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タイトル: | A VCP modulator, KUS121, as a promising therapeutic agent for post-traumatic osteoarthritis |
著者: | Saito, Motoo Nishitani, Kohei https://orcid.org/0000-0002-8327-3826 (unconfirmed) Ikeda, Hanako O. Yoshida, Shigeo Iwai, Sachiko Ji, Xiang Nakahata, Akihiro Ito, Akira https://orcid.org/0000-0002-9645-9777 (unconfirmed) Nakamura, Shinichiro Kuriyama, Shinichi Yoshitomi, Hiroyuki https://orcid.org/0000-0001-7339-9030 (unconfirmed) Murata, Koichi Aoyama, Tomoki Ito, Hiromu Kuroki, Hiroshi Kakizuka, Akira Matsuda, Shuichi |
著者名の別形: | 斉藤, 元央 西谷, 江平 池田, 華子 吉田, 繁央 岩井, 祥子 季, 翔 中畑, 晶博 伊藤, 明良 中村, 伸一郎 栗山, 新一 吉富, 啓之 村田, 浩一 青山, 朋樹 伊藤, 宣 黒木, 裕士 垣塚, 彰 松田, 秀一 |
キーワード: | Musculoskeletal system Rheumatology |
発行日: | 27-Nov-2020 |
出版者: | Springer Nature |
誌名: | Scientific Reports |
巻: | 10 |
論文番号: | 20787 |
抄録: | Post-traumatic osteoarthritis (PTOA) is a major cause which hinders patients from the recovery after intra-articular injuries or surgeries. Currently, no effective treatment is available. In this study, we showed that inhibition of the acute stage chondrocyte death is a promising strategy to mitigate the development of PTOA. Namely, we examined efficacies of Kyoto University Substance (KUS) 121, a valosin-containing protein modulator, for PTOA as well as its therapeutic mechanisms. In vivo, in a rat PTOA model by cyclic compressive loading, intra-articular treatments of KUS121 significantly improved the modified Mankin scores and reduced damaged-cartilage volumes, as compared to vehicle treatment. Moreover, KUS121 markedly reduced the numbers of TUNEL-, CHOP-, MMP-13-, and ADAMTS-5-positive chondrocytes in the damaged knees. In vitro, KUS121 rescued human articular chondrocytes from tunicamycin-induced cell death, in both monolayer culture and cartilage explants. It also significantly downregulated the protein or gene expression of ER stress markers, proinflammatory cytokines, and extracellular-matrix-degrading enzymes induced by tunicamycin or IL-1β. Collectively, these results demonstrated that KUS121 protected chondrocytes from cell death through the inhibition of excessive ER stress. Therefore, KUS121 would be a new, promising therapeutic agent with a protective effect on the progression of PTOA. |
記述: | 京大開発の薬剤「KUS121」の変形性膝関節症への効果を確認 --外傷性変形性関節症の治療薬として臨床応用へ--. 京都大学プレスリリース. 2020-12-17. |
著作権等: | © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
URI: | http://hdl.handle.net/2433/259824 |
DOI(出版社版): | 10.1038/s41598-020-77735-2 |
PubMed ID: | 33247195 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2020-12-17-1 |
出現コレクション: | 学術雑誌掲載論文等 |
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