本文選題：骨質(zhì)疏松　切入點(diǎn)：利拉魯肽　出處：《河北醫(yī)科大學(xué)》2017年博士論文

【摘要】：胰高血糖素樣肽-1(glucagon-like peptide 1,GLP-1)是腸道L型細(xì)胞分泌的一種腸促胰島素,主要的生理學(xué)作用包括進(jìn)食后呈葡萄糖依賴(lài)性刺激胰島素的分泌和釋放,促進(jìn)胰腺β細(xì)胞的增殖并抑制其凋亡,抑制胰高血糖素分泌,抑制胃排空,促進(jìn)飽食感產(chǎn)生等。但GLP-1在體內(nèi)容易被二肽基肽酶Ⅳ(dipeptidyl peptidase-Ⅳ,DPP-Ⅳ)降解,穩(wěn)定性差,無(wú)法應(yīng)用于臨床,因此科研人員研發(fā)了多種GLP-1類(lèi)似物。利拉魯肽與人GLP-1有97%同源,半衰期約12~14小時(shí);Exendin-4與哺乳動(dòng)物GLP-1的氨基酸序列53%同源,為含有39個(gè)氨基酸的多肽,注射后2小時(shí)就可到達(dá)血藥濃度峰值。由于利拉魯肽和Exendin-4都不會(huì)被體內(nèi)的DPP-Ⅳ降解,因此兩者既克服了天然GLP-1易被降解的缺點(diǎn),又保留了GLP-1的各種生理作用和治療優(yōu)勢(shì)。利拉魯肽和Exendin-4是目前臨床上常用的降糖藥,不僅可以控制血糖,還可通過(guò)多種途徑影響骨代謝。Zhan等研究發(fā)現(xiàn),GLP-1可以抑制Runt相關(guān)轉(zhuǎn)錄因子2(runt-related transcription factor2,Runx2)的產(chǎn)生進(jìn)而抑制小鼠血管平滑肌細(xì)胞的成骨分化。然而,多數(shù)體外研究證實(shí),GLP-1可以促進(jìn)成骨分化的發(fā)生。因此,GLP-1及其類(lèi)似物到底是抑制還是促進(jìn)成骨分化尚未定論。Smads是轉(zhuǎn)化生長(zhǎng)因子-β(transforming growth factor-β,TGF-β)的信號(hào)轉(zhuǎn)導(dǎo)和調(diào)節(jié)分子。已證實(shí)Wnt/β-catenin和磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)信號(hào)通路均可調(diào)節(jié)Smad2和Smad3的活性和核轉(zhuǎn)移,并參與成骨分化過(guò)程。此外,Hedgehog也是影響細(xì)胞分化的重要信號(hào)通路,Hedgehog信號(hào)可使骨髓間充質(zhì)干細(xì)胞選擇性向成骨細(xì)胞分化。為闡述胰高血糖素樣肽-1類(lèi)似物促進(jìn)前成骨細(xì)胞的成骨分化及其機(jī)制,本研究分四部分:第一部分利拉魯肽促進(jìn)前成骨細(xì)胞向成骨分化;第二部分利拉魯肽對(duì)前成骨細(xì)胞向成骨分化影響的信號(hào)通路研究;第三部分Exendin-4促進(jìn)前成骨細(xì)胞向成骨分化;第四部分Exendin-4對(duì)前成骨細(xì)胞向成骨分化影響的信號(hào)通路研究。第一部分利拉魯肽促進(jìn)前成骨細(xì)胞向成骨分化目的:明確不同濃度利拉魯肽對(duì)小鼠成樣骨細(xì)胞mc3t3-e1增殖和分化的影響。方法:1將體外培養(yǎng)的小鼠成樣骨細(xì)胞mc3t3-e1分為對(duì)照組和干預(yù)組(10-9mol/l利拉魯肽,10-8mol/l利拉魯肽,10-7mol/l利拉魯肽),接種細(xì)胞后第24、48和72h對(duì)細(xì)胞進(jìn)行ckk-8檢測(cè)并利用流式細(xì)胞術(shù)進(jìn)行細(xì)胞周期檢測(cè)。2將普通培養(yǎng)液中培養(yǎng)的mc3t3-e1細(xì)胞設(shè)置為空白對(duì)照組,成骨培養(yǎng)液中培養(yǎng)的mc3t3-e1細(xì)胞設(shè)置為成骨對(duì)照組,成骨干預(yù)組中利拉魯肽濃度分別設(shè)為10-9mol/l、10-8mol/l和10-7mol/l。不同濃度利拉魯肽干預(yù)細(xì)胞48h后進(jìn)行免疫熒光染色定位細(xì)胞glp-1受體(glucagon-likepeptide1receptor,glp-1r)的表達(dá)部位;分別取第3、7、14和21天的細(xì)胞進(jìn)行堿性磷酸酶(alkalinephosphatase,alp)活性測(cè)定和茜素紅染色半定量測(cè)定;利用westernblot分析和real-timert-pcr檢測(cè)檢測(cè)細(xì)胞glp-1r、runx2和骨鈣素(osteocalcin,ocn)的mrna水平和蛋白表達(dá)。結(jié)果:1利拉魯肽對(duì)mc3t3-e1細(xì)胞的細(xì)胞活力和細(xì)胞周期均無(wú)顯著影響。2mc3t3-e1細(xì)胞的細(xì)胞質(zhì)與細(xì)胞核中均存在glp-1r,利拉魯肽可以增加成骨培養(yǎng)基中mc3t3-e1細(xì)胞glp-1r的表達(dá),并具有劑量依賴(lài)性;在成骨培養(yǎng)基中加入10-7mol/l利拉魯肽后,14天時(shí)glp-1r表達(dá)增加最明顯。3利拉魯肽可劑量依賴(lài)性促進(jìn)mc3t3-e1細(xì)胞向成骨細(xì)胞分化時(shí)的alp活性和鈣沉積量。4利拉魯肽上調(diào)runx2和ocn的mrna水平和蛋白表達(dá),并具有劑量依賴(lài)性;runx2的mrna水平和蛋白表達(dá)在7天達(dá)到峰值,ocn的mrna水平和蛋白表達(dá)在21天達(dá)到峰值。第二部分利拉魯肽對(duì)前成骨細(xì)胞向成骨分化影響的信號(hào)通路研究目的:探索smad2和smad3是否參與了利拉魯肽促進(jìn)小鼠成樣骨細(xì)胞mc3t3-e1向成骨分化的過(guò)程,并進(jìn)一步明確利拉魯肽是否通過(guò)wnt/β-catenin信號(hào)通路和pi3k-akt信號(hào)通路調(diào)節(jié)smad2和smad3的轉(zhuǎn)錄和蛋白表達(dá)。方法:1將普通培養(yǎng)液中培養(yǎng)的mc3t3-e1細(xì)胞設(shè)置為空白對(duì)照組,成骨培養(yǎng)液中培養(yǎng)的mc3t3-e1細(xì)胞設(shè)置為成骨對(duì)照組,成骨干預(yù)組中利拉魯肽濃度分別設(shè)為10-9mol/l、10-8mol/l和10-7mol/l。利用real-timert-pcr檢測(cè)細(xì)胞smad2和smad3的基因表達(dá)水平,用westernblot分析技術(shù)檢測(cè)p-smad2、smad2、p-smad3和smad3蛋白表達(dá)水平。2體外培養(yǎng)小鼠前成樣骨細(xì)胞mc3t3-e1,經(jīng)小干擾rna(smallinterferingrna,sirna)轉(zhuǎn)染以沉默smad2和smad3基因表達(dá)。取成骨誘導(dǎo)培養(yǎng)條件下的mc3t3-e1細(xì)胞隨機(jī)分為8組,分別為空白對(duì)照組、空載體組、空載體+利拉魯肽組、smad2-sirna組、sismad2+利拉魯肽組、smad3-sirna組和sismad3+利拉魯肽組。利用real-timert-pcr檢測(cè)細(xì)胞smad2、smad3和runx2的基因表達(dá)水平,用westernblot分析技術(shù)檢測(cè)p-smad2、smad2、p-smad3、smad3和runx2的蛋白表達(dá)水平,并通過(guò)檢測(cè)alp活性和茜素紅染色及半定量法評(píng)價(jià)細(xì)胞的分化程度。2我們進(jìn)一步應(yīng)用了wnt/β-catenin信號(hào)通路抑制劑dkk-1和pi3k-akt信號(hào)通路抑制劑ly294002以確定wnt/β-catenin信號(hào)通路和pi3k-akt信號(hào)通路在利拉魯肽對(duì)smad2和smad3影響中的作用。結(jié)果:1利拉魯肽上調(diào)smad2和smad3的mrna水平,并具有劑量反應(yīng)關(guān)系。2利拉魯肽可以增加p-smad2、smad2、p-smad2/smad2、p-smad3、smad3和p-smad3/smad3蛋白的表達(dá),并具有劑量反應(yīng)關(guān)系。3通過(guò)sismad2或sismad3轉(zhuǎn)染抵消了利拉魯肽對(duì)mc3t3-e1細(xì)胞向成骨細(xì)胞分化的促進(jìn)作用。4wnt/β-catenin信號(hào)通路阻斷劑dkk-1和pi3k-akt信號(hào)通路阻斷劑ly294002可以抑制利拉魯肽誘導(dǎo)的smad2和smad3相關(guān)蛋白的表達(dá)增加。第三部分exendin-4促進(jìn)前成骨細(xì)胞向成骨分化目的:明確不同濃度exendin-4對(duì)小鼠前成骨細(xì)胞mc3t3-e1向成骨分化的影響。方法:1將普通培養(yǎng)液中培養(yǎng)的mc3t3-e1細(xì)胞設(shè)置為空白對(duì)照組,成骨培養(yǎng)液中培養(yǎng)的mc3t3-e1細(xì)胞設(shè)置為成骨對(duì)照組,成骨干預(yù)組中exendin-4濃度分別設(shè)為10-9mol/l、10-8mol/l和10-7mol/l。在誘導(dǎo)后3、7、14和21天,利用real-timert-pcr和westernblot分析檢測(cè)細(xì)胞glp-1r的mrna和蛋白表達(dá)水平。2檢測(cè)alp活性和茜素紅染色及半定量法評(píng)價(jià)細(xì)胞的分化程度,利用real-timert-pcr和westernblot分析檢測(cè)細(xì)胞runx2和ocn的mrna和蛋白表達(dá)水平。結(jié)果:1exendin-4可使mc3t3-e1細(xì)胞glp-1r的mrna和蛋白表達(dá)水平表達(dá)升高,且呈劑量依賴(lài)性。2mc3t3-e1細(xì)胞alp活性和茜素紅染色半定量的od值隨exendin-4濃度升高而增加。3exendin-4可使mc3t3-e1細(xì)胞runx2和ocn的mrna和蛋白表達(dá)水平表達(dá)升高,且呈劑量依賴(lài)性。第四部分exendin-4對(duì)前成骨細(xì)胞向成骨分化影響的信號(hào)通路研究目的:明確hedgehog/gli1信號(hào)通路是否參與調(diào)控了exendin-4促進(jìn)mc3t3-e1細(xì)胞向成骨分化過(guò)程。方法:1利用小干擾rna(smallinterferingrna,sirna)轉(zhuǎn)染技術(shù)以沉默gli1的基因表達(dá)。取成骨誘導(dǎo)培養(yǎng)條件下的mc3t3-e1細(xì)胞分為6組,空白對(duì)照組、空載體組、gli1-sirna組、空載體+exendin-4組、gli1-sirna+exendin-4組。利用real-timert-pcr和westernblot分析方法檢測(cè)空白對(duì)照組、空載體組和gli1-sirna組中g(shù)li1的表達(dá)水平以確認(rèn)轉(zhuǎn)染效率,并在第7天檢測(cè)所有組的alp活性和runx2組的表達(dá)水平,在第21天進(jìn)行茜素紅染色半定量分析。2應(yīng)用hedgehog信號(hào)通路抑制劑環(huán)杷明(cyclopamine)以檢測(cè)gli1的干擾效率以及阻斷效率,并確定hedgehog/gli1信號(hào)通路在exendin-4對(duì)MC3T3-E1細(xì)胞促成骨分化影響中的作用。結(jié)果:1 Exendin-4可使MC3T3-E1細(xì)胞Hedgehog和Gli1的mRNA和蛋白表達(dá)水平表達(dá)升高,且呈劑量依賴(lài)性。2 SiGli1轉(zhuǎn)染降低了細(xì)胞中Gli1的mRNA和蛋白表達(dá)水平,并抵消了Exendin-4對(duì)MC3T3-E1細(xì)胞向成骨細(xì)胞分化的促進(jìn)作用。3 Hedgehog信號(hào)通路抑制劑環(huán)杷明抵消了Exendin-4對(duì)MC3T3-E1細(xì)胞向成骨細(xì)胞分化的促進(jìn)作用。結(jié)論:1利拉魯肽對(duì)MC3T3-E1細(xì)胞增殖無(wú)顯著影響。2 MC3T3-E1細(xì)胞細(xì)胞質(zhì)與細(xì)胞核中存在GLP-1R,利拉魯肽可以增加成骨培養(yǎng)基中MC3T3-E1細(xì)胞GLP-1R的表達(dá),并具有劑量依賴(lài)性。3利拉魯肽通過(guò)Wnt/β-catenin和PI3K-AKT信號(hào)通路上調(diào)Smad2和Smad3相關(guān)蛋白的表達(dá),呈劑量依賴(lài)性促進(jìn)MC3T3-E1細(xì)胞向成骨分化。4 Exendin-4可以增加成骨培養(yǎng)基中MC3T3-E1細(xì)胞GLP-1R的表達(dá),并通過(guò)Hedgehog/Gli1信號(hào)通路劑量依賴(lài)性促進(jìn)其向成骨分化。
[Abstract]:Glucagon like peptide -1 (glucagon-like peptide 1, GLP-1) is a kind of intestinal secretion of intestinal tract L cell insulin, the main physiological role include eating after a Glucose dependent stimulation of insulin secretion and release, promote pancreatic beta cell proliferation and apoptosis, inhibition of glucagon secretion. Inhibition of gastric emptying, promote satiety produced. But GLP-1 in vivo to two dipeptidyl peptidase IV (dipeptidyl IV peptidase-, DPP- IV) degradation, poor stability, not in clinical application, so researchers developed a variety of GLP-1 analogues. Liraglutide and 97% identity with GLP-1, the half-life of about 12~14 hours; homologous amino acid sequences of 53% Exendin-4 and mammalian GLP-1, polypeptide containing 39 amino acids, 2 hours after injection can reach the peak plasma concentration. Because liraglutide and Exendin-4 will be DPP- IV degradation in vivo, because This not only overcomes the disadvantages of natural GLP-1 susceptible to degradation, and retain a variety of physiological effects and treatment GLP-1 advantage. Liraglutide and Exendin-4 are commonly used in clinical drug, can not only control blood sugar, but also through a variety of ways to influence on bone metabolism in.Zhan found that GLP-1 can inhibit Runt related transcription factor 2 (runt-related transcription FACTOR2, Runx2) produced thereby inhibiting vascular smooth muscle cells of mouse osteoblast differentiation in vitro. However, most studies have confirmed that GLP-1 can promote the osteogenic differentiation. Therefore, GLP-1 and its analogues to promote or inhibit the osteogenic differentiation of undetermined.Smads transforming growth factor beta (transforming growth factor- beta, beta TGF-) signal transduction and regulatory molecules. It has been confirmed that Wnt/ beta -catenin and phosphatidylinositol 3- kinase (phosphatidylinositol 3-kinase PI3K) signal transduction pathway Adjustable Smad2 and Smad3 activation and nuclear transfer, and participate in the osteogenic differentiation process. In addition, Hedgehog is also an important pathway of cell differentiation, Hedgehog signal can make the choice of bone marrow mesenchymal stem cells to differentiate into osteoblasts. For this glucagon like peptide analogues of -1 can promote the osteogenic differentiation and the mechanism of osteoblast cells, this study includes four parts: the first part liraglutide promote pre osteoblast osteogenic differentiation; the second part of liraglutide on bone cells to the signal transduction pathway in osteogenic differentiation of the third part of the Exendin-4; promote the osteoblast osteogenic differentiation; the fourth part Exendin-4 of the to study the signaling pathway of bone cells osteogenic differentiation effect. The first part of liraglutide promote pre osteoblast osteogenic differentiation Objective: to determine the different concentrations of liraglutide on mouse MC3T3-E1 cells proliferation and differentiation of bone The effect. Methods: 1 in vitro mouse bone cells MC3T3-E1 divided into control group and intervention group (10-9mol/l 10-8mol/l, liraglutide, liraglutide 10-7mol/l, liraglutide), inoculated cells after 24,48 and 72h on cell ckk-8 detection and.2 detection of cell cycle by flow cytometry to normal culture in the culture medium of MC3T3-E1 cells is set to the blank control group, osteoblasts cultured in MC3T3-E1 cells arranged into bone control group, a group of backbone pre liraglutide concentrations were set to 10-9mol/l, 10-8mol/l and 10-7mol/l. of different concentrations of liraglutide 48h cells by immunofluorescence localization of cell GLP-1 receptor (glucagon-likepeptide1receptor, GLP-1R the expression site; respectively) on days 3,7,14 and 21 cells were alkaline phosphatase (alkalinephosphatase, ALP) activity assay and alizarin red staining and semi quantitative measurement ; using Westernblot analysis and real-timert-pcr detection of GLP-1R cells, Runx2 and Osteocalcin (osteocalcin, OCN) expression levels of mRNA and protein. Results: there were no significant effects of GLP-1R are cytoplasmic and nuclear.2mc3t3-e1 cells in 1 liraglutide cell viability and cell cycle of MC3T3-E1 cells, liraglutide can increase osteoblast culture the expression of MC3T3-E1 GLP-1R cells in the medium in a dose-dependent manner; in osteoblast culture medium added 10-7mol/l liraglutide after 14 days the expression of GLP-1R increased obviously.3 liraglutide dose dependently stimulated MC3T3-E1 cells to express mRNA protein level and osteogenic differentiation of the ALP activity and calcium deposition with.4 peptide upregulation of Runx2 and OCN, in a dose-dependent manner; the expression level of mRNA protein and Runx2 reached the peak on the 7 day, the expression level of mRNA protein and OCN was reached in 21 days Peak. The second part of liraglutide on pre osteoblasts to signal pathway of osteogenic differentiation effect: To explore Smad2 and Smad3 are involved in the promotion of liraglutide mouse like bone cell MC3T3-E1 to osteogenic differentiation, and further clarify the transcription and protein expression of liraglutide through wnt/ beta -catenin signal pathway and PI3K-Akt signal Smad2 pathway and Smad3. Methods: 1 normal cultured MC3T3-E1 cells were set to blank control group, osteoblasts cultured in MC3T3-E1 cells arranged into bone control group, a group of backbone pre liraglutide concentrations were set to 10-9mol/l, 10-8mol/l and 10-7mol/l. using real-timert-pcr to detect Smad2 and Smad3 the level of gene expression analysis techniques to detect p-Smad2, Smad2 with Westernblot, the expression of p-smad3 and Smad3 protein in cultured mouse bone cells into the level of MC.2 in vitro 3T3-E1, by small interfering RNA (smallinterferingrna, siRNA) expression to silence Smad2 gene and Smad3 Gene. The osteogenic induction in cultured MC3T3-E1 cells were divided into 8 groups under the conditions, namely control group, vector group, plasmid + liraglutide group, smad2-sirna group, sismad2+ group, smad3-sirna group and liraglutide. Sismad3+ liraglutide group detected by real-timert-pcr cells. Smad2, Smad3 and Runx2 gene expression level analysis to detect p-Smad2, Smad2, p-smad3 by Westernblot, the expression level of Smad3 and Runx2 protein were tested by ALP activity and alizarin red staining and semi quantitative evaluation method of cell differentiation.2 we further applied the wnt/ beta -catenin signal pathway inhibitor DKK-1 and PI3K-Akt signaling pathway inhibitor LY294002 to determine the effects of wnt/ beta -catenin and PI3K-Akt signal pathways of Smad2 and Smad3 in liraglutide in Results: 1. The role of liraglutide upregulation of Smad2 and Smad3 mRNA level, and there was a dose-response relationship between.2 liraglutide can increase p-Smad2, Smad2, p-smad2/smad2, p-smad3, Smad3 and p-smad3/smad3 protein expression, and there was a dose-response relationship between.3 with sismad2 or sismad3 was offset by liraglutide on MC3T3-E1 cells to differentiate into osteoblasts the increased expression of.4wnt/ beta -catenin signaling pathway related protein Smad3 and Smad2 blocking agent DKK-1 and PI3K-Akt signal pathway inhibitor LY294002 can inhibit liraglutide induced by exendin-4. In the third part, promote the osteoblast osteogenic differentiation Objective: to determine the different concentrations of exendin-4 on mouse osteoblastic MC3T3-E1 cells to osteogenic differentiation in vitro methods: 1 normal cultured MC3T3-E1 cells were set to blank control group, osteoblasts cultured in MC3T3-E1 cell set Osteogenic control group, into the backbone of the concentration of exendin-4 in the pre group were divided into 10-9mol/l, 10-8mol/l and 10-7mol/l. in 3,7,14 and 21 days after induction, analysis by real-timert-pcr and Westernblot mRNA and protein were detected the expression of GLP-1R differentiation level.2 ALP activity detection and evaluation of alizarin red staining and semi quantitative method using analysis of real-timert-pcr cells. The expression of Westernblot and mRNA and protein levels of OCN and Runx2 were detected. Results: 1exendin-4 mRNA and protein expression level of GLP-1R expression in MC3T3-E1 cells increased in a dose-dependent manner in.2mc3t3-e1 cells ALP activity and alizarin red staining and semi quantitative OD value can be increased.3exendin-4 mRNA and protein in MC3T3-E1 cells and the expression of OCN Runx2 the expression level increased with the concentration of exendin-4 increased in a dose-dependent manner. The fourth part exendin-4 of pre osteoblast osteogenic differentiation effect Objective to study the signal pathway: clear hedgehog/gli1 signaling pathway is involved in the regulation of exendin-4 promotes MC3T3-E1 cell osteogenic differentiation process. Methods: 1 using small interfering RNA (smallinterferingrna, siRNA) transfection technique to silence Gli1 gene expression. The osteogenic induction culture conditions of MC3T3-E1 cells were divided into 6 groups, control group, empty group, gli1-sirna group, empty vector group +exendin-4, gli1-sirna+exendin-4 group. Using real-timert-pcr and Westernblot analysis method to detect the expression of Gli1 water control group, empty vector group and gli1-sirna group in the flat to confirm the transfection efficiency and expression level of ALP activity and Runx2 group of all groups were detected in seventh days, semi quantitative alizarin red.2 staining analysis application of hedgehog signaling pathway inhibitor cyclopamine in twenty-first days (cyclopamine) to interfere with the efficiency of Gli1 detection and blocking efficiency, and to determine the hedgehog/ The Gli1 signaling pathway in the differentiation of osteogenic effect on MC3T3-E1 cells in exendin-4. Results: 1 Exendin-4 can make the mRNA and Hedgehog proteins in MC3T3-E1 cells and the expression level of Gli1 expression increased in a dose-dependent manner in.2 cells transfected with SiGli1 reduced Gli1 mRNA and protein expression level, and the offset of Exendin-4 on MC3T3-E1 cells osteogenic differentiation promoting effect of.3 Hedgehog signaling pathway inhibitor cyclopamine offset Exendin-4 of MC3T3-E1 cells to differentiate into osteoblasts to promote the role of 1. Conclusion: liraglutide has no significant effect on GLP-1R.2 MC3T3-E1 cell cytoplasm and nucleus of MC3T3-E1 cells proliferation, liraglutide can increase osteoblast cultured MC3T3-E1 cells express GLP-1R in the medium, and had dose dependent.3 liraglutide by Wnt/ beta -catenin and PI3K-AKT signaling pathway in the up regulation of Smad2 and Smad3 related protein table Da promoted the osteogenic differentiation of MC3T3-E1 cells in a dose-dependent manner..4 Exendin-4 increased the expression of GLP-1R in MC3T3-E1 cells and promoted the osteogenic differentiation through Hedgehog/Gli1 signaling pathway in a dose-dependent manner.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R587.1

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 王運(yùn)濤;骨髓間充質(zhì)干細(xì)胞成骨分化調(diào)控的研究進(jìn)展[J];國(guó)外醫(yī)學(xué)(生物醫(yī)學(xué)工程分冊(cè));2003年01期

2 井燕;李良;李毅;陳孟詩(shī);吳文超;陳槐卿;劉小菁;;力學(xué)應(yīng)變對(duì)大鼠骨髓間充質(zhì)干細(xì)胞增殖和成骨分化能力的影響[J];生物醫(yī)學(xué)工程學(xué)雜志;2006年03期

3 崔向榮;蘇偉;黃釗;覃萬(wàn)安;;電磁場(chǎng)促進(jìn)骨髓間充質(zhì)干細(xì)胞成骨分化的研究進(jìn)展[J];中國(guó)醫(yī)學(xué)物理學(xué)雜志;2011年04期

4 彭飛;鄭亞?wèn)|;徐西強(qiáng);虞冀哲;吳華;;620nm低能量紅光對(duì)骨髓間充質(zhì)干細(xì)胞成骨分化的影響[J];激光生物學(xué)報(bào);2011年03期

5 趙領(lǐng)洲;劉麗;吳織芬;;微米坑/納米管氧化鈦形貌對(duì)骨髓間充質(zhì)干細(xì)胞成骨分化的作用[J];醫(yī)學(xué)爭(zhēng)鳴;2012年04期

6 楊姣;夏雷;湯郁;陸化;費(fèi)小明;;腫瘤壞死因子預(yù)處理促進(jìn)骨髓間充質(zhì)干細(xì)胞成骨分化潛能[J];南京醫(yī)科大學(xué)學(xué)報(bào)(自然科學(xué)版);2014年03期

7 王晶;張洹;;-80℃一步法凍存對(duì)成人骨髓間充質(zhì)干細(xì)胞成骨分化能力的影響[J];廣東醫(yī)學(xué);2007年03期

8 陳翠平;羅新;;17β-雌二醇對(duì)大鼠骨髓間充質(zhì)干細(xì)胞成骨分化的作用[J];中國(guó)骨質(zhì)疏松雜志;2007年05期

9 ;骨髓間充質(zhì)干細(xì)胞的成骨分化[J];中國(guó)組織工程研究與臨床康復(fù);2010年10期

10 吳玉瓊;房兵;江凌勇;;間歇牽拉應(yīng)變對(duì)大鼠骨髓間充質(zhì)干細(xì)胞增殖與成骨分化的影響[J];醫(yī)用生物力學(xué);2011年06期

相關(guān)會(huì)議論文 前10條

1 鄭亮;鄭雅元;崔燎;劉鈺瑜;;四羥基二苯乙烯-2-O-β-D-葡萄糖苷對(duì)大鼠骨髓間充質(zhì)干細(xì)胞成骨分化的作用及機(jī)制研究[A];中華醫(yī)學(xué)會(huì)第七次全國(guó)骨質(zhì)疏松和骨礦鹽疾病學(xué)術(shù)會(huì)議論文匯編[C];2013年

2 吳江;陳槐卿;K-LP.SUNG;;鈦顆粒負(fù)荷影響骨髓間充質(zhì)干細(xì)胞成骨分化能力的機(jī)理[A];全國(guó)首屆青年復(fù)合材料學(xué)術(shù)交流會(huì)論文集[C];2007年

3 吳江;陳槐卿;李良;尹光福;K-L P．SUNG;;鈦顆粒負(fù)荷影響骨髓間充質(zhì)干細(xì)胞成骨分化能力的機(jī)理[A];中國(guó)復(fù)合材料學(xué)術(shù)研討會(huì)論文集[C];2005年

4 陳海嘯;洪盾;萬(wàn)曉晨;李繼承;;腸毒素C聯(lián)合維生素C對(duì)骨髓間充質(zhì)干細(xì)胞成骨分化的影響研究[A];2008年浙江省骨科學(xué)學(xué)術(shù)年會(huì)論文匯編[C];2008年

5 袁風(fēng)紅;鄒耀紅;高愷言;俞可佳;;地塞米松對(duì)體外人骨髓基質(zhì)細(xì)胞增殖及成骨分化的影響[A];全國(guó)自身免疫性疾病專(zhuān)題研討會(huì)暨第十一次全國(guó)風(fēng)濕病學(xué)學(xué)術(shù)年會(huì)論文匯編[C];2006年

6 宋忠臣;束蓉;董家辰;李松;;低氧對(duì)牙周膜成纖維細(xì)胞增殖和成骨分化的影響[A];第十次全國(guó)牙周病學(xué)學(xué)術(shù)會(huì)議論文摘要匯編[C];2014年

7 董家辰;束蓉;宋忠臣;;炎癥微環(huán)境對(duì)人牙周膜成纖維細(xì)胞增殖與成骨分化的影響[A];第十次全國(guó)牙周病學(xué)學(xué)術(shù)會(huì)議論文摘要匯編[C];2014年

8 孫楠;楊力;張振;張樺;陳宏;蔡德鴻;;晚期氧化蛋白產(chǎn)物對(duì)大鼠骨髓間充質(zhì)干細(xì)胞增殖及向成骨分化的影響[A];中華醫(yī)學(xué)會(huì)第十二次全國(guó)內(nèi)分泌學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2013年

9 馬雪;孟靜茹;賈敏;王寧;胡靜;周穎;羅曉星;;胰高血糖素樣肽-1類(lèi)似物對(duì)大鼠骨髓間充質(zhì)干細(xì)胞增殖與成骨分化的影響[A];第十一屆全國(guó)青年藥學(xué)工作者最新科研成果交流會(huì)論文集[C];2012年

10 林和敏;;成骨分化的人臍血間充質(zhì)干細(xì)胞免疫原性研究[A];2013年全國(guó)激光醫(yī)學(xué)學(xué)術(shù)聯(lián)合會(huì)議暨2013年浙江省醫(yī)學(xué)會(huì)整形美容學(xué)術(shù)年會(huì)論文匯編[C];2013年

相關(guān)博士學(xué)位論文 前10條

1 龔逸明;microRNAs調(diào)控Satb2介導(dǎo)的骨髓基質(zhì)干細(xì)胞成骨分化的作用研究[D];復(fù)旦大學(xué);2014年

2 李松濤;EphB信號(hào)在軸向仿生壓應(yīng)力調(diào)控MSC成骨分化中的作用和機(jī)制研究[D];第三軍醫(yī)大學(xué);2015年

3 方文;純鈦表面WNT信號(hào)通路調(diào)控BMSCs成骨分化的機(jī)制研究[D];浙江大學(xué);2014年

4 劉世宇;移植外源性MSCs持久恢復(fù)宿主MSCs功能的機(jī)制研究[D];第四軍醫(yī)大學(xué);2015年

5 張莉;Fgfr2~(S252W/+)小鼠骨量、骨結(jié)構(gòu)特性及BMSCs成骨分化調(diào)控機(jī)制的研究[D];第三軍醫(yī)大學(xué);2015年

6 劉旭杰;材料性質(zhì)調(diào)控干細(xì)胞成骨分化及殼聚糖基骨修復(fù)材料[D];清華大學(xué);2015年

7 文采;多孔礦化水凝膠材料誘導(dǎo)人胚胎干細(xì)胞成骨分化的研究[D];東南大學(xué);2015年

8 吳毛;胸腰段椎體骨折形態(tài)與椎管狹窄相關(guān)性研究及Sclerostin對(duì)成骨分化的影響[D];蘇州大學(xué);2016年

9 黃江;激活HIF-1α對(duì)骨折愈合的影響及誘導(dǎo)miR-429對(duì)MC3T3-E1細(xì)胞成骨分化的作用機(jī)制[D];首都醫(yī)科大學(xué);2016年

10 侯秋科;龜板有效成分促間充質(zhì)干細(xì)胞成骨分化的miRNA-VDR網(wǎng)絡(luò)機(jī)制[D];廣州中醫(yī)藥大學(xué);2016年

相關(guān)碩士學(xué)位論文 前10條

1 吳小瑩;腦源性神經(jīng)營(yíng)養(yǎng)因子對(duì)人脂肪干細(xì)胞增殖與成骨分化的作用[D];北京協(xié)和醫(yī)學(xué)院;2015年

2 秦子順;淫羊藿苷對(duì)人牙周膜干細(xì)胞的增殖和成骨分化的影響[D];蘭州大學(xué);2015年

3 劉可;miR-106bE靶向調(diào)控BMP2參與間充質(zhì)干細(xì)胞成骨分化與體內(nèi)骨形成[D];蘇州大學(xué);2015年

4 付雪杰;MSCs與去分化MSCs在成骨分化過(guò)程中免疫原性上調(diào)的研究[D];蘇州大學(xué);2015年

5 崔陽(yáng)陽(yáng);蛋白激酶C在小鼠骨髓間充質(zhì)干細(xì)胞成骨分化中的作用研究[D];新鄉(xiāng)醫(yī)學(xué)院;2015年

6 嚴(yán)一杰;體外誘導(dǎo)人腎間質(zhì)成纖維細(xì)胞成骨分化的實(shí)驗(yàn)研究[D];廣西醫(yī)科大學(xué);2015年

7 高羽萱;直流微電場(chǎng)對(duì)種植體周骨髓間充質(zhì)干細(xì)胞遷移和成骨影響的研究[D];中國(guó)人民解放軍醫(yī)學(xué)院;2015年

8 郭中豪;甲狀旁腺激素對(duì)大鼠骨髓間充質(zhì)干細(xì)胞成骨分化的影響[D];山西醫(yī)科大學(xué);2015年

9 李慧垠;高脂環(huán)境下大鼠BMSCs成骨分化過(guò)程中Wnt通路相關(guān)因子的表達(dá)變化[D];山東大學(xué);2015年

10 聶曉萌;MicroRNA靶向Id1對(duì)BMSCs成骨分化的影響[D];山東大學(xué);2015年

，

本文編號(hào)：1686936