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  1. C100 医学部/医学系研究科
  2. C100a 雑誌掲載論文
  3. 学術雑誌

Simvastatin inhibits CD44 fragmentation in chondrocytes

http://hdl.handle.net/2237/25104
2c423e5e-e66a-4146-9691-88b30b541a39
名前 / ファイル ライセンス アクション
manuscript.pdf manuscript.pdf ファイル公開:2017/08/25 (1.0 MB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2016-11-25
タイトル
タイトル Simvastatin inhibits CD44 fragmentation in chondrocytes
著者 Terabe, Kenya

× Terabe, Kenya

WEKO 67510

Terabe, Kenya

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Takahashi, Nobunori

× Takahashi, Nobunori

WEKO 67511

Takahashi, Nobunori

Search repository
Takemoto, Toki

× Takemoto, Toki

WEKO 67512

Takemoto, Toki

Search repository
Knudson, Warren

× Knudson, Warren

WEKO 67513

Knudson, Warren

Search repository
Ishiguro, Naoki

× Ishiguro, Naoki

WEKO 67514

Ishiguro, Naoki

Search repository
Kojima, Toshihisa

× Kojima, Toshihisa

WEKO 67515

Kojima, Toshihisa

Search repository
権利
権利情報 © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
キーワード
主題Scheme Other
主題 Chondrocyte
キーワード
主題Scheme Other
主題 Pericellular matrix
キーワード
主題Scheme Other
主題 Statin
キーワード
主題Scheme Other
主題 CD44
キーワード
主題Scheme Other
主題 Lipid raft
キーワード
主題Scheme Other
主題 ADAM10
抄録
内容記述 In human osteoarthritic chondrocytes, the hyaluronan receptor CD44 undergoes proteolytic cleavage at the cell surface. CD44 cleavage is thought to require transit of CD44 into cholesterol-rich lipid rafts. The purpose of this study was to investigate whether statins exert a protective effect on articular chondrocytes due to diminution of cholesterol. Three model systems of chondrocytes were examined including human HCS-2/8 chondrosarcoma cells, human osteoarthritic chondrocytes and normal bovine articular chondrocytes. Treatment with IL-1β + Oncostatin M resulted in a substantial increase in CD44 fragmentation in each of the three chondrocyte models. Pre-incubation with simvastatin prior to treatment with IL-1β + Oncostatin M decreased the level of CD44 fragmentation, decreased the proportion of CD44 that transits into the lipid raft fractions, decreased ADAM10 activity and diminished the interaction between CD44 and ADAM10. In HCS-2/8 cells and bovine articular chondrocytes, fragmentation of CD44 was blocked by the knockdown of ADAM10. Inhibition of CD44 fragmentation by simvastatin also resulted in improved retention of pericellular matrix. Addition of cholesterol and farnesyl-pyrophosphate reversed the protective effects of simvastatin. Thus, the addition of simvastatin exerts positive effects on chondrocytes including reduced CD44 fragmentation and enhanced the retention of pericellular matrix.
内容記述タイプ Abstract
出版者
出版者 Elsevier
言語
言語 eng
資源タイプ
資源タイプresource http://purl.org/coar/resource_type/c_6501
タイプ journal article
ISSN
収録物識別子タイプ ISSN
収録物識別子 0003-9861
書誌情報 Archives of Biochemistry and Biophysics

巻 604, p. 1-10, 発行日 2016-08-25
著者版フラグ
値 author
URI
識別子 http://doi.org/10.1016/j.abb.2016.05.019
識別子タイプ DOI
URI
識別子 http://hdl.handle.net/2237/25104
識別子タイプ HDL
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