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研究生:楊智彰
研究生(外文):Chih-Chang Yang
論文名稱:人類膝退化性關節炎翳狀組織之細胞胞外基質降解酵素分析
論文名稱(外文):Analysis of extracellular matrix degradation enzymes in human knee osteoarthritis pannus tissue
指導教授:王懷詩
指導教授(外文):Hwai-Shi Wang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:解剖暨細胞生物學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:29
中文關鍵詞:退化性關節炎基質金屬蛋白酶血管內皮成長因子血管內皮成長因子受體2型缺氧誘導因子1-α基質金屬蛋白酶抑制因子
外文關鍵詞:osteoarthritisMMPsADAMTS-4VEGFVEGFR-2HIF-1α
相關次數:
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中文摘要
研究目的: 退化性關節炎與軟骨的瓦解息息相關,本研究企圖闡明人類膝退化性關節炎患者關節面上的翳狀組織具有哪些軟骨細胞胞外基質瓦解酵素及是否有這些酵素的活化因子-血管內皮成長因子,或是具有血管內皮成長因子的轉錄因子-缺氧誘導因子1α的表現?

研究設計:退化性關節炎的翳狀病理組織採取自20 個來自膝關節內視鏡或全膝關節置換術的退化性關節炎患者。基質金屬蛋白酶9、10、15、16和ADAMTS-4, 基質金屬蛋白酶抑制因子1,2、 低氧誘導因子1-α、血管內皮生長因子和血管內皮生長因子受體2型等的表現,利用即時定量聚合酶連鎖反應、免疫沉澱法、及螢光組織免疫染色等實驗來進行偵測。

結果:從及時定量聚合酶連鎖反應、免疫沉澱法、及螢光組織免疫染色的實驗結果顯示,基質金屬蛋白酶9、10、15、16和ADAMTS-4,、 低氧誘導因子1-α、血管內皮生長因子和血管內皮生長因子受體2型等的表現皆高於正常人類滑膜成纖維細胞,然而基質金屬蛋白酶抑制因子1,2的表現則低於正常人類滑膜成纖維細胞。

討論:從我們的研究發現到,基質金屬蛋白酶9、10、15、16和ADAMTS-4, 基質金屬蛋白酶抑制因子1,2、 低氧誘導因子1-α、血管內皮生長因子和血管內皮生長因子受體2型在退化性關節炎翳狀組織上具有意義的表現量,提示這些酵素與因子也許參與了退化性關節炎中,翳狀組織的侵入或軟骨瓦解的作用。
Summary
Objective: The osteoarthritis (OA) is directly correlated with cartilage degradation. This study investigated the expression of extracellular matrix (ECM) degrading enzymes, VEGF (an activator of ECM degrading enzymes), and HIF-1α (a transcriptional activator of VEGF) on pannus of osteoarthritis patients.

Design: Pannus specimens were obtained from 20 knee joints with OA undergoing arthroscopic surgery or total knee replacement. The expression of MMP-9, -10, -15, -16, ADAMTS-4, TIMP-1, -2, VEGF, VEGFR-2 and HIF-1α were assessed by quantitative real-time PCR, IP western blotting and immunofluorescence staining.

Results: By immunofluorescence staining, MMP-9, -10, -15, -16, ADAMTS-4, TIMP-1, -2, VEGF, VEGFR-2 and HIF-1α were seen to be expressed in pannus of OA patients. Compared to normal human fibroblast-like synoviocytes, the mRNA and protein expression of MMP-9, -10, -15, -16, ADAMTS-4, VEGF, VEGFR-2 and HIF-1α were higher in pannus of OA patients, while TIMP-1, -2 were lower in pannus.

Conclusion: Pannus in OA patients expressed significant amount of MMP-9, -10, -15, -16, ADAMTS-4, TIMP-1, -2, VEGF, VEGFR-2 and HIF-1α, which suggests that these enzymes and factors may be involved in pannus invasion or cartilage degradation.

Key words: OA, MMPs, Pannus, ADAMTS-4, VEGF, VEGFR-2, ADAMTS-4, TIMP-1, TIMP-2, HIF-1α
Contents

Signature Page i
Thesis Approval Form ii
Acknowledgments iii iv
Chinese summary vi
English summary v
Abbreviations vi
Introduction 1
Materials and methods 3
Pannus samples 4
Cell culture 4
Immunofluorescence and Histochemical analyses 4
Quantitative real-time PCR assays 4
Immunoprecipitation 5
Stastiscal analyses 6
Results 7
Expression of HIF-1α in OA pannus tissues 7
Expression of VEGF and VEGFR-2 in OA pannus tissues 7
Expression of MMP-9, MMP-10, MMP-15, MMP-16, ADAMTS-4, TIMP-1 and TIMP-2 in OA pannus tissues 7
Discussion 8
References 10
Figures, Appendices and Supplementary data 13
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