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著作: [浜田 大輔]/Maynard R/Schott E/Drinkwater CJ/Ketz JP/Kates SL/Jonason JH/Hilton MJ/Zuscik MJ/Mooney RA/Suppressive effects of insulin on tumor necrosis factor-dependent early osteoarthritic changes associated with obesity and type 2 diabetes mellitus/[Arthritis & Rheumatology]

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EID
319383
EOID
939690
Map
0
LastModified
2019年3月2日(土) 20:41:44
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浜田 大輔
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨
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組織 推奨
著者 必須
  1. 浜田 大輔([徳島大学.大学院医歯薬学研究部.医学域.先端医学教育研究プロジェクト]/[徳島大学.大学院医歯薬学研究部.医学域.医科学部門.外科系.運動機能外科学]/[徳島大学.病院.診療科.感覚·皮膚·運動機能科.整形外科])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. (英) Maynard R
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    学籍番号 推奨
  3. (英) Schott E
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    学籍番号 推奨
  4. (英) Drinkwater CJ
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    貢献度 任意
    学籍番号 推奨
  5. (英) Ketz JP
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    貢献度 任意
    学籍番号 推奨
  6. (英) Kates SL
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    貢献度 任意
    学籍番号 推奨
  7. (英) Jonason JH
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    貢献度 任意
    学籍番号 推奨
  8. (英) Hilton MJ
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    貢献度 任意
    学籍番号 推奨
  9. (英) Zuscik MJ
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    学籍番号 推奨
  10. (英) Mooney RA
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    学籍番号 推奨
題名 必須

(英) Suppressive effects of insulin on tumor necrosis factor-dependent early osteoarthritic changes associated with obesity and type 2 diabetes mellitus

副題 任意
要約 任意

(英) Obesity is a state of chronic inflammation that is associated with insulin resistance and type 2 diabetes mellitus (DM), as well as an increased risk of osteoarthritis (OA). This study was undertaken to define the links between obesity-associated inflammation, insulin resistance, and OA, by testing the hypotheses that 1) tumor necrosis factor (TNF) is critical in mediating these pathologic changes in OA, and 2) insulin has direct effects on the synovial joint that are compromised by insulin resistance. The effects of TNF and insulin on catabolic gene expression were determined in fibroblast-like synoviocytes (FLS) isolated from human OA synovium. Synovial TNF expression and OA progression were examined in 2 mouse models, high-fat (HF) diet-fed obese mice with type 2 DM and TNF-knockout mice. Insulin resistance was investigated in synovium from patients with type 2 DM. Insulin receptors (IRs) were abundant in both mouse and human synovial membranes. Human OA FLS were insulin responsive, as indicated by the dose-dependent phosphorylation of IRs and Akt. In cultures of human OA FLS with exogenous TNF, the expression and release of MMP1, MMP13, and ADAMTS4 by FLS were markedly increased, whereas after treatment with insulin, these effects were selectively inhibited by >50%. The expression of TNF and its abundance in the synovium were elevated in samples from obese mice with type 2 DM. In TNF-knockout mice, increases in osteophyte formation and synovial hyperplasia associated with the HF diet were blunted. The synovium from OA patients with type 2 DM contained markedly more macrophages and showed elevated TNF levels as compared to the synovium from OA patients without diabetes. Moreover, insulin-dependent phosphorylation of IRs and Akt was blunted in cultures of OA FLS from patients with type 2 DM. TNF appears to be involved in mediating the advanced progression of OA seen in type 2 DM. While insulin plays a protective, antiinflammatory role in the synovium, insulin resistance in patients with type 2 DM may impair this protective effect and promote the progression of OA.

キーワード 推奨
発行所 推奨
誌名 必須 Arthritis & Rheumatology(American College of Rheumatology)
(pISSN: 2326-5191, eISSN: 2326-5205)
ISSN 任意 2326-5205
ISSN: 2326-5191 (pISSN: 2326-5191, eISSN: 2326-5205)
Title: Arthritis & rheumatology (Hoboken, N.J.)
Title(ISO): Arthritis Rheumatol
Supplier: American College of Rheumatology
Publisher: Wiley Publishing
 (NLM Catalog  (Wiley  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 68
必須 6
必須 1392 1402
都市 任意
年月日 必須 2016年 6月 末日
URL 任意
DOI 任意 10.1002/art.39561    (→Scopusで検索)
PMID 任意 26713606    (→Scopusで検索)
NAID 任意
WOS 任意 000383493600013
Scopus 任意 2-s2.0-84971328569
機関リポジトリ 113028
評価値 任意
被引用数 任意
指導教員 推奨
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  1. (英) Article.ELocationID: 10.1002/art.39561

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) OtherID: NIHMS746368

  4. (英) OtherID: PMC4882234