被动吸烟对大鼠种植体周围组织中OPG和RANKL表达的影响

目的：探讨被动吸烟对大鼠种植体周围骨沉积的影响。方法全麻下在20只Wistar大鼠右侧胫骨内植入纯钛螺纹状种植体,根据是否被动吸烟将大鼠随机分为对照组和被动吸烟组。3个月后,处死动物获取胫骨标本,扫描电镜观察各组种植体周围骨结合情况,采用免疫组织化学方法检测各组种植体周围骨组织中骨保护素（OPG）和核因子κB受体活化因子配体（RANKL）表达水平。结果被动吸烟持续组界面骨表面吸收陷窝增多、增深,骨质沉积降低;RANKL的表达强,范围广泛,颜色深,光密度值（IOD）显著高于对照组（P＜0.05）。OPG的表达弱,均散且染色淡,IOD值明显低于对照组（P＜0.05）。结论被动吸烟可减少大鼠种植体骨界面的骨沉积,机制涉及RANKL的表达水平的升高和OPG表达水平的降低。     

麝香乌龙丸对类风湿关节炎患者血清OPG、RANKL表达的影响

目的:观察麝香乌龙丸对类风湿关节炎(RA)患者血清中骨保护素(OPG)及核因子k B活化因子受体配体(RANKL)水平的影响,从细胞因子角度探讨该药的作用机理。方法 :采用随机分组法将78例类风湿关节炎患者分为治疗组(麝香乌龙丸组)和对照组(白芍总苷胶囊组),治疗程2个月,分别收集2组治疗前后患者血清,运用酶联免疫吸附法(ELISA)检测QPG及RANKL水平变化。结果 :经麝香乌龙丸和白芍总苷胶囊治疗后2组血清OPG均升高,RANKL降低,RANKL/OPG比值降低,治疗组作用较对照组明显(P0.05)。结论 :麝香乌龙丸可以通过抑制患者RANKL水平,升高OPG水平,降低RANKL/OPG比值,延缓骨破坏及促进骨修复,这可能是该药治疗类风湿关节炎的作用机制之一。     

OPG/RANKL/RANK轴在骨相关疾病中的研究现状

OPG/RANKL/RNAK轴作为一个信号转导通路,在许多疾病的发生发展中都具有重要的作用,因此也成为国内外的一个研究热点.各种骨相关性疾病,特别是恶性肿瘤的骨转移导致的骨破坏,是严重影响患者生活质量及生存率的重要因素,OPG/RANKL/RANK轴作为各种导致骨质破坏因素的最终通路,在骨相关疾病的研究中具有重要地位,本文对近几年的相关研究进展做一综述.     

芹菜素调节OPG/RANKL/RANK信号通路对创伤性骨折大鼠骨折愈合的影响

目的 探讨芹菜素对骨保护素(OPG)/核因子κB受体活化因子配体(RANKL)/核因子κB受体活化因子(RANK)信号通路的调控作用及对创伤性骨折大鼠骨折愈合的影响。方法 采用闭合式股骨干骨折术构建创伤性骨折大鼠模型,将造模成功的大鼠随机分为模型组,芹菜素低、中、高剂量组和阳性对照组,每组10只,另取10只健康大鼠作为对照组。各组给予相应干预30 d。采用计算机断层扫描测定大鼠骨小梁密度和厚度,番红O-固绿染色观察大鼠软骨组织病理学变化,酶联免疫吸附试验检测大鼠血清中骨钙素(BGP)、碱性磷酸酶(ALP)、诱导型一氧化氮合酶(iNOS)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6水平,实时荧光定量PCR和蛋白质印迹法检测大鼠股骨组织OPG、RANKL、RANK mRNA和蛋白水平。结果 对照组大鼠软骨组织正常,结构完整;与对照组比较,模型组大鼠软骨组织出现严重损伤,骨小梁密度和厚度、血清BGP、ALP及股骨组织OPG mRNA和蛋白水平降低(P<0.05),血清iNOS、TNF-α、IL-6及股骨组织RANKL、RANK mRNA和蛋白水平升高(P<0.05);...     

血清OPG、RANKL水平与2型糖尿病并发大血管病变的关系分析

目的分析血清骨保护素(OPG)、可溶性核因子κB受体活化因子配体(RANKL)水平与2型糖尿病(T2DM)患者并发大血管病变的关系。方法将该院2014年9月至2017年6月期间收治的120例T2DM患者纳入研究,分为研究组(并发大血管病变,n=45)和对照组(未并发大血管病变,n=75)。检测纳入研究者的颈动脉内膜中层厚度(CIMT)以评估大血管病变程度,检测血清OPG、RANKL及糖化血红蛋白(HbAlC)、C反应蛋白(CRP)、同型半胱氨酸(Hcy)水平,并进行统计学分析。结果研究组左右两侧CIMT均厚于对照组(P0.05);血清OPG、RANKL水平均高于对照组,OPG/RANKL比值低于对照组(P0.05);研究组血清HbAlC、CRP、Hcy水平均高于对照组(P0.05)。Spearman相关系数分析显示,血清OPG、RANKL水平与CIMT、血清HbAlC、CRP、Hcy水平均呈正相关,OPG/RANKL比值与CIMT、血清HbAlC、CRP、Hcy水平呈负相关(P0.05)。结论 T2DM患者血清OPG、RANKL水平及OPG/RANKL比值的显著升高与并发大血管病变密切相关,临床应予以充分重视。     

阿仑磷酸钠对人成骨细胞增殖和护骨素/核因子κB受体活化因子配体mRNA表达的影响

背景:阿仑磷酸钠足新一代的二磷酸盐,属第2代骨质疏松药,临床上广泛用于治疗骨吸收增加类疾病.目的:观察阿仑磷酸钠对人成骨细胞增殖和核因子κB受体活化因子配体(RANKL)及护骨素(OPG)mRNA表达的影响.设计、时间及地点:单一样本观察,于2007-11/2008-03在重庆医科大学基础研究所完成.材料:成骨细胞来源于手术中取得的松质骨骨块;阿仑磷酸钠为杭州默沙东制药有限公司生产,批号:06130.方法:在含1×10-9,1×10-8,1×10-7,1×10-6,1×10-5,1×10-4mol/L不同浓度的阿仑磷酸钠培养液中培养成骨细胞,以不加阿仑磷酸钠培养为对照.主要观察指标:①成骨细胞观察.②以四甲基偶氮唑盐检测阿仑磷酸钠对成骨细胞的增殖的影响.③以半定量反转录-聚合酶链反应方法观察不同浓度阿仑磷酸钠对成骨细胞表达OPG/RANKL mRNA的影响.结果:1×10-5,1 ×10-4mol/L的阿仑磷酸钠抑制成骨细胞增殖,1×109～10-6mol/L的阿仑磷酸钠促进成骨细胞增殖,其中1 ×108mol/L的阿仑磷酸钠对成骨细胞的增殖作用最强.阿仑磷酸钠呈浓度依赖性降低RANKL mRNA表达,干预72 h,1 ×10-5mol/L抑制作用最大(P<0.01).阿仑磷酸钠呈浓度依赖性增加护骨素mRNA表达,干预72 h,1×10-6mol/L增加作用最明显(P<0.01),而1×10-5mol/L时又减低.结论:阿仑磷酸钠能使成骨细胞增殖,1×10-8mol/L浓度增殖作用最强,其可能通过调节OPG/RANKL mRNA表达而影响骨代谢.     

RANKL/OPG体系与骨髓瘤骨病

骨髓瘤骨病(MBD)是多发性骨髓瘤(MM)的重要病理改变之一,也是MM的主要死亡原因之一,研究其发病机理具有重要的临床意义。RANKL即NF-κB受体活化因子配体,是最近发现的一个破骨细胞刺激因子,骨保护索即OPG,是其天然抑制剂。本文就此体系的结构、分布、基本功能及在MBD中的作用进行综述。     

补骨脂素干预大鼠成骨细胞骨保护素/核因子kB受体激活因子配体mRNA的表达

背景:补骨脂素有促进大鼠成骨细胞增殖与分化的作用,但其作用机制尚不明确.目的:探讨补骨脂素对大鼠成骨细胞中骨保护索(osteopomgeterin,OPG)和核因子kB受体激活因子配体(receptor activator nuclear factor kappa b ligand,RANKL)mRNA表达的影响.方法:取第3代生长状况良好的出生24 h内的SD大鼠成骨细胞,补骨脂素组加入1×10-7 mol/L的补骨脂素,雌二醇组加入1×107 mol/L的雌二醇,对照组正常培养.给药72 h后提取细胞总RNA,RT-PCR方法分析细胞OPG/RANKL mRNA的表达.结果与结论:与对照组比较,补骨脂素组和雌二醇组OPG mRNA的表达均明显增加(P＜0.05),而RANKL mRNA的表达明显下降(P＜0.05),但补骨脂索组成骨细胞OPG mRNA的表达较雌二醇组弱(P＜0.05),VOPG/VRANKL 比值也较雌二醇组小(P＜0.05).说明补骨脂素可能通过增加成骨细胞OPG的表达,抑制RANKL的表达来抑制破骨细胞的分化和成熟,从而抑制骨吸收,达到防治骨质疏松症的日的,但作用不如雌二醇明显.     

纤维调节素对大鼠正畸牙牙周组织破骨细胞分化因子表达的影响及相关机制

目的 探讨纤维调节素对大鼠正畸牙牙周组织破骨细胞分化因子表达的影响及相关机制.方法 大鼠正畸牙的牙周膜干细胞(PDLSC)按随机数字表法平分为3组-对照组、纤维调节素1组、纤维调节素2组,分别用0、1、10μg/mL纤维调节素的处理6、12 h.四甲基偶氮唑蓝(MTT)法检测细胞增殖,酶联免疫吸附实验法检测白细胞介素-...     

雌激素对去卵巢鼠OPG,RANKL和ApoE的影响

目的观察雌激素对去卵巢C57BL／6J小鼠股骨内OPG、RAN和ApoE的影响方法采用双侧卵巢切除术制备骨质疏松的动物模型，1w后雌激素替代组开始每周腹腔注射苯甲酸雌二醇（EB）2次，假手术对照组和模型组均注射同等量的橄榄油，至第6周末。6w后应用HE染色和原位杂交法观察各组小鼠股骨内OPG、RANKL、ApoE的变化。结果去卵巢组股骨内OPG、RANKL和ApoE表达与对照组相比明显下降，而补充雌激素后OPG、RANKL和ApoE的表达明显上升。结论说明雌激素可通过增加股骨中OPG、RANKL和ApoE的表达，抗骨质疏松。     

TGF-β和ERK在骨质疏松大鼠骨组织中的表达

目的:研究转化生长因子(TGF-β)和信号调节激酶(ERK)在去卵巢大鼠骨组织中的表达及意义。方法:30只2月龄SD雌性大鼠分别造模为假手术组(SHAM组)、卵巢切除组(OVX组)及雌激素替代组(OVX-N组)各10只,用免疫组化法测定成骨细胞中TGF-β和磷酸化ERK的表达并进行定量分析。结果:TGF-β蛋白阳性表达主要在成骨细胞的胞膜上和胞浆内,ERK主要在成骨细胞核内,OVX-N组TGF-β和ERK的阳性表达高于OVX组(P<0.01,0.05),与SHAM组比较差异不明显。结论:TGF-β和ERK可能在绝经后骨质疏松症中起重要调节作用。     

High levels of synovial fluid osteoprotegerin (OPG) and increased serum ratio of receptor activator of nuclear factor-kappa B ligand (RANKL) to OPG correlate with disease severity in patients with primary knee osteoarthritis

ObjectiveEvaluation of serum and synovial fluid OPG and sRANKL in 37 patients with primary knee osteoarthritis.Design and methodOPG and sRANKL were measured using ELISA.ResultsOPG, sRANKL and sRANKL/OPG were increased in osteoarthritis patients' serum. Synovial OPG was higher than serum OPG, while sRANKL/OPG was higher in the serum; both correlated with disease severity.DiscussionRANKL/OPG pathway is implicated in the pathogenesis of knee osteoarthritis being a suitable target for therapeutic intervention.     

早期干预对宫内感染致脑损伤仔鼠脑组织NB-3表达的影响

目的探讨早期干预对仔鼠脑组织NB-3的表达及其运动功能的影响。方法孕17~18 d Wistar大鼠45只腹腔注射脂多糖(LPS)380μg/kg连续2 d(LPS组),另15只注射同等剂量的无菌生理盐水(NS组)。随机选取LPS组仔鼠80只,分为干预组40只(I组)和非干预组40只(NI组);随机选取NS组仔鼠40只为对照组。早期干预措施主要给予早期触摸与丰富康复训练。仔鼠出生后24 h内在LPS组和NS组随机取5只行脑组织HE染色。其余大鼠分别于出生后14 d、28 d行悬吊试验,1 d、7 d、14 d、21 d、28 d行脑组织免疫组织化学染色,观察NB-3的表达。结果脑组织NB-3的表达及悬吊试验评分三组间均有非常高度显著性差异(P<0.001)。结论宫内感染可致脑损伤鼠NB-3表达增加,早期干预使脑损伤鼠NB-3表达持续增加,并改善其运动功能。     

BMSCS靶向移植联合辛伐他汀对骨质疏松大鼠治疗效果的研究

目的探讨骨髓间充质干细胞(BMSCs)靶向移植联合辛伐他汀治疗骨质疏松症大鼠的治疗效果。方法以切除卵巢的雌性去势骨质疏松大鼠为模型,建立A组(对照组)、B组(模型组)、C组(BMSCs组)、D组(辛伐他汀组)、E组(BMSCs联合辛伐他汀组),饲养12天后,骨密度仪测定各组大鼠骨密度(BMD),ELISA法测定各组血清中骨钙素(BGP)、骨保护素(OPG)、骨保护素配体(OPGL)含量,Western blot检测各组大鼠细胞中BMP-2的蛋白表达水平。结果C、D、E组与A、B组大鼠相比,组织学观察间质中毛细血管内皮增生,均有较多的新骨形成;B组的骨体积分数、类骨质体积分数、矿化沉积率及BMD较A组均显著降低(P0.05),血清中BGP、OPG和OPGL较A组均显著升高(P0.05)。C、D、E组相对于B组在骨体积分数、类骨质体积分数、矿化沉积率及BMD上均显著提升(P0.05),血清中BGP、OPG和OPGL均显著下降(P0.05),E组提升最明显,与两组单纯用药组差异性显著(P0.05)。结论单独应用BMSCs靶向移植和辛伐他汀对鼠骨髓损伤再生和修复有一定治疗作用,两种药物联合使用效果更加明显。     

Maintained malnutrition produces a progressive decrease in (OPG)/RANKL ratio and leptin levels in patients with anorexia nervosa

Objective. Osteoprotegerin (OPG) and receptor activator of nuclear factor‐κB ligand (RANKL) are key factors in bone remodeling in patients with anorexia nervosa (AN) and osteopenia. The purpose of this study was to investigate basal serum levels of OPG, RANKL and leptin, as well as bone mineral density (BMD) measured by DEXA at lumbar vertebrae L1–L4, and their evolution during one year in two groups of patients with AN. Material and methods. Group I included 10 adolescent girls suffering from malnutrition and secondary amenorrhea with an evolution of more than one year at the beginning of the study who received oral estrogen treatment throughout the follow‐up period. Group II comprised 10 girls with malnutrition and secondary amenorrhea with an evolution of less than one year who received nutritional treatment only. All parameters were compared with those of a control group of 19 healthy, age‐matched girls with normal BMI and regular menstrual cycles. Results. The OPG/RANKL ratio was significantly decreased (p<0.05) after 1 year in group I, a fact that was due to an increase (p<0.05) in serum RANKL values. A correlation between OPG/RANKL and BMD was found in group I at the beginning of the study (r = 0.95; p<0.001). Patients in this group showed lower BMD values (p<0.01), both at diagnosis and at the end of the study, than those of group II patients, who showed normal BMD values. Conclusion. The decrease in the OPG/RANKL ratio in girls with AN could partly explain the increase in bone loss that occurs in these patients.     

Maintained malnutrition produces a progressive decrease in (OPG)/RANKL ratio and leptin levels in patients with anorexia nervosa

OBJECTIVE: Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) are key factors in bone remodeling in patients with anorexia nervosa (AN) and osteopenia. The purpose of this study was to investigate basal serum levels of OPG, RANKL and leptin, as well as bone mineral density (BMD) measured by DEXA at lumbar vertebrae L1-L4, and their evolution during one year in two groups of patients with AN. MATERIAL AND METHODS: Group I included 10 adolescent girls suffering from malnutrition and secondary amenorrhea with an evolution of more than one year at the beginning of the study who received oral estrogen treatment throughout the follow-up period. Group II comprised 10 girls with malnutrition and secondary amenorrhea with an evolution of less than one year who received nutritional treatment only. All parameters were compared with those of a control group of 19 healthy, age-matched girls with normal BMI and regular menstrual cycles. RESULTS: The OPG/RANKL ratio was significantly decreased (p<0.05) after 1 year in group I, a fact that was due to an increase (p<0.05) in serum RANKL values. A correlation between OPG/RANKL and BMD was found in group I at the beginning of the study (r = 0.95; p<0.001). Patients in this group showed lower BMD values (p<0.01), both at diagnosis and at the end of the study, than those of group II patients, who showed normal BMD values. CONCLUSION: The decrease in the OPG/RANKL ratio in girls with AN could partly explain the increase in bone loss that occurs in these patients.     

松郁安神方对PCPA致失眠大鼠睡眠时相的影响

目的:观察松郁安神方对失眠大鼠睡眠时相的影响.方法:采用腹腔注射对氯苯丙氨酸(Para-chlorophenylalanine,PCPA)建立失眠大鼠模型,用松郁安神方进行干预,通过动物睡眠生物解析系统,记录脑电(Electroencephalogram,EEG)和肌电(Electromyogram,EMG),分析睡眠...     

Alteration of bone cell function by RANKL and OPG in different in vitro models

BACKGROUND: Receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) are well-documented potent regulators of osteoclast development. However, their effects in mature bone cells and in organ cultures have not been well studied. It is uncertain whether their activities in different experimental models are comparable. MATERIALS AND METHODS: RANKL and OPG were evaluated for their activities in mouse calvarial organ cultures, mouse bone marrow cultures, isolated rat mature osteoclast assays and rat primary osteoblast cultures. Results In murine calvarial organ culture, both muRANKL (> or = 10 ng mL(-1)) and rRANKL (> or = 100 ng mL(-1)) significantly stimulated (45)Ca release, while OPG (> or = 50 ng mL(-1)) was an inhibitor of bone resorption. Meanwhile, [(3)H]-thymidine incorporation in this assay was also modulated (indicating proliferation increases in the osteoblast lineage of cells) although these peptides had no direct effect on [(3)H]-thymidine incorporation in isolated osteoblast assays. In mouse bone marrow cultures, muRANKL (> or = 1 ng mL(-1)) and rRANKL (> or = 5 ng mL(-1)) significantly stimulated osteoclastogenesis. The number of nuclei per osteoclast was also significantly increased. OPG strongly inhibited this index, with over 90% suppression at 1 ng mL(-1). Both muRANKL (10 ng mL(-1)) and rRANKL (100 ng mL(-1)) stimulated, while OPG (10 ng mL(-1)) inhibited osteoclast activity in isolated mature osteoclast assays. CONCLUSION: The current study demonstrated that bone resorption modulated by RANKL and OPG, in murine calvarial organ culture, leads to changes in osteoblast proliferation, suggesting a feedback mechanism from osteoclasts to osteoblasts. In addition, it was found that RANKL and OPG have more potent effects on osteoclastogenesis than on the activity of mature osteoclasts.