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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
著者
森, 浩喜 徳島大学大学院口腔科学教育部(口腔科学専攻) 徳島大学 教育研究者総覧 KAKEN研究者をさがす
キーワード
TMJ-OA
Smad3
S1P
migration
S1P3
資料タイプ
学位論文
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.
掲載誌名
The American Journal of Pathology
ISSN
00029440
cat書誌ID
AA00520990
AA12024839
出版者
American Society for Investigative Pathology|Elsevier
185
10
開始ページ
2742
終了ページ
2756
発行日
2015-08-10
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
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2940号
学位記番号
甲口第405号
学位授与年月日
2016-03-23
学位名
博士(歯学)
学位授与機関
徳島大学
部局
病院
歯学系