- 學位論文
運用MMP-3啟動子-報導基因之基因轉殖大鼠探討矯正牙齒移動與關節炎之相互關係
Study of Interaction of Orthodontic Tooth Movement and Arthritis using a MMP-3 Promoter-Reporter Transgenic Rat Model
摘要
矯正牙齒移動對於牙周韌帶的壓力與張力會連帶影響周邊神經、血管，吸引發炎因子聚集及釋放，引起發炎反應，促進組織重塑，這些發炎因子也同時在免疫系統及骨系統中扮演重要角色，因此想研究矯正牙齒移動引發的局部發炎反應對全身系統性的影響，而全身性的發炎反應是否影響局部。 本實驗使用MMP-3 promoter-Luciferase-GFP之基因轉殖大鼠模型，施以矯正牙齒移動或/與膠原蛋白誘發關節炎，以非侵入式活體分子影像系統 (In vivo imaging system, IVIS) 觀察MMP-3啟動子轉錄的報導基因冷光酶訊號，採血偵測細胞激素的表現，並在犧牲後照射顯微電腦斷層影像(micro CT image)量測牙齒移動距離、分析骨體積比率。矯正牙齒移動組實驗為期14天；誘發關節炎組實驗為期21天。實驗發現口內的冷光訊號實驗組皆大於對照組，而且合併誘發關節炎及矯正牙齒移動的組別也比單純矯正牙齒移動的組別訊號高，訊號皆在放置彈簧後一天顯著上升，之後降低；牙齒移動距離、骨體積比率方面，實驗組也大於對照組。由抽血數值整體看起來，第21天的誘發關節炎組有大於合併誘發關節炎及矯正牙齒移動組的趨勢。 本研究顯示在全身性發炎環境下，並不會顯著影響局部矯正牙齒移動的距離及骨代謝，但抽血數值較無一致性，沒有看到因局部發炎，引起血流中發炎因子濃度上升的趨勢。
並列摘要
In response to pressure and tension force from the periodontal ligament during orthodontic tooth movement, many inflammatory molecules are produced and released from the peripheral nerve and vessels and then stimulate tissue remodeling. These inflammatory molecules play an important role in both the immune and bone system. Therefore, we planned to investigate whether any systemic inflammation gets more severe by regional orthodontic tooth movement, and whether the systemic inflammation influence the local response. In our study, we used MMP-3 promoter-Luciferase-GFP transgenic rat model for orthodontic tooth movement (OTM) or/and collagen-induced arthritis (CIA). In vivo imaging system (IVIS) was used to detect luciferase signal from MMP-3 promoter, and cytokine levels were measured by blood samples. In the end, we utilized micro-CT image to measure the distance of tooth movement and bone volume fraction. The experiment was 14-day span in the OTM group, and 21-day span in the CIA group. Signal from the experimental side of the mouth was increased in the experimental group than the control group. Moreover, we found that it was significantly elevated one day after spring placement in all groups. Distance of tooth movement and bone volume fraction were also larger in experimental group than the control group. From the level of inflammatory factors in the blood sample in the 21th day, most of the level in the CIA group were higher than CIA combined with OTM group. In this study, we demonstrated that the distance of tooth movement and localized bone metabolism were not significantly influenced by CIA, a systemic inflammation. Moreover, localized inflammation of OTM did not change the concentrations of measured molecules in the bloodstream in CIA.