人工关节假体阴极弧沉积氧化锆膜对成骨细胞生物活性影响的实验研究

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英文题名：Activity of Osteoblast-like Cells on ZrO_2Film Prepared by Catholic Arc Deposition 作者：章筛林 论文级别：博士 学科专业名称：骨外科学 中文关键词：真空阴极弧沉积 ; 氧化锆 ; 成骨细胞 ; 粘附 ; 增殖 ; 真空阴极弧沉积 ; 氧化锆 ; 表征 ; 真空阴极弧沉积 ; 氧化锆 ; 成骨细胞 ; 分化 ; 真空阴极弧沉积 ; 氧化锆 ; 成骨细胞 ; OPG ; RANKL ; 真空阴极弧沉积 ; 氧化锆 ; 成骨细胞 ; 信号传导 ; 促分裂素原活化蛋白激酶 英文关键词：cathodic arc deposition ; ZrO_2 ; surface characterizationscathodic arc deposition ; ZrO_2 ; osteoblast ; adhesion ; proliferationcathodic arc deposition ; ZrO_2 ; osteoblast ; differentiationcathodic arc deposition ; ZrO_2 ; osteoblast ; OPG ; RANKLcathodic arc deposition ; ZrO_2 ; osteoblast ; signal pathway ; MAPK 学位年度：2013 导师：孙俊英 学科代码：100210 学位授予单位：苏州大学 论文提交日期：2013-03-01

摘要

[摘要]目的：试图采用磁过滤真空阴极弧沉积法在钛金属假体表面制备氧化锆膜，并检测其表征。方法：采用磁过滤真空阴极弧沉积法在纯钛片表面制备氧化锆膜，然后对氧化锆膜的形貌特征、化学组成、相组成等进行表征检测。结果：检测显示真空阴极弧沉积制备的氧化锆膜比较均匀、光滑、致密，具有纳米结构的表面。结论：采用磁过滤真空阴极弧沉积系统可在纯钛表面制备均匀、致密的氧化锆膜，制备的氧化锆膜具有纳米结构的表面，阴极弧沉积氧化锆膜的纳米表面结构可能与它的生物活性有关。
     [摘要]目的：探讨阴极弧沉积氧化锆膜对成骨样MG63细胞粘附及增殖活性的影响。方法：以阴极弧沉积ZrO_2膜作为实验组，纯Ti作为对照组，分别按一定的密度接种MG63细胞进行培养。MTT法检测1、6、12、24小时两组材料表面附着的成骨细胞数；扫描电镜观察12和24小时成骨细胞在两组材料表面的铺展情况；鬼笔环肽荧光染色倒置荧光显微镜观察12和24小时两组材料表面细胞骨架蛋白的表达。CCK-8法检测1、4、7、10天时两组材料表面成骨细胞的增殖活性。结果：MTT结果显示：1小时后，两组样品表面MG63细胞附着的数量差异无统计学意义（P＞0.05）；6、12和24小时后，ZrO_2膜表面的细胞数显著多于纯Ti表面，且差异具有统计学意义（P＜0.05）。扫描电镜观察结果显示12和24小时后ZrO_2组的细胞铺展优于Ti组，荧光显微镜观察结果显示12和24小时后ZrO_2组表面细胞骨架蛋白的表达多于Ti组；CCK结果显示：培养4天及7天后，ZrO_2膜表面的细胞增殖活性显著高于纯Ti表面，且差异具有统计学意义（P＜0.05）。结论：人工关节假体表面阴极弧沉积制备的氧化锆膜具有促进成骨细胞粘附及增殖的能力。
     [摘要]目的：探讨阴极弧沉积氧化锆膜对成骨样MG63细胞分化表型标志物的影响。方法：以阴极弧沉积ZrO_2膜作为实验组，纯Ti作为对照组，分别按一定的密度接种MG63细胞进行培养。分别于第1、4、7、10天收集标本，检测碱性磷酸酶（ALP）活性；以定量RT-PCR法检测成骨细胞分化标志物碱性磷酸酶、I型胶原（COLI）及骨钙素（OC）的基因表达情况；荧光染色倒置荧光显微镜观察4天时COLI蛋白的表达；ELISA检测1、4、7、10天时成骨细胞分泌OC蛋白量。结果：在培养第1天时，两组碱性磷酸酶活性及基因表达差异无统计学意义（p＞0.05）；随着培养时间的延长，两组碱性磷酸酶活性及基因表达均呈现出逐渐增加的趋势，第4、7、10天时，ZrO_2组碱性磷酸酶活性及基因表达显著高于纯Ti组（p＜0.05）。第1天时，且两组COLI基因表达差异无统计学意义（p＞0.05）；在第4天及7天时，ZrO_2组COLI基因表达显著高于纯Ti组（p＜0.05），在第10天时，两组COLI基因表达无统计学差异（p＞0.05）。在第1天和第4天培养时，两组OC基因表达无统计学差异（p＞0.05）；但在第7天和第10天时，ZrO_2组的OC基因表达显著高于纯Ti组（p＜0.05）。第4天时，ZrO_2组表面的COLI蛋白合成量多于Ti组。两组OC蛋白分泌量在第1、4天时无统计学差异（p＞0.05）；但在第7、10天时，ZrO_2组OC蛋白分泌量均显著高于Ti组（p＜0.05）。结论：阴极弧沉积氧化锆膜具有提高MG63细胞分化表型标志物水平的能力，表明阴极弧沉积氧化锆膜是一种具有良好生物活性的涂层材料。
     [摘要]目的：探讨人工关节假体表面阴极弧沉积氧化锆膜对成骨细胞破骨细胞分化相关基因表达及蛋白分泌的影响。方法：以阴极弧沉积ZrO_2膜作为实验组，纯Ti作为对照组，分别按一定的密度接种MG63细胞进行培养。分别于第1、4、7、10天收集标本，以定量RT-PCR法检测成骨细胞破骨细胞分化相关的骨保护素（OPG）和核因子κ B受体活化因子配体（RANKL）基因表达情况；ELISA检测1、4、7、10天时成骨细胞分泌OPG和RANKL蛋白量。结果：第1天及第4天时，两组OPG基因表达无统计学差异（p＞0.05）；第7天及第10天时，ZrO_2组OPG基因表达显著高于Ti组（p＜0.05）。第1天及第4天时，两组RANKL基因表达无显著差异（p＞0.05）；在第7天及第10天时，ZrO_2组的基因表达显著低于Ti组（p＜0.05）。培养第1天及第4天时，两组样品表面的成骨细胞OPG蛋白分泌无统计学差异（p＞0.05）；第7天及第10天时，ZrO_2组OPG蛋白分泌显著高于Ti组（p＜0.05）。第1天及第4天时，两组样品表面的成骨细胞RANKL蛋白分泌无显著差异（p＞0.05）；第7天及第10天时，ZrO_2组的RANKL蛋白分泌显著低于Ti组（p＜0.05）。结论：人工关节假体表面阴极弧沉积氧化锆膜能够上调成骨细胞OPG水平，同时下调RANKL水平，提高OPG/RANKL相对比率，从而抑制破骨细胞的分化和活性。
     ［摘要］目的：探讨人工关节假体表面阴极弧沉积氧化锆膜对成骨样MG63细胞活性影响的可能信号传导通路。方法：以阴极弧沉积ZrO_2膜作为实验组，纯Ti作为对照组，分别按照一定的密度在表面接种MG63细胞进行培养。分别于第6小时，24小时，4天，7天后四个时间点收集标本，检测整合素β1、FAK、ERK1、ERK2、c-fos及c-jun的基因表达。结果：6、24小时及4天后，ZrO_2组整合素β1基因表达显著高于Ti组（p＜0.05）；7天后，两组整合素β1表达无统计学差异（p＞0.05）。6、24小时及4天后，ZrO_2组FAK基因表达显著高于Ti组（p＜0.05）；7天后，两组FAK基因表达无统计学差异（p＞0.05）；6小时及24小时后，ZrO_2组ERK1基因表达显著高于Ti组（p＜0.05）；4天及7天后，两组ERK1基因表达无显著差异（p＞0.05）。6、24小时及4天后，ZrO_2组ERK2基因表达显著高于T组（p＜0.05）；7天后，两组样品表面的ERK2基因表达无显著差异（p＞0.05）。6、24小时、4天及7天后，ZrO_2组c-fos基因表达显著高于Ti组（p＜0.05）。6、24小时及4天后，ZrO_2组c-jun表达显著高于Ti组（p＜0.05）；7天后，两组样品表面的c-jun基因表达无统计学差异（p＞0.05）。结论：人工关节假体表面阴极弧沉积氧化锆膜可能通过整合素介导的MAPK/ERK信号传导途径影响细胞活性。
[Abstract] Objective: To prepare ZrO_2film by cathodic arc deposition (CAD)，and to detect thecharacterizations of the ZrO_2film. Method: ZrO_2film was prepared on titanium by cathodic arcdeposition. The surface topography was characterized by scanning electron microscopy (SEM) andatomic force microscopy (AFM). The element composition of the films was detected by X-rayphotoelectron spectroscopy (XPS). The phase of films was identified by thin film X-ray diffraction(XRD). Result: SEM view images show that the ZrO_2film was uniform, dense and smooth. AFM resultindicates that the ZrO_2film deposited by filtered cathodic arc deposition has a nanostructured surface.XRD analysis indicates the ZrO_2film were amorphous. XPS spectra of ZrO_2film shows C1s, O1s, Ti3p,Zr3d, Zr3p, Zr3s, and Zr4s peaks are observed. Conclusion: Amorphous ZrO_2film can be deposited onTi disks by cathodic arc deposition. The deposited ZrO_2film seems to be uniform, dense and smoothand has a nanostructured surface, which may contribute to its bioactivity.
     [Abstract] Objective: To evaluate the effect of ZrO_2film fabricated by cathodic arc deposition onadhesion and proliferation of osteoblast-like MG63cells. Method: Osteoblast-like MG63cells werecultured on ZrO_2film and Ti respectively. MTT was used to measure the number of cell attachmentafter1,6,12,24h of cultivation. Cell spreading was investigated by scanning electron microscopy(SEM). The expression of actin on each sample was observed by immunofluorescence. Cellproliferation was assessed using a Cell Counting Kit-8(CCK-8) after1,4,7,10days of cultivation.Result: The MTT result showed that after6,12,24h of culture, the number of cell attachment on ZrO_2films was more than that on Ti (p <0.05). The SEM study showed that MG63cells spread better onZrO_2films than on Ti. The fluorescence micrographs of actin stress fibers demonstrated thatwell-defined actin stress fibers distributed through the body of cells cultured on ZrO_2films afterincubated for12and24h. The CCK-8assay indicated that the ZrO_2films promoted the proliferation ofMG63cells. Conclusion: It was proved that the ZrO_2film fabricated by cathodic arc deposition was able to promote adhesion and proliferation of osteoblast-like MG63cells, suggesting that the ZrO_2filmis worth further consideration for orthopedic implant applications.
     [Abstract] Objective: To evaluate the effect of ZrO_2film fabricated by cathodic arc deposition ondifferentiation of osteoblast-like MG63cells. Method: Osteoblast-like MG63cells were cultured onZrO_2film and Ti respectively. After1,4,7,10days of incubation respectively, samples were collectedfor assay. ALP activity and gene expression of alkaline phosphates (ALP), Type I collagen (COLI),osteocalcin (OC) were assessed. The production of COLI at day4was evaluated byimmunofluorescence and the OC protein secretion after1,4,7,10days of culture were investigated byELISA assay. Result: The ALP activity increased steadily on both surfaces over the course ofincubation. By days4,7and10, the ALP activity of cells on ZrO_2films was significantly higher than onTi (p <0.05). The ALP mRNA expression of cells on ZrO_2films was significantly higher than on Tiafter cultured for4,7and10days (p <0.05). The COLI mRNA expression of cells on ZrO_2films wassignificantly higher than on Ti after cultured for4and7days (p <0.05). The OC mRNA expression onZrO_2films was significantly higher than on Ti after7and10days of incubation (p <0.05). Theproduction of type COLI by immunofluorescence showed that cells on ZrO_2films produced more COLIthan on Ti after4days of culture. The OC protein secretion on ZrO_2films was higher than on Ti after7,10days of culture. Conclusion: ZrO_2film was able to enhance induction of osteoblastic phenotype ofosteoblast-like MG63cells, which indicated that ZrO_2film may be a favorable bioactive biomaterial.
     [Abstract] Objective: To evaluate the effect of ZrO_2film fabricated by cathodic arc deposition onosteoclastogenic gene expression and their protein synthesis of osteoblast-like MG63cells. Method:Osteoblast-like MG63cells were cultured on ZrO_2film and Ti respectively. After1,4,7,10days ofincubation respectively, samples were collected for assay. The osteoclastogenic gene expression (OPG,RANKL) and their protein secretion were analyzed by real time PCR and ELISA respectively. Result:The OPG mRNA level on both surfaces appeared equal at day1and4(p>0.05). After7and10days ofculture, the OPG mRNA level on ZrO_2films displayed higher than that on Ti (p <0.05). The RANKLmRNA expression level on both surfaces showed no significant difference at day1and4(p>0.05). However, the RANKL mRNA expression level of cells on ZrO2films appeared lower than on Ti at day7and10(p <0.05). The OPG protein secretion on both surfaces appeared equal at day1and4(p>0.05). The OPG protein secretion on ZrO2films was significantly higher than on Ti at day7and10(p <0.05). The RANKL protein secretion on both surfaces appeared equal at day1and4(p>0.05). TheRANKL protein secretion on ZrO2films was lower than on Ti at day7and10(p <0.05). Conclusion:ZrO2film fabricated by cathodic arc deposition was able to enhance the expression of OPG geneexpression and protein synthesis while reduce the RANKL gene expression and protein synthesis,leading to increase in the ratio of OPG/RANKL, which may help contribute to the successful
     [Abstract] Objective: To explore the possible signal transduction passway mediating osteoblasticactivity on ZrO_2film fabricated by cathodic arc deposition. Method: Osteoblast-like MG63cells werecultured on ZrO_2film and Ti respectively. After6h,24h,4d,7d of cultivation respectively, sampleswere collected for assay. Gene expression of integrin β1, focal adhesion kinase (FAK), extracellularregulated kinases (ERK, including ERK1and ERK2), c-fos and c-jun were measured by real-time PCR.Result: After6h,24h and4d of culture, integrin β1mRNA expression on ZrO_2films wassignificantly higher than on Ti (p <0.05). The gene expression of FAK on ZrO_2films was significantlyhigher than that on Ti at6h,24h and4d (p <0.05). The gene expression of ERK1on ZrO_2films wassignificantly higher than on Ti at6h and24h (p <0.05). The gene expression of ERK2on ZrO_2filmswas significantly higher than on Ti at6h,24h and4d (p <0.05). The gene expression of c-fos on ZrO_2films appeared significantly higher than on Ti disks (p <0.05) at all time points. After cultured for6h,24h and4d, c-jun gene expression appeared significantly higher on ZrO_2films than on Ti disks (p <0.05). Conclusion: The enhanced cell activity on ZrO_2films may be partially regulated by integrin β1mediated MAPK/ERK pathway.

引文

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