国外期刊摘译

联合应用周期素依赖性蛋白激酶与AKT抑制剂诱导转移性前列腺癌细胞凋亡;肿瘤蛋白D52的表达变化对前列腺癌细胞凋亡与迁移影响的研究;抑制NF-κB与激活AP-1可增强前列腺癌细胞的凋亡;厚朴酚通过抑制EGFR／PI3K／Akt信号通路诱导人前列腺癌细胞凋亡;转移性前列腺癌细胞中PI3K／Akt依赖的转录调控与NF-κB介导的BMP-2-Smad信号通路的激活……     

影响脑胶质瘤预后的关键信号通路调控机制研究进展

脑胶质瘤恶性程度高,复发率高,预后差,对此分析了脑胶质瘤中Hippo/YAP、PI3K/AKT/mTOR、miRNA、WNT/β-catenin、Notch、Hedgehog及TGF-β等信号通路及关键酶的作用机制,得出 YAP1抑制剂可能成为未来治疗脑胶质瘤有效的靶点,抑制PI3K/AKT/mTOR、Shh...     

TSP-1-CD_(47)激活氧化应激与肾脏损伤

正氧化应激是指机体接触各种有害刺激时,体内产生大量的高活性分子,即活性氧自由基(reactive oxygen species,ROS)[1]。大量产生的ROS通过脂质过氧化、损伤DNA和破坏蛋白质等诱发细胞凋亡发生,激活炎症因子、核因子-κB(NF-κB)、TGF-β1等细胞因子和PI3K/Akt、p38、MAPK等信号通路共同损伤肾小球、肾小管间质和血管组织,导致肾小球滤过率增加,     

ERα-AMPK-Sirt1信号通路在骨质疏松症中的作用

近年来,与骨代谢相关的分子信号通路成为研究的热点。其中Wnt/β-catenin信号通路、RANKL/RANK/OPG信号通路、NF-κB信号通路、PPAR-γ信号通路、PTH信号通路、MAPK信号通路、PI3K/Akt信号通路、Hedgehog信号通路和Notch信号通路对骨质疏松症的发病具有重要意义,但目前尚未有关于ERα-AMPK-Sirt1信号通路的研究报道。雌激素受体α(ERα)通过与配体结合、单磷酸腺苷活化蛋白激酶(AMPK)通过磷酸化作用、沉默信息调节因子2相关酶1(Sirt1)通过去乙酰化修饰等共同调控成骨细胞、破骨细胞的功能,且三者之间存在一定的上下游关系;研究表明ERα能够直接增加LKB1启动子的活性,而LKB1是AMPK最主要的上游蛋白激酶,活化的LKB1能够激活AMPK; AMPK可以激活Sirt1,而Sirt1反过来又可以通过磷酸化作用来激活AMPK,二者之间相互作用可参与调控成骨细胞的自噬或凋亡等,以上均提示了ERα-AMPK-Sirt1信号通路在骨质疏松症发病机制中的重要作用,因此有必要对ERα-AMPK-Sirt1信号通路进行深入研究,以便更好地指导临床抗骨质疏松新药物的研发,为临床实践提供更多可靠的偱证医学证据。     

RAS/MAPK/NF-κB信号通路在姜黄素治疗大鼠结肠癌中的作用

目的:研究RAS/MAPK/NF-κB信号通路在姜黄素治疗大鼠结肠癌中的作用和意义。方法:大鼠结肠癌模型构建后,模型组和对照组给予正常饲料喂养,实验组给予0.2%姜黄素固体饲料喂食。HE染色观察结肠组织形态;检测结肠组织内EGFR蛋白;Western blot法和RT-PCR检测K-RAS、p-ERK、NF-κB、EGFR和Caspase 3蛋白含量和mRNA含量的表达。结果:与模型组相比,实验组大鼠结肠内肿瘤数目明显降低,差异有统计学意义(t=6.217,P0.001)。模型组大鼠结肠癌诱癌率为85.00%,实验组大鼠为55.00%,差异有统计学意义(χ~2=4.286,P=0.038)。与对照组相比,模型组和实验组大鼠K-RAS、p-ERK、NF-κB、EGFR和Caspase 3 mRNA和蛋白含量显著升高,差异有统计学意义(P0.05);与模型组相比,实验组大鼠K-RAS、p-ERK、NF-κB、EGFR和Caspase 3 mRNA和蛋白含量显著降低,差异有统计学意义(P0.05)。结论:RAS/MAPK/NF-κB信号通路在姜黄素抑制结肠癌细胞的生长和增殖的过程中发挥重要作用。     

肿瘤多药耐药与细胞信号转导的研究进展

肿瘤多药耐药是肿瘤治疗失败的重要原因,最近研究发现细胞信号转导通路在肿瘤细胞耐药形成的过程中具有重要作用,主要包括凋亡、NF-κB、MAPK、PI3K/Akt通路及肿瘤干细胞等方面,而应用相应的通路阻断剂逆转耐药将成为提高肿瘤治疗效果的亮点。本文主要对以上与肿瘤多药耐药相关的细胞信号转导通路作一综述。     

经线粒体途径相关信号通路对成骨细胞的影响

骨质疏松是骨科的常见病症,是以骨微观结构改变、骨脆性增加、骨量减少为特征的全身代谢性骨质病变。成骨细胞与破骨细胞对骨组织形成、破坏作用的失衡是骨量丢失的主要成因。因此,抑制成骨细胞的凋亡是治疗骨质疏松的关键。现已知,成骨细胞的凋亡主要是由线粒体凋亡途径有关的多种信号通路和多种细胞因子作用导致。本文主要对线粒体凋亡途径及相关信号通路PI3K-Akt、MAPK、Wnt/β-catenin、NF-κB通路和其中的关键靶点作一综述,并阐述部分信号通路之间的作用及其对成骨细胞凋亡的影响,对深入研究骨质疏松的发病机制及研发有关治疗新药有重大意义。     

大黄素对胆管癌QBC939细胞生长及磷酸肌醇3激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路表达的影响

目的 观察大黄素在体外对胆管癌QBC939细胞生长的抑制作用及其对磷酸肌醇3激酶(PI3K)/蛋白激酶B(Akt)/雷帕霉素靶蛋白(mTOR)信号转导通路的影响.方法 用大黄素作为干预因素,时间效应组以含大黄素的培养液分别培养QBC939细胞不同时间,剂量效应组分别用不同浓度大黄素的培养液与QBC939细胞共培养;检测细胞增殖,逆转录-聚合酶链反应(RT-PCR)检测细胞中B淋巴细胞/白血病-2 (bcl-2) mRNA表达,Western blot检测细胞中bcl-2、Akt、磷酸化Akt (p-Akt)、核因子(NF)-κB、磷酸化NF-κB(p-NF-κB)、mTOR、磷酸化mTOR(p-mTOR)蛋白质的表达.结果 10、20、40、80 μmol/L大黄素对QBC939细胞增殖抑制率分别为17.3％、28.6％、46.5％和66.4％ (P ＜0.05),bcl-2、p-Akt、NF-κB、p-NF-κB、mTOR、p-mTOR表达明显下降,Akt表达无变化.结论 大黄素抑制QBC939细胞增殖,可能通过抑制PI3K/Akt/mTOR信号转导途径.     

γ-氨基丁酸B型受体对结肠癌HCT116细胞周期的影响

目的利用人结肠癌细胞株HCT116细胞为研究模型,探究γ-氨基丁酸B型受体（GABABR）/糖原合成激酶3β（GSK-3β）/核转录因子（NF-κB）信号通路对结肠肿瘤细胞HCT116周期的影响,明确GABABR调控结肠癌细胞增殖的机制。 方法使用人结肠癌细胞株HCT116细胞为模型,构建针对GABABR的shRNA,流式细胞仪检测不同刺激条件下HCT116细胞周期分布,四甲基偶氮唑盐微量酶反应比色法（MTT）、5-溴脱氧尿嘧啶核苷（Brdu）法检测细胞的增殖能力变化。 结果GABABR可调控HCT116细胞的增殖。GABABR激动剂巴氯芬将HCT116细胞滞留在G1期,GSK-3β激动剂wort能逆转巴氯芬对结肠癌的该作用;GSK-3β抑制剂SB216763处理后,HCT116细胞增殖得到抑制,而NF-κB激动剂PMA可以阻断此作用;NF-κB激动剂PDTC能够回救敲低GABABR所引起的HCT116细胞增殖抑制,Akt抑制剂MK-2206 2HCl能逆转巴氯芬、SB216763对HCT116细胞增殖的抑制作用。 结论GABABR/GSK-3β/NF-κB信号通路可以调控结肠癌细胞增殖,通过抑制GSK-3β的活性,抑制NF-κB信号通路的激活,将HCT116细胞滞留在G1期。GABABR/GSK-3β/NF-κB信号通路可以作为临床预防和治疗结肠癌的潜在药物靶点之一。     

前列腺癌中TGF-β/Smad信号的研究进展

转移生长因子β(TGF-β)超家族的成员及其下游的Smad信号转导分子与肿瘤的发生与发展有密切关系。在前列腺癌中,TGF-β/Smad信号通路被激活,在细胞水平调节细胞粘附性、肌丝系统、细胞周期等方面,并在分子水平调节特异基因的表达。同时其他的信号通路如MAPK和PI3K/Akt/mTOR通路以及一些基因和蛋白分子对于TGF-β/Smad信号通路的表达也具有调控作用。本文对近年来前列腺癌中关于TGF-β及Smad信号的表达、作用及调控方面的研究进展作一综述,并对其在前列腺癌基础研究与靶点治疗中的意义作一展望。     

Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated with estrogen deficiency by inhibiting the NF-κB and PI3K/Akt signaling pathways

Osteoclasts, the primary bone resorbing cells, are responsible for destructive bone diseases such as postmenopausal osteoporosis, rheumatoid arthritis, and periodontitis. Many plant-derived traditional medicines that might suppress the formation and/or function of osteoclasts are promising treatments for osteoclast-related diseases. In this study, we investigated the effects of leonurine hydrochloride (LH) on receptor activator NF-κB ligand (RANKL)-induced osteoclastogenesis and ovariectomy-induced bone loss. LH is a synthetic chemical compound based on the structure of leonurine, which is found in motherwort and has been reported to exhibit phytoestrogenic activity. In RAW 264.7 cells and mouse bone marrow monocytes (BMMs), LH suppressed RANKL-induced osteoclastogenesis and actin ring formation in a dose-dependent manner. LH targeted RANKL-induced osteoclastogenesis and bone resorption at an early stage. Molecular analysis demonstrated that LH attenuated RANKL-induced NF-κB signaling by inhibiting the phosphorylation and degradation of IκBα and NF-κB p65 nuclear translocation. LH inhibited the RANK-TRAF6 association triggered by RANKL binding and the phosphatidylinositol 3-kinase (PI3K)/Akt axis, without significantly affecting the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and AP-1 signaling pathways. LH attenuated the RANKL-stimulated expression of osteoclast-related genes including NFATc1, tartrate resistant acid phosphatase (TRAP), cathepsin K, and osteoclast-associated receptor (OSCAR). Consistent with the in vitro results, LH administration attenuated osteoclast activity, thus preventing bone loss caused by estrogen deficiency in mice. In this study, LH suppressed RANKL-induced osteoclastogenesis via RANK-TRAF6, NF-κB, and PI3K/Akt signaling. These data provide the first evidence that LH might be a promising therapeutic compound to treat osteoclast-related diseases, such as osteoporosis.     

Prostaglandin D2 induces apoptosis of human osteoclasts through ERK1/2 and Akt signaling pathways

In a recent study we have shown that prostaglandin D₂ (PGD₂) induces human osteoclast (OC) apoptosis through the activation of the chemoattractant receptor homologous molecule expressed on T-helper type 2 cell (CRTH2) receptor and the intrinsic apoptotic pathway. However, the molecular mechanisms underlying this response remain elusive. The objective of this study is to investigate the intracellular signaling pathways mediating PGD₂-induced OC apoptosis. OCs were generated by in vitro differentiation of human peripheral blood mononuclear cells (PBMCs), and then treated with or without the selective inhibitors of mitogen-activated protein kinase-extracellular signal-regulated kinase (ERK) kinase, (MEK)-1/2, phosphatidylinositol3-kinase (PI3K) and NF-κB/IκB kinase-2 (IKK2) prior to the treatments of PGD₂ as well as its agonists and antagonists. Fluorogenic substrate assay and immunoblotting were performed to determine the caspase-3 activity and key proteins involved in Akt, ERK1/2 and NF-κB signaling pathways. Treatments with both PGD₂ and a CRTH2 agonist decreased ERK1/2 (Thr202/Tyr204) and Akt (Ser473) phosphorylation, whereas both treatments increased β-arrestin-1 phosphorylation (Ser412) in the presence of naproxen, which was used to eliminate endogenous prostaglandin production. In the absence of naproxen, treatment with a CRTH2 antagonist increased both ERK1/2 and Akt phosphorylations, and reduced the phosphorylation of β-arrestin-1. Treatment of OCs with a selective MEK-1/2 inhibitor increased caspase-3 activity and OC apoptosis induced by both PGD₂ and a CRTH2 agonist. Moreover, a CRTH2 antagonist diminished the selective MEK-1/2 inhibitor-induced increase in caspase-3 activity in the presence of endogenous prostaglandins. In addition, treatment of OCs with a selective PI3K inhibitor decreased ERK1/2 (Thr202/Tyr204) phosphorylation caused by PGD₂, whereas increased ERK1/2 (Thr202/Tyr204) phosphorylation by a CRTH2 antagonist was attenuated with a PI3K inhibitor treatment. The DP receptor was not implicated in any of the parameters evaluated. Treatment of OCs with PGD₂ as well as its receptor agonists and antagonists did not alter the phosphorylation of RelA/p65 (Ser536). Moreover, the caspase-3 activity was not altered in OCs treated with a selective IKK2/NF-κB inhibitor. In conclusion, endogenous or exogenous PGD₂ induces CRTH2-dependent apoptosis in human differentiated OCs; β-arrestin-1, ERK1/2, and Akt, but not IKK2/NF-κB are probably implicated in the signaling pathways of this receptor in the model studied.     

肾病综合征氧化低密度脂蛋白脂质肾损伤的实验研究

目的 通过观察氧化低密度脂蛋白（oxidized low-density lipoprotein,ox-LDL）对系膜细胞（Mesangial Cells,MCs）分泌炎症介质功能的影响及MAPK信号通路和核因子-κB（nuclear factor kappa B,NF-κB）活性的改变,进一步阐明脂质在肾损伤中的作用机制.方法 利用ox-LDL诱导大鼠系膜细胞增殖,分别采用ELISA、real-time PCR、western blot技术检测MCs炎症介质、MAPK通路相关蛋白（p38、JNK、ERK）及NF-κB的表达水平.结果 利用ox-LDL诱导大鼠系膜细胞增殖并加入CXCR6受体后,其表面炎症因子[CXCL16、CD36、ADAM10、ADAM17、干扰素（IFN）、白细胞介素（IL6）、肿瘤坏死因子（TNF-α）]的表达水平以及MAPK信号通路（p38、JNK、ERK）、NF-κB的磷酸化水平显著升高（P〈0.01）.结论 ox-LDL可促使系膜细胞释放CXCL16、CD36、ADAM10、ADAM17、IFN、IL6、TNF-α等炎症介质,CXCR6可介导这一途径.ox-LDL激活MAPK信号转导通路,使p38、ERK1/2、SAPK/JNK的磷酸化水平升高,激活了NF-κB p65的活性,CXCR6-CXCL16介导MAPK信号途径.     

Restoration of PTEN expression alters the sensitivity of prostate cancer cells to EGFR inhibitors

INTRODUCTION: Prostate cancer (CaP) progression from an androgen-dependent to an androgen-independent state is associated with overexpression of EGFR family members or activation of their downstream signaling pathways, such as PI3K-Akt and MAPK. Although there are data implicating PI3K-Akt or MAPK pathway activation with resistance to EGFR inhibitors in CaP, the potential cross-talk between these pathways in response to EGFR or MAPK inhibitors remains to be examined. METHODS: Cross-talk between PTEN and MAPK signaling and its effects on CaP cell sensitivity to EGFR or MAPK inhibitors were examined in a PTEN-null C4-2 CaP cell, pTetOn PTEN C4-2, where PTEN expression was restored conditionally. RESULTS: Expression of PTEN in C4-2 cells exposed to EGF or serum was associated with increased phospho-ERK levels compared to cells without PTEN expression. Similar hypersensitivity of MAPK signaling was observed when cells were treated with a PI3K inhibitor LY294002. This enhanced sensitivity of MAPK signaling in PTEN-expressing cells was associated with a growth stimulatory effect in response to EGF. Furthermore, EGFR inhibitors gefitinib and lapatinib abrogated hypersensitivity of MAPK signaling and cooperated with PTEN expression to inhibit cell growth in both monolayer and anchorage-independent conditions. Similar cooperative growth inhibition was observed when cells were treated with the MEK inhibitor, CI1040, in combination with PTEN expression suggesting that inhibition of MAPK signaling could mediate the cooperation of EGFR inhibitors with PTEN expression. CONCLUSIONS: Our results suggest that signaling cross-talk between the PI3K-Akt and MAPK pathways occurs in CaP cells, highlighting the potential benefit of targeting both the PI3K-Akt and MAPK pathways in CaP treatment.     

“The Infinite Maze” of breast cancer,signaling pathways and radioresistance

The parallel growth in our understanding of tumor biology and genetics might be the key to understanding local recurrence after optimal treatment is applied. Data suggest that genetic alterations and breast cancer molecular subtypes have an effect on radiotherapy efficacy and that the HER2, EGFR/PI3K/Akt signaling pathways play a pivotal role in modulation of post-irradiation survival. These pathways have been found to be involved in radiosensitivity and/or radioresistance, tumor cell proliferation, and hypoxia. Therefore, affecting the functional activity of key players combined with radiotherapy might be the future of breast irradiation.     

Uric acid induces inflammatory injury in HK-2 cells via PI3K/AKT/NF-κB signaling pathway

Objective To investigate the effects and underlying mechanisms of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/NF-κB signaling pathway in human kidney-2 (HK-2) cells of hyperuricemic nephropathy. Methods HK-2 cells were cultured in vitro and randomly divided into control group and experimental group. The experimental group was induced by high uric acid (720 μmol/L) immersion for 48 h to establish a cell model of hyperuricemic nephropathy in vitro and subsequently divided into hyperuricemic group, overexpressed protease activated receptor 2 (PAR2) and knockdown PAR2 group. The expressions of PAR2, PI3K, AKT, NF-κB mRNA were measured by real-time PCR. The expressions of PAR2, PI3K, AKT and NF-κB protein were measured by Western blotting. The expressions of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), pro-interleukin-1β (pro-IL-1β), interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) were detected by enzyme linked immunosorbent assay (ELISA). Results (1) Compared with the control group, the expressions of PAR2, PI3K, AKT and NF-κB mRNA and protein in hyperuricemic group were significantly increased (all P＜0.05), the expressions of TNF-α, MCP-1, IL-6, pro-IL-1β, IL-1β and TGF-β1 in the supernatant in hyperuricemic group were significantly increased (all P＜0.01). (2) Compared with the hyperuricemic group, the expressions of PAR2, PI3K, AKT and NF-κB mRNA and protein in overexpressed PAR2 group were significantly increased (all P＜0.05), the expressions of TNF-α, MCP-1, IL-6, IL-1β and TGF-β1 in the supernatant were significantly increased (all P＜0.05). (3) Compared with the hyperuricemic group, the expression of PAR2, PI3K, AKT and NF-κB mRNA and protein in knockdown PAR2 group were significantly decreased (all P＜0.05), the expressions of IL-6, pro-IL-1β, IL-1β and TGF-β1 in the supernatant were significantly decreased (all P＜0.05). Conclusions In the process of uric acid-induced HK-2 cell damage, uric acid significantly up-regulates the expression of PI3K/AKT/NF-κB signaling pathway by activating PAR2, leading to a marked increase in inflammatory damage. Knocking down PAR2 inhibits the expression of PI3K/AKT/NF-κB signaling pathway, which can effectively reduce the inflammatory damage of HK-2 cells.     

Anti-inflammation effects of naloxone involve phosphoinositide 3-kinase delta and gamma

Background

Phosphoinositide 3-kinase (PI3K) delta and gamma (the p110δ and p110γ isoforms of PI3K) actively participate in the process of inflammation. We sought to elucidate the possible roles of PI3Kδ and PI3Kγ in mediating the anti-inflammation effects of naloxone.

Materials and methods

Murine macrophages were treated with endotoxin, endotoxin plus naloxone, or endotoxin plus naloxone plus the PI3K inhibitors (the PI3Kδ inhibitor IC87114, the PI3Kγ inhibitor AS252424, or IC87114 plus AS252424) and denoted as the LPS, LPS + N, LPS + N + IC, LPS + N + AS, and LPS + N + IC + AS group, respectively. Differences in inflammatory molecules and levels of nuclear factor-κB (NF-κB) activation and Akt activation (indicator of PI3K activity) among these groups were compared.

Results

The concentrations of inflammatory molecules (macrophage inflammatory protein 2, tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2/prostaglandin E₂) and the levels of NF-κB activation (p-NF-κB p65 and p-inhibitor-κB concentrations and NF-κB-DNA binding activity) of the LPS + N group were significantly lower than those of the LPS group (all P < 0.001). These data confirmed the anti-inflammation effects of naloxone. Moreover, the anti-inflammation effects of naloxone could be counteracted by the inhibitors of PI3Kδ and PI3Kγ, as the concentrations of inflammatory molecules and the levels of NF-κB activation of the LPS + N group were significantly lower than those of the LPS + N + IC, LPS + N + AS, and LPS + N + IC + AS groups (all P < 0.05). In contrast, the concentration of phosphorylated Akt of the LPS + N group was significantly higher than those of the LPS, LPS + N + IC, LPS + N + AS, and LPS + N + IC + AS groups (all P < 0.05).

Conclusions

PI3Kδ and PI3Kγ play crucial roles in mediating the anti-inflammation effects of naloxone.     

WNT5A is induced by inflammatory mediators in bone marrow stromal cells and regulates cytokine and chemokine production

WNT5A has recently been implicated in inflammatory processes, but its role as a bone marrow stromal cell (BMSC)-derived mediator of joint inflammation in arthritis is unclear. Here, we investigated whether inflammatory stimuli induce WNT5A in BMSC to control inflammatory responses. WNT5A levels were determined in human BMSC after stimulation with lipopolysaccharide (LPS) or tumor necrosis factor α (TNF-α,) and in synovial cells and tissue of patients with rheumatoid arthritis (RA) and human TNF-α transgenic (hTNFtg) mice. A microarray analysis of WNT5A-treated murine osteoblasts was performed using Affymetrix gene chips. The regulation of cytokine/chemokine expression was confirmed by qPCR, ELISA, and Luminex technology in BMSC after stimulation with WNT5A or WNT5A knockdown. Relevant signaling pathways were identified using specific inhibitors. Migration of MACS-purified T lymphocytes and monocytes was assessed using the FluoroBlok system. WNT5A expression was increased threefold in BMSC after stimulation with LPS or TNF-α. Synovial fibroblasts from patients with RA showed a twofold increase of WNT5A expression compared with control cells, and its expression was highly induced in the synovial tissue of patients with RA and hTNFtg mice. Microarray analysis of WNT5A-treated osteoblasts identified cytokines and chemokines as targets. The induction of IL-1β, IL-6, CCL2, CCL5, CXCL1, and CXCL5 by WNT5A was confirmed in BMSC and depended on the activation of the NF-κB, mitogen-activated protein (MAPK), and Akt pathways. Accordingly, knockdown of WNT5A markedly reduced the basal and LPS-induced cytokine/chemokine production. Finally, migration of monocytes and T cells toward the supernatant of WNT5A-treated BMSC was increased by 25% and 20%, respectively. This study underlines the critical role of BMSC-derived WNT5A in the regulation of inflammatory processes and suggests its participation in the pathogenesis of RA.     

基于综合生物信息学筛选骨关节炎潜在生物标记物的研究

目的基于基因芯片筛选骨关节炎特征基因谱及信号通路。方法基于Gene Expression Omnibus(GEO)数据库的2个人类关节滑膜组织微阵列(GSE82107和GSE55235),包括20个骨关节炎样本和17个健康对照样本,采用GEO2R工具筛选骨关节炎和健康对照之间的差异表达基因(DEGs)。使用注释、可视化和集成发现数据库进行基因本体论功能(GO)和基于京都基因与基因组百科全书(KEGG)的生物通路富集(https://david.ncifcrf.gov/),以确定DEGs的路径和功能注释。以蛋白-蛋白互作(PPI)基因数据库检索工具为基础,利用Cytoscape软件进行可视化处理(http://www.string-db.org/),分析这些DEGs的PPI,并筛选出关键基因。结果2个微阵列数据库共筛选出滑膜组织191个上调的DEGs和49个下调的DEGs。DEGs主要被富集到"炎症反应"、"骨细胞分化"、"正向凋亡细胞调控"等生物功能调控上以及HTLV-I感染、丝裂原活化蛋白激酶(MAPK)信号通路、甲型流感、肿瘤坏死因子信号通路、NF-κB信号通路、PI3激酶/Akt途径、Toll样受体途径、军团杆菌、沙门氏菌等14条信号通路。PPI在MNC和连接度(Degree)两个模式筛选出前10个关键基因,其中白细胞介素-6、JUN、CXCL8、EGR1、CCND1被确定为有价值的骨关节炎生物标记物。结论通过对骨关节炎的芯片分析筛选出的14条信号通路和10个特征性基因谱,可能为阐明骨关节炎的发病机制提供新的线索。