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系統識別號 U0026-0408201516501100
論文名稱(中文) Eps8 在骨重塑中所扮演的角色
論文名稱(英文) The involvement of Eps8 in bone remodeling
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 103
學期 2
出版年 104
研究生(中文) 李昌達
研究生(英文) Chang-Ta Lee
學號 s26024078
學位類別 碩士
語文別 中文
論文頁數 43頁
口試委員 指導教授-呂增宏
口試委員-馬明琪
口試委員-余冠儀
中文關鍵字 Eps8  蝕骨細胞  RANKL 
英文關鍵字 Eps8  osteoclast  RANKL 
學科別分類
中文摘要 破骨細胞是骨吸收重要的多核巨噬細胞,而多核巨噬細胞主要是由單核細胞前體細胞的細胞融合而形成的,是骨重塑必要的條件。破骨細胞的形成主要是透過 NF-κB、Src、TRAF6 和 NFATc1 的調節。而之前研究指出 Src 會和 TRAF6 結合並且活化 RANKL 的路徑。我們的實驗室之前研究也就發現,EPS8 表達在纖維細胞和上皮癌細胞會受到 Src 調控,同時 Eps8 會活化 Src 的活性。因此,我們預測 Eps8 可能也參與在破骨細胞形成的路徑當中。我們的實驗結果指出,在 RANKL 刺激下,Eps8 表達會上升。EPS8 減少則會抑制 RANKL 刺激 RAW264.7 細胞和 BMDM 形成破骨細胞。同時,我們也發現,EPS8 減少會抑制RANKL 誘導的基因表達,像是 src、 trap、nfatc-1。此外,Maf-b 是破骨細胞分化的負調控,當 Eps8 減少時 RANKL 也不會抑制 maf-b 基因的表達。由於 Src 減低並不會影響 RANKL 促進 Eps8 表達,這些結果顯示 Eps8 可能作用在 Src 的上游而參與破骨細胞的形成。
英文摘要 SUMMARY
Osteoclasts are bone-resorbing, multinucleated giant cells that are essential for bone remodeling and are formed through cell fusion of mononuclear precursor cells. Src, NF-κB, TRAF6 and NFATc1 have been implicated in osteoclastogenesis, the formation of osteoclast. Upon RANK is activated by its ligand RANKL, Src binds to TRAF6 and activates RANK-mediated signaling. Given that Eps8 expression is regulated by Src activity which in turn, activates Src in fibroblast and epithelial cancer cells, Eps8 might also involve in osteoclastogenesis. Indeed, Eps8 expression was increased in RANKL-stimulated RAW264.7 cells and BMDM. Silencing eps8 by siRNA not only reduced eps8 expression but also decreased the RANKL-induced gene expression of src, trap and nfatc-1. In addition, the expected attenuation of the negative regulator maf-b was not affected in these cells. Since Src knockdown or overexpression did not affect RANKL-induced Eps8 expression, our data strongly suggested that Eps8 might act in the upstream of Src during osteoclastogenesis.


論文目次 中文摘要……………………………………………………………………I

英文摘要……………………………………………………………………II

致謝…………………………………………………………………………VIII

目錄…………………………………………………………………………IX

圖目錄………………………………………………………………………X

縮寫檢索表…………………………………………………………………XI

緒論…………………………………………………………………………1

實驗材料及方法……………………………………………………………10

實驗結果……………………………………………………………………20

討論…………………………………………………………………………25

參考文獻……………………………………………………………………29

圖表…………………………………………………………………………34

附錄…………………………………………………………………………41







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