of Orthopaedic Surgery, Okayama University Hospital
Nakahara, Ryuichi
Department of Orthopaedic Surgery, Okayama University Hospital
Naniwa, Shuichi
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Shimizu, Noriyuki
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ichikawa, Chinatsu
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Lin, Deting
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ozaki, Toshifumi
Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Abstract | We investigated the effects of a Tankyrase (TNKS-1/2) inhibitor on mechanical stress-induced gene expression in human chondrocytes and examined TNKS-1/2 expression in human osteoarthritis (OA) cartilage. Cells were seeded onto stretch chambers and incubated with or without a TNKS-1/2 inhibitor (XAV939) for 12 h. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 8% elongation, 30 min) was applied and the gene expression of type II collagen a1 chain (COL2A1), aggrecan (ACAN), SRY-box9 (SOX9), TNKS-1/2, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and matrix metalloproteinase-13 (MMP-13) were examined by real-time PCR. The expression of ADAMTS-5, MMP-13, nuclear translocation of nuclear factor-κB (NF-κB), and β-catenin were examined by immunocytochemistry and Western blotting. The concentration of IL-1β in the supernatant was examined by enzyme-linked immunosorbent assay (ELISA). TNKS-1/2 expression was assessed by immunohistochemistry in human OA cartilage obtained at the total knee arthroplasty. TNKS-1/2 expression was increased after CTS. The expression of anabolic factors were decreased by CTS, however, these declines were abrogated by XAV939. XAV939 suppressed the CTS-induced expression of catabolic factors, the release of IL-1β, as well as the nuclear translocation of NF-κB and β-catenin. TNKS-1/2 expression increased in mild and moderate OA cartilage. Our results demonstrated that XAV939 suppressed mechanical stress-induced expression of catabolic proteases by the inhibition of NF-κB and activation of β-catenin, indicating that TNKS-1/2 expression might be associated with OA pathogenesis.
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Keywords | osteoarthritis
chondrocyte
mechanical stress
tankyrases
XAV939
SOX9
ADAMTS-5
MMP-13
IL-1β
NF-κB
β-catenin
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Published Date | 2024-01-24
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Publication Title |
International Journal of Molecular Sciences
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Volume | volume25
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Issue | issue3
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Publisher | MDPI
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Start Page | 1443
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ISSN | 1661-6596
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2024 by the authors.
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File Version | publisher
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PubMed ID | |
DOI | |
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Related Url | isVersionOf https://doi.org/10.3390/ijms25031443
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License | https://creativecommons.org/licenses/by/4.0/
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Citation | Hotta, Y.; Nishida, K.; Yoshida, A.; Nasu, Y.; Nakahara, R.; Naniwa, S.; Shimizu, N.; Ichikawa, C.; Lin, D.; Fujiwara, T.; et al. Inhibitory Effect of a Tankyrase Inhibitor on Mechanical Stress-Induced Protease Expression in Human Articular Chondrocytes. Int. J. Mol. Sci. 2024, 25, 1443. https://doi.org/10.3390/ijms25031443
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Funder Name |
Eisai Co., Ltd.
AbbVie GK
Mitsubishi Tanabe Pharma Corp.
Chugai Pharmaceutical Co., Ltd.
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助成番号 | HHCS20200815003
2218
MTPS20200621008
AC-1-20210606161839-093201
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