补肾中药有效成分对大鼠骨损伤愈合及血液流变学的影响

背景：补肾中药为骨伤科常用药,但对不同有效成分用于骨愈合的比较研究尚缺乏。 目的：观察不同补肾中药有效成分对骨损伤大鼠骨愈合及血液流变学的影响。 方法：建立大鼠股骨干骨折模型并分别用提取的骨碎补总黄酮、淫羊藿总黄酮、菟丝子总黄酮、柚皮甙、槲皮素,以及橙皮甙对造模大鼠进行灌胃治疗。21 d后取血及骨标本,检测大鼠骨愈合程度和血液流变学指标。 结果与结论：不同补肾中药有效成分均对骨愈合有益,且骨碎补总黄酮、淫羊藿总黄酮效果优于其他4种药物。骨碎补总黄酮和淫羊藿总黄酮可有效抑制低剪切速下大鼠的血液黏度,降低红细胞聚集指数及血小板聚集性和黏附性(P < 0.05),但对红细胞变形性无显著作用。说明补肾中药有效成分可促进骨损伤的愈合,且对血液流变学有一定作用,以骨碎补总黄酮效果最佳。     

EF延缓HPAT轴衰老的基因表达谱研究

目的：淫羊藿总黄酮(EF)延缓下丘脑-垂体-肾上腺-胸腺(HPAT)轴衰老的分子机制。方法：利用基因芯片技术，分别检测淫羊藿总黄酮组、右归饮组、桃红四物汤组、老年大鼠对照组及青年大鼠对照组下丘脑、垂体、肾上腺、脾脏淋巴细胞的基因表达谱。结果：老年大鼠和青年大鼠相比，HPAT轴多种神经递质、激素、细胞因子或其受体表达下调；EF组HPAT轴多种神经递质、激素、细胞因子或其受体表达上调；右归饮组及桃红四物汤组未见广泛的调节作用。结论：老年大鼠HPAT轴与生长、发育、衰老相关的基因表达以衰退的表现为主；EF能上调神经递质受体的表达并通过NEI网络的下行通路激活神经内分泌和免疫系统；通过下调促凋亡、抗增殖基因，上调抗凋亡、促增殖基因的表达，重塑淋巴细胞基因表达的平衡，延缓免疫衰老。     

衰老进程中大鼠淋巴细胞凋亡率的比较研究及淫羊藿总黄酮的干预作用

目的：比较研究衰老进程中各年龄段大鼠淋巴细胞凋亡率的差异及淫羊藿总黄酮（EF）对老年期细胞凋亡的干预作用。方法：选用SD大鼠脾脏分离的淋巴细胞为研究对象,用流式细胞方法,比较从出生后3天直到27月龄衰老进程中,各代表性年龄段的细胞凋亡率差异,并观察EF对老年过度细胞凋亡的影响作用。结果：刚出生3天组的凋亡率最低,随着增龄,细胞凋亡率逐渐升高,仅10月龄组例外,其凋亡率小于4月龄组,27月龄的细胞凋亡率最高。EF干预后,27月龄组的细胞凋亡率明显下降,介于10月龄与18月龄之间水平,以上差异均有显著统计学意义（P〈0.05～P〈0.001）。结论：在衰老进程中,大鼠淋巴细胞的凋亡率随增龄而逐渐升高,在老年大鼠存在过度凋亡现象,而EF可抑制老年淋巴细胞过度凋亡。     

淫羊藿颗粒剂联合三苯氧胺对乳腺癌MCF-7细胞增殖的调节作用

目的探讨补肾中药淫羊藿或与三苯氧胺(TAM)合用是否有促人乳腺癌MCF-7细胞增殖的作用。方法设立空白、E2及TAM对照组,观察淫羊藿颗粒剂单用及联合TAM在不同剂量和作用时间下对MCF-7细胞的生长的影响。应用MTT法观察细胞增殖情况。结果淫羊藿对乳腺癌MCF-7细胞生长的影响因浓度的不同而不同:低浓度的淫羊藿颗粒剂对乳腺癌细胞MCF-7的促增殖作用不明显(P>0.05)。淫羊藿与TAM联合作用于MCF-7细胞,无明显促细胞增殖的作用(P>0.05),而中等剂量的淫羊藿颗粒有弱雌激素样作用(P<0.05),但可被TAM拮抗。结论淫羊藿联合TAM作用于乳腺癌MCF-7细胞,无促癌细胞生长的作用。但单独应用淫羊藿治疗乳腺癌患者,其使用剂量及持续时间尚需进一步探索。     

补肾中药成分配伍对成骨细胞成骨活性及Smad4 mRNA表达的影响

背景：补肾中药对动物及细胞实验研究提示具有防治骨质疏松及改善骨代谢作用,但补肾中药的配伍研究较少且复杂,且有效作用成分之间的相互作用及药物物质基础尚不确定,筛选最佳配伍困难。 目的：通过采用不同补肾中药成分配伍,对新生SD大鼠成骨细胞进行干预性培养,并对其增殖、分化、Smad4 mRNA表达进行测定,从而筛选并确定补肾中药的最佳配伍。 方法：第5代成骨细胞分为5组：淫羊藿苷组细胞中加入1×10^-5 mol/L的淫羊藿苷;淫羊藿苷+柚皮苷组细胞中加入1×10^-5 mol/L淫羊藿苷+1×10^-5 mol/L柚皮苷;淫羊藿苷+薯蓣皂苷元组细胞中加入1×10^-5 mol/L淫羊藿苷+1×10^-5 mol/L薯蓣皂苷元;淫羊藿苷+梓醇组细胞中加入1×10^-5 mol/L淫羊藿苷+1×10^-5 mol/L梓醇;对照组细胞中加入10 μL生理盐水。每组6个复孔。 结果与结论：与对照组相比,淫羊藿苷+柚皮苷组和淫羊藿苷+薯蓣皂苷元组成骨细胞增殖能力及Smad4 mRNA表达水平增加,且培养72 h时,淫羊藿苷+柚皮苷组成骨细胞增殖能力最强。48 h时,淫羊藿苷+柚皮苷组和淫羊藿苷+薯蓣皂苷元组成骨细胞碱性磷酸酶活性高于对照组;72 h,淫羊藿苷+柚皮苷组和淫羊藿苷+梓醇组成骨细胞碱性磷酸酶活性高于对照组。提示淫羊藿苷等补肾中药成分配伍可以影响成骨细胞的成骨活性,且其中以淫羊藿苷配伍柚皮苷的作用最强。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

淫羊藿苷减轻高糖诱导的C2C12肌管细胞胰岛素抵抗

目的:探讨淫羊藿苷对高糖诱导的C2C12肌管细胞胰岛素抵抗的影响及其可能的机制。方法:高糖(25 mmol/L葡萄糖)诱导C2C12肌管细胞胰岛素抵抗,并观察淫羊藿苷在高糖条件下对Akt T308磷酸化、葡萄糖转运蛋白4(GLUT4)膜转位及葡萄糖摄取的影响。Western blot法检测蛋白和磷酸化蛋白的表达,比色法测定细胞葡萄糖摄取,小干扰RNA敲减p38 MAPK的表达。结果:(1)淫羊藿苷改善高糖对胰岛素刺激的Akt T308磷酸化的不利影响,显著升高Akt T308磷酸化水平,具体表现为,以25、50和75μmol/L的淫羊藿苷处理细胞24 h,可见淫羊藿苷以剂量依赖方式提高Akt T308磷酸化(P0.05或P0.01);而以50μmol/L的淫羊藿苷处理细胞12、24和36 h,可见淫羊藿苷以时间依赖方式提高Akt T308磷酸化(P0.05或P0.01)。此外,淫羊藿苷处理(50μmol/L,24 h)显著提高GLUT4在质膜上的表达和细胞对葡萄糖的摄取(P0.01);(2)高糖作用下,淫羊藿苷可显著提高p38 MAPK蛋白的磷酸化水平(P0.01);(3)高糖作用下,采用特异性抑制剂或基因沉默方法抑制p38 MAPK活性或蛋白表达可显著降低淫羊藿苷对胰岛素刺激的Akt T308磷酸化(P0.01)、GLUT4质膜转位(P0.01)及细胞对葡萄糖摄取的调节作用(P0.05)。结论:淫羊藿苷通过刺激p38 MAPK磷酸化减轻高糖诱导的C2C12肌管细胞胰岛素抵抗。     

淫羊藿苷通过YAP促进大鼠关节软骨细胞增殖的研究

目的 研究淫羊藿苷（Icariin）通过yes相关蛋白（YAP）促进大鼠关节软骨细胞增殖的作用和机制。方法 采用细胞增殖实验、RT-qPCR和免疫荧光染色测定淫羊藿苷促进大鼠关节软骨细胞增殖的作用。采用RT-qPCR检测淫羊藿苷促进YAP表达的作用。通过沉默YAP基因的表达来确定YAP在细胞增殖中的作用以及淫羊藿苷是否通过YAP来促进细胞的增殖。结果 大鼠关节软骨细胞的增殖与YAP表达上调有关。淫羊藿苷能促进YAP表达和去磷酸化,使其进入细胞核内启动增殖相关基因的表达,从而促进软骨细胞增殖。结论 淫羊藿苷通过上调YAP表达以及激活YAP来促进软骨细胞增殖,可能有助于损伤软骨的再生修复。     

基于网络药理学和蛋白模块分析淫羊藿治疗骨关节炎的作用与机制

文题释义：网络药理学：是基于系统生物学的理论,对生物系统的网络分析、选取特定信号节点进行多靶点药物分子设计的新学科。网络药理学强调对信号通路的多途径调节,提高药物的治疗效果,降低毒副作用,从而提高新药临床试验的成功率,节省药物的研发费用。 淫羊藿：为小檗科多年生草本植物,其性温,味辛,归肝经、肾经,传统中医药理论认为淫羊藿具有补肾壮阳、强筋健骨、祛除风湿痹痛等功效,临床上广泛将其应用于骨关节炎疾病的治疗。淫羊藿参与调控骨关节炎的信号通路主要有白细胞介素受体通路、肿瘤坏死因子信号通路、Toll样受体信号通路、T细胞受体信号通路、NF-κB信号通路、破骨细胞分化通路(RANK/RANKL/OPG)。 背景：现代中药药理学研究表明淫羊藿苷在骨关节炎方面有着非常积极的作用。由于淫羊藿所含化学成分较为复杂,且在分子水平上治疗骨关节炎的机制尚不明确,因此利用网络药理学从分子水平来解释淫羊藿治疗骨关节炎的潜在化学成分及作用机制,可为后期药物研发及疾病治疗提供一定理论依据。 目的：采用网络药理学方法探讨淫羊藿治疗骨关节炎的分子机制。 方法：通过TCMSP数据库筛选淫羊藿的药效成分,通过TCMSP、Swiss Target Prediction和STITCH数据库预测淫羊藿药效成分的调控靶点,通过OMIM、GeneCards和TTD数据库预测治疗骨关节炎的靶点,将淫羊藿药效靶点与骨关节炎治疗靶点取交集,得到淫羊藿治疗骨关节炎的靶点,并构建“药物-成分-靶点-疾病”网络。通过STRING数据库分析蛋白互作关系,运用DAVID数据库分析蛋白模块的相关信号通路和功能。 结果与结论：①筛选得到23个淫羊藿药效成分,共预测得到230个淫羊藿药效靶点和1 221个骨关节炎的治疗靶点,取交集后得到95个淫羊藿治疗骨关节炎的靶点,蛋白互作分析提示JUN、AKT1、RELA、MAPK1、IL6、CXCL8、MAPK8、MAPK14、FOS、IL1B为蛋白互作网络中的核心靶点;②关键蛋白模块主要涉及白细胞介素受体通路、肿瘤坏死因子信号通路、Toll样受体信号通路、T细胞受体信号通路、NF-κB信号通路和破骨细胞分化通路,可能通过调控细胞增殖与凋亡、免疫细胞及免疫反应、炎症因子及炎症反应、脂多糖的细胞反应等多种生物过程发挥治疗骨关节炎的作用。 ORCID: 0000-0002-2572-0229(章晓云) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

淫羊藿苷对糖尿病大鼠阴茎组织细胞凋亡及亚硝基谷胱甘肽还原酶表达的影响

目的:探讨淫羊藿苷对糖尿病大鼠阴茎组织细胞凋亡以及亚硝基谷胱甘肽还原酶(GSNOR)表达的影响.方法:采用链尿佐菌素(STZ)建立糖尿病大鼠模型.分为正常对照组、糖尿病模型组、糖尿病淫羊藿苷干预组(高、中、低剂量分别为30、70、100 mg·kg-1·d-1,灌胃,连用21 d).TUNEL法检测阴茎组织细胞凋亡,免疫印迹检测GSNOR表达.结果:淫羊藿苷高、中剂量组阴茎勃起组织细胞凋亡指数降低,与模型组比较差异有统计学意义.淫羊藿苷干预组阴茎组织GSNOR蛋白表达增加,中、高剂量组与模型组比较差异有统计学意义.结论:淫羊藿苷能抑制糖尿病大鼠阴茎组织细胞凋亡并上调GSNOR蛋白表达.     

淫羊藿苷通过下调转移相关蛋白2抑制MGC803细胞的增殖、迁移和侵袭

目的探讨淫羊藿苷是否通过调控转移相关蛋白2(MTA2)表达抑制人胃癌细胞系MGC803细胞增殖、迁移和侵袭及其作用机制。方法以不同浓度淫羊藿苷干预MGC803细胞,MTT法检测细胞活力; Transwell小室法和Western blot分别检测细胞迁移和侵袭及MMP-2、MMP-9和MTA2蛋白表达;将MTA2 siRNA转染至MGC803细胞后检测细胞活力、迁移和侵袭;将pc DNA-MTA2转染至MGC803细胞,联合淫羊藿苷处理,MTT法和Traswell小室法检测细胞活力、迁移和侵袭。结果不同浓度淫羊藿苷均能有效抑制MGC803细胞活力。以200μmol/L淫羊藿苷干预MGC803细胞后,细胞迁移和侵袭能力下降(P0. 05),MMP-2、MMP-9、MTA2蛋白表达下调。敲减MTA2能够抑制细胞活力、迁移和侵袭。过表达MTA2可部分逆转淫羊藿苷对MGC803细胞活力、迁移和侵袭的抑制作用。结论淫羊藿苷能够通过调控MTA2、MMP-2和MMP-9蛋白表达,抑制胃癌细胞增殖、迁移和侵袭。     

骨髓和脂肪来源的间充质干细胞免疫调节作用的比较

目的比较脂肪源间充质干细胞(AMSCs)和骨髓来源间充质干细胞(BMSCs)的免疫调节能力的差异。方法用流式细胞仪分析AMSCs和BMSCs的表型。通过MSCs和淋巴细胞共培养体系,检测MSCs对T细胞增殖、周期、活化、凋亡以及Th细胞分化的影响。结果表型分析结果显示AMSCs和BMSCs的表型基本一致。AMSCs和BMSCs都能抑制T细胞的增殖和早期活化,并在调节辅助性T细胞亚群的分化上作用类似。但在MSC对活化后T细胞的凋亡影响方面,BMSCs能够抑制活化T细胞的凋亡,而AMSC没有这种作用。结论 AMSCs和BMSCs对T淋巴细胞的影响基本类似,其对活化T细胞凋亡影响的差异还有待进一步的机制研究。     

枸杞多糖调控老年大鼠T细胞凋亡及相关基因表达的研究

目的 :探讨枸杞多糖对老年大鼠T细胞过度凋亡及相关基因表达的调节作用。方法 :利用TUNEL标记的流式细胞术和荧光实时定量PCR技术 ,研究了老年大鼠和年轻大鼠T细胞凋亡百分率及抗凋亡和促凋亡基因 (Fas,FasL ,TNFR1,Bax ,Bcl 2 ,TNFR2 )mRNA表达情况 ,并研究了枸杞多糖对老年大鼠T细胞凋亡百分率及促凋亡和抗凋亡基因mRNA表达的影响。结果 :枸杞多糖能够有效地降低老年大鼠T细胞的过度凋亡 ,而且可以下调促凋亡的TNFR1基因mRNA表达并上调抗凋亡的Bcl 2基因mRNA表达。结论 :枸杞多糖下调促凋亡基因表达的同时上调抗凋亡基因的表达 ,从而改善老年大鼠T细胞过度凋亡的状态     

紫杉醇对小鼠T细胞的影响

为研究抗癌药紫杉醇(PTX)对T细胞行为的影响及其分子机制,利用流式细胞术分析多克隆刺激剂ConA刺激下T细胞行为:羧基荧光素乙酰乙酸琥珀酰亚胺酯(CFSE)标记技术分析T细胞增殖相关指数;碘化丙锭染色分析细胞周期分布;AnnexinV-PI染色检测T细胞凋亡;荧光标记的单克隆抗体染色检测T细胞活化表达CD25的百分率。结果显示.PTX对ConA刺激下小鼠T细胞增殖具有明显的抑制作用,且呈剂量依赖性。该浓度范围PTX阻滞T细胞于G2/M期,诱导凋亡及抑制CD25表达。25nmol/L的PTX与10nmol/L的环孢素A(CsA)具有明显的协同抑制效应。以上结果表明PTX可明显抑制多克隆刺激剂ConA诱导的T细胞体外增殖,是G2/M期阻滞、凋亡诱导和CD25表达抑制等多种机制共同作用的结果。     

哮喘小鼠T细胞周期和bcl-2基因表达的测定及其意义

目的 :观察哮喘小鼠T细胞周期和bcl- 2基因表达的变化及地塞米松对它们的影响。方法 :复制小鼠过敏性哮喘动物模型 ,应用流式细胞术观察脾及肺泡灌洗液 (BALF)中T细胞数、T细胞周期和bcl- 2基因表达的变化。结果 :哮喘组脾和BALF中淋巴细胞CD3表达率显著高于对照组 ;哮喘 地塞米松组BALF淋巴细胞中CD3表达降低 ,但脾淋巴细胞中CD3表达增高 ;哮喘组S期及G2 M期细胞数明显多于对照组 ,同时凋亡率也高于对照组 ;哮喘 地塞米松组S期及G2 M期细胞数减少 ,凋亡增多 ;哮喘组T细胞bcl- 2基因表达率显著高于对照组 ,哮喘 地塞米松对bcl- 2基因表达与哮喘组比较无明显变化。结论 :哮喘发病时 ,T细胞增多 ,脾T细胞活化增殖增加 ,凋亡增加 ,同时 ,bcl- 2基因表达率明显增加。地塞米松对哮喘的治疗作用可能并非通过抑制T细胞bcl- 2基因表达的途径。     

Double-blind placebo-controlled challenges for peanut allergy the efficiency of blinding procedures and the allergenic activity of peanut availability in the recipes

Background:  A firm diagnosis of double-blind placebo-controlled food challenge (DBPCFC) would facilitate the diagnosis in patients with uncertain history of reaction. Guidelines are lacking for an upper provoking dose and how to hide high concentrations of peanuts.
Aim:  To develop and evaluate a double-blind recipe with minimum 10% of peanut. To compare the recipe with published recipes regarding blindness, taste, texture and immunoglobulin (Ig)E antibody binding to peanut.
Methods:  A recipe (I) with 10% of peanut was developed evaluated and used in DBPCFC. The challenges were followed by development of a concentrated recipe (II) (15% peanut, 25% fat). Recipe II was compared with the only published recipe (III) (11% peanut, 7% fat) regarding taste, texture and availability of peanut. Recipe IV (12% peanut, 10% fat) was developed using the same methods. The binding of IgE in the recipes was measured using an inhibition method.
Results:  During challenges, one patient reacted after 4 g, emphasizing the need for blinding recipes containing high doses of peanut. Evaluation between recipes II and III, only recipe II was regarded as blind by the taste panels. A tenfold lower availability of peanut protein in the recipe II was found at 50% of inhibition. Recipe IV had a better IgE binding that did not differ from the original peanut extract.
Conclusion:  The peanut taste and texture can be hidden in a challenge medium. The fat content was important for the availability of the allergenic protein in challenges. The availability of allergens must be taken into consideration when used for DBPCFC.     

Genotoxicity, cytotoxicity and gene expression in patients undergoing elective surgery under isoflurane anaesthesia

There are numerous studies reporting on the effects of inhalation anaesthesia in cells of exposed individuals but not much is known about the ability of isoflurane (ISF) to induce oxidative DNA damage. However, surgery is often associated with a temporary perioperative immunological alteration, and some volatile anaesthetics seem to contribute to a transient lymphocytopenia after surgery. We conducted a study to evaluate a possible genotoxic effect, including oxidative DNA damage, and apoptosis in peripheral lymphocytes of 20 patients American Society of Anaesthesiologists physical status I undergoing minor elective surgery lasting at least 120 min, under anaesthesia with ISF. We also investigated the expression of several genes in blood cells. Blood samples were collected at three time points: before anaesthesia (T(1)), 2 h after the beginning of anaesthesia (T(2)) and on the first post-operative day (T(3)). General DNA damage and oxidised bases (Fpg and endo III-sites) in blood lymphocytes were evaluated using the comet assay. Lymphocytes were phenotyped and apoptosis was evaluated by flow cytometry. In addition, expressions of hOGG1 and XRCC1, genes involved in DNA repair, and BCL2, a gene related to apoptosis, were assessed by quantitative real-time polymerase chain reaction. Results showed no statistically significant difference in the level of DNA damage and oxidised bases among the three sampling times. Anaesthesia with ISF did not increase the percentage of cells in early or late apoptosis in cytotoxic or helper T lymphocytes. Lower hOGG1 and BCL2 expressions were detected at T(3) in comparison to the other two previous time points, and there was significantly lower expression of XRCC1 at T(3) in relation to T(2). In conclusion, the exposure to ISF did not result in genotoxicity and cytotoxicity in lymphocytes and in toxicogenomic effect in leukocytes, although DNA repair and apoptosis-related genes were down-regulated on the first post-operative day.     

心理应激对大鼠淋巴细胞凋亡及基因调控的影响

目的：探讨不同心理应激强度对大鼠外周血淋巴细胞凋亡及其调控基因Bcl-2、Bax基因表达的变化。方法：健康的雄性SD大鼠24只，随机分为对照组、中等强度心理应激组、高强度心理应激组，每组8只。分别对大鼠进行3周高、中等强度噪音诱发的心理应激，采用流式细胞仪测定各组淋巴细胞凋亡的情况以及用免疫组织化学法观察调控基因Bcl-2、Bax基因表达的变化。结果：①高强度应激组大鼠淋巴细胞群中存有典型的凋亡细胞，且凋亡细胞发生率明显高于对照组，而中等强度应激组大鼠淋巴细胞凋亡率不显著。②高强度心理应激组大鼠淋巴细胞的Bcl-2表达下调，而Bax的表达量明显增加。结论：高强度心理应激过程中存在着免疫细胞凋亡，而且其发生与相关调控基因的表达一致。     

Morphine promotes apoptosis in Jurkat cells.

Patients with intravenous heroin addiction are prone to recurrent infections and at times these infections are fatal. We evaluated the effect of morphine on the apoptosis of Jurkat cells and freshly isolated human T lymphocytes. Morphine promoted apoptosis of both the Jurkat cells and the freshly isolated T lymphocytes in a dose-dependent manner. DAGO, a specific mu receptor agonist, also promoted Jurkat cell apoptosis. DNA isolated from morphine-treated Jurkat cells and T lymphocytes also showed integer multiples of 200 base pairs. Superoxide dismutase (SOD) enhanced lymphocyte apoptosis; whereas catalase attenuated the morphine-induced apoptosis of Jurkat cells as well as of T lymphocytes. Morphine-treated Jurkat cells also showed a decreased expression of bcl-2 and an enhanced expression of bax. In addition, morphine-treated Jurkat cells showed activation of caspase-3. These results indicate that morphine-induced T lymphocyte apoptosis may be mediated through the generation of reactive oxygen species. The change in ratio of bax and bcl-2 seems to tilt the balance toward apoptosis, leading to the activation of caspase-3. This study provides further support for the hypothesis that morphine may be directly compromising immune function by enhancing apoptosis of T lymphocytes in patients with heroin addiction.     

Large-scale gene expression analysis of osteoblasts cultured on three different Ti-6Al-4V surface treatments

To improve implant biocompatibility, we developed a simple cost-effective thermal surface treatment allowing an increase in the oxide layer thickness of a titanium (Ti) alloy used in orthopaedic implants. The goal of this study was to test in vitro the reaction of osteoblasts to the developed surface treatment and to compare it to the osteoblast reaction to two other surface treatments currently used in the practice of implant surgery. Quantification of osteoblast gene expression on a large scale was used in this study. The kinetics of gene expression over 120 h was followed for 58 genes to quantify the effect of the developed surface treatment. Twenty eight genes were further selected to compare the effects of surface treatments on osteoblasts. Based on the genes studied, we could propose a general pathway for the cell reaction according to the surface treatments used: (1) metal ion release changes the time course of gene expression in the FAK pathway; (2) once the accumulation of metal ions released from the Ti surface exceeds a threshold value, cell growth is diminished and apoptosis may be activated; (3) PTK up-regulation is also induced by metal ion release; (4) the expression of Bcl-2 family and Bax may suggest that metal ions induce apoptosis. The developed treatment seems to increase the Ti-6Al-4V biocompatibility as highlighted by the lower impact of this treatment by the different pathways studied, on the lower inflammatory reaction that could be induced, as well as by the lower induced osteoblast apoptosis compared to the two other surface treatments.