中草藥促進成骨細胞分化和抑制腫瘤誘導骨溶蝕之作用機制探討(新制多年期第2年)

CNU IR > Pharmacy and Science > Dept. of Biotechnology (including master's program) > MOST Project > Item 310902800/22422

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Title:	中草藥促進成骨細胞分化和抑制腫瘤誘導骨溶蝕之作用機制探討(新制多年期第2年) The Effect of Chinese Herbal Medicines on the Induction of Osteoblastic Differentiation and the Inhibition of Cancer-Induced Osteoclastogenesis
Authors:	張竣凱
Contributors:	生物科技系(所)
Date:	2009
Issue Date:	2010-03-26 15:34:11 (UTC+8)
Publisher:	台南縣：嘉南藥理科技大學生物科技系(所)
Abstract:	骨質疏鬆（Osteoporosis）是由於骨形成(bone resorption)和骨吸收(bone formation)的不平衡而導致骨密度減少，而體內骨的平衡取則決於成骨細胞(osteoblast)和蝕骨細胞(osteoclast)相互作用。我們之前已證實屬於香豆素衍生物的歐前胡素(imperatorin)它能直接有效的誘導成骨細胞分化。本研究第二年進度在探討imperatorin是否透過BMP和MAPK的訊息途徑，誘導MG-63細胞分化作用，著重於MAPK 訊息途徑與BMP 或Smad 的關係性，評估imperatorin抗骨質疏鬆症活性的分子機轉。今以RT-PCR証實Imperatorin使MG-63細胞的BMP相關基因表現（包括BMP-4、BMP-7、Smad-1、Smad-5、Runx2、ALP、OCN等）向上調控。在western blotting實驗證實1 uM Imperatorin可使細胞中的MAPK轉變成磷酸化的活化形式。此外，16 uM Imperatorin處理組可使MAPK路徑相關的SAPK/JNK及p38蛋白質含量增加，呈現向上調控的情形。所以MAPK 訊息傳遞路徑也可能參與Imperatorin促進MG63細胞成骨分化作用。基質金屬蛋白酶MMP可以分解胞外基質中的蛋白質成分，造成胞外基質的瓦解。以gelatin zymography 分析MMP蛋白質的活性，結果各處理組皆有MMP蛋白質的活性出現，其中1 μM處理組的活性較強。目前Imperatorin處理12 day後的MG63細胞有類似礦化結節作用，但此現象能需再次證實。本研究推論屬於香豆素衍生物imperatorin可以透過BMP及MAPK之訊息傳遞路徑活化MG-63細胞分化作用。 Osteoporosis is caused by the imbalance of the bone resorption and the bone formation that further leads to the reduction of the bone mineral density. In our previous study, we have approved the ability of imperatorin of the coumarin derivatives to directly induce the differentiation of the osteoblast. To clarify whether the imperatorin involves in the induction of the differentiation of the MG-63 cells via the BMP and MAPK pathway or not, the present study will focus on the evaluation of the relationship of the MAPK pathway and the BMP and/or the Smad so as to elucidate the molecular action of the imperatorin in the mechanism of anti-osteoporosis. Through the RT-PCR determination, we have approved that the imperatorin can upregulate the expressions of certain genes associated with the MG-63 cells, such as BMP-4, BMP-7, Smad-1, Smad-5, Runx2, ALP, and OCN. Western blot analysis further showed the active, phosphorylated form of MAPK can be effectively induced by 1 uM of Imperatorin. In addition, the increased figure of the protein expressions of the SAPK/JNK and the p38, both associated with the MAPK pathway, was observed when the cells have been treated with the 16 uM of the imperatorin. These results showed the MAPK pathway may enhance the differentiation of the MG63 cells towards the osteoblasts. The matrix metalloproteinases (MMPs) are capable of lysing the extracellular matrix protein to break down the extracellular matrix. The activity of the MMP was analyzed by gelatin zymography. As showed in the results, all test groups revealed the MMP protein activity, and particularly, in which, the test group with the treatment of the 1 μM of the imperatorin possessed a higher MMP activity in compared with that of others. The expression of mineralization nodule was showed after the MG63 cells were treated with the Imperatorin for 12 days. However, this result needs to be reconfirmed. At this moment, our study has showed the imperatorin of the coumarin derivatives is capable of activating the differentiation of the MG63 cells through the BMP and MAPK signal transduction pathway.
Relation:	計畫編號：NSC98-2221-E041-012 計畫年度： 98 ；執行起迄： 2009-08-01～2010-07-31 核定總金額：3,069,000元,98年度核定金額：1,023,000元
Appears in Collections:	[Dept. of Biotechnology (including master's program)] MOST Project

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