Smad3 Deficiency Leads to Mandibular Condyle Degradation via the Sphingosine 1-Phosphate (S1P)/S1P3 Signaling Axis

• 資料種別: 博士論文
• タイトル: Smad3 Deficiency Leads to Mandibular Condyle Degradation via the Sphingosine 1-Phosphate (S1P)/S1P3 Signaling Axis
• 著者・編者: Mori, Hiroki; Izawa, Takashi; Tanaka, Eiji
• 著者標目: Mori, Hiroki; Izawa, Takashi; Tanaka, Eiji
• 出版事項: American Society for Investigative Pathology|Elsevier
• 出版年月日等: 2015-08-10
• 出版年（W3CDTF）: 2015-08-10
• 並列タイトル等: Smad3の欠損はS1P/S1P3シグナル経路を介して下顎頭軟骨変性を生じる; Chondrocyte Migration Mediated by Smad3/S1P3
• タイトル（掲載誌）: The American Journal of Pathology
• 巻号年月日等（掲載誌）: 185 10
• 掲載巻: 185
• 掲載号: 10
• 掲載ページ: 2742-2756
• ISSN（掲載誌）: ISSN : 0002-9440
• 授与機関名: 徳島大学
• 授与年月日: 2016-03-23
• 報告番号: 甲第2940号
• 学位: 博士（歯学）
• 本文の言語コード: eng
• 件名標目: TMJ-OA; Smad3; S1P; migration; S1P3
• 対象利用者: 一般
• 一般注記: Temporomandibular joint osteoarthritis is a degenerative disease that is characterized by permanent cartilage destruction. Transforming growth factor (TGF)-β is one of the most abundant cytokines in the bone matrix and is shown to regulate the migration of osteoprogenitor cells. It is hypothesized that TGF-β/Smad3 signaling affects cartilage homeostasis by influencing sphingosine 1-phosphate (S1P)/ S1P receptor signaling and chondrocyte migration. We therefore investigated the molecular mechanisms by which crosstalk may occur between TGF-β/Smad3 and S1P/S1P receptor signaling to maintain condylar cartilage and to prevent temporomandibular joint osteoarthritis. Abnormalities in the condylar subchondral bone, including dynamic changes in bone mineral density and microstructure, were observed in Smad3-/- mice by microcomputed tomography. Cell-free regions and proteoglycan loss characterized the cartilage degradation present, and increased numbers of apoptotic chondrocytes and matrix metalloproteinase 13+ chondrocytes were also detected. Furthermore, expression of S1P receptor 3 (S1P3), but not S1P1 or S1P2, was significantly down-regulated in the condylar cartilage of Smad3-/- mice. By using RNA interference technology and pharmacologic tools, S1P was found to transactivate Smad3 in an S1P3/TGF-β type II receptor-dependent manner, and S1P3 was found to be required for TGF-β-induced migration of chondrocyte cells and downstream signal transduction via Rac1, RhoA, and Cdc42. Taken together, these results indicate that the Smad3/S1P3 signaling pathway plays an important role in the pathogenesis of temporomandibular joint osteoarthritis.
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.1016/j.ajpath.2015.06.015
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 徳島大学 : 徳島大学機関リポジトリ

目次

https://repo.lib.tokushima-u.ac.jp/files/public/10/109705/20170929143806673662/LID201606141004.pdf fulltext

https://repo.lib.tokushima-u.ac.jp/files/public/10/109705/20170929143807292158/LID201606141005.pdf fulltext

https://repo.lib.tokushima-u.ac.jp/files/public/10/109705/20190531155152756521/k2940_fulltext.pdf fulltext