ID | 109705 |
タイトル別表記 | 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
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著者 | |
キーワード | TMJ-OA
Smad3
S1P
migration
S1P3
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資料タイプ |
学位論文
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抄録 | 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.
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掲載誌名 |
The American Journal of Pathology
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ISSN | 00029440
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cat書誌ID | AA00520990
AA12024839
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出版者 | American Society for Investigative Pathology|Elsevier
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巻 | 185
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号 | 10
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開始ページ | 2742
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終了ページ | 2756
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発行日 | 2015-08-10
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備考 | 内容要旨・審査要旨・論文本文の公開:
内容要旨 : LID201606141004.pdf 審査要旨 : LID201606141005.pdf 論文全文 : k2940_fulltext.pdf 著者の申請により要約(2016-06-15公開)に替えて論文全文を公開(2019-06-05) 本論文は, 著者Hiroki Moriの学位論文として提出され, 学位審査・授与の対象となっている。 |
EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
博士論文全文を含む
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文科省報告番号 | 甲第2940号
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学位記番号 | 甲口第405号
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学位授与年月日 | 2016-03-23
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学位名 |
博士(歯学)
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学位授与機関 |
徳島大学
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部局 |
病院
歯学系
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