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1.
破骨细胞和成骨细胞分别介导骨的吸收过程和合成过程,而OPG、RANK、RANKL在调节二者的比例中发挥非常重要的作用.RANKL与RANK结合后可能通过三种途径:JNK途径、NF-κB途径和蛋白激酶B途径参与破骨细胞的分化,促进骨质的吸收;RANKL与OPG结合后能阻断RANKL与RANK的结合,由于缺乏RANKL-RANK产生的转录活化信号,破骨细胞分化成熟发生障碍,骨质的吸收受到抑制.OPG、RANK、RANKL同时也是免疫分子,在淋巴细胞、淋巴器官的分化、发育中起重要的作用,骨疾病与免疫系统之间存在着一定的关系.RANMKL/RANK与RANKI/OPG在生物体内保持着一定的比率,如果比率失衡,就会引起各种骨疾病.本篇综述总结了近年来OPG、RANK、RANKL结构、作用的新进展以及它们在骨疾病中的作用.  相似文献   

2.
骨质疏松是严重威胁中老年人健康的骨科常见病,OPG/RANK/RANKL是参与调节骨重建的最重要的分子系统之一,与骨疾病相关的骨质疏松有密切联系,并已成为药物设计的新靶点.因此,对该系统的深入研究将为骨生理、病理机制阐明及骨疾病防治带来积极影响.  相似文献   

3.
采用RT-PCR法得到人OPG的编码区cDNA,克隆至穿梭质粒pShuttle,构建重组有OPG编码区cDNA的腺病毒DNA,经Pac I 酶切线性化,在脂质体介导下转染HEK293细胞,制备重组腺病毒并测定病毒滴度约为5×106~1.5×107 pfu/mL。体外感染小鼠成肌细胞C2C12,Western blot及ELISA检测证实有OPG蛋白的表达,并可在细胞培养上清中持续表达6周。感染OPG重组腺病毒的C2C12细胞生长状态良好、细胞周期无明显变化。将重组腺病毒加入体外培养的小鼠骨髓细胞的培养基中,诱导形成的破骨细胞数量及在象牙片上形成的吸收陷窝的数量显著减少(P<0.01)。  相似文献   

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核因子-κB受体活化因子配体(receptor activator of nuclear factor-kappa B ligand,RANKL)/核因子-κB受体活化因子(receptor activator of nuclear factor kappa B,RANK)/骨保护素(osteoprotegerin,OPG)信号通路是调节骨代谢过程中破骨细胞功能的重要通路。OPG能够与RANKL结合并阻止其与RANK结合,抑制破骨细胞生成从而抑制骨吸收,增加骨密度,改善骨质疏松。其中,RANKL/OPG的比值是骨吸收和骨形成平衡的关键。目前血管钙化已不再被看作是单纯的钙磷的被动沉积,而是由血管平滑肌细胞和内皮细胞主动参与的一种与骨形成相似的病理生理过程。在这个过程中,RANKL/RANK/OPG信号通路也起到重要作用。本文就RANKL/RANK/OPG信号通路在骨代谢和血管钙化中的作用机制进行了综述。  相似文献   

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骨是一种动态更新的组织,它不断进行骨吸收(bone resorption)与骨形成(bone formation)的平衡,这个过程称之为骨重建(bone remodeling).核因子κB受体活化因子配体(receptor activator of nuclear factor κB ligand,RANKL)是骨吸收和骨形成耦联的关键,具有诱导破骨细胞(osteoclast, OC)生成、活化,抑制破骨细胞凋亡的作用.RANKL最初发现于活化的T细胞,但骨重建过程中RANKL主要来源于骨细胞、成骨细胞和骨髓基质细胞.RANKL/核因子κB受体活化因子(receptor activator of nuclear factor κB,RANK)/骨保护素(osteoprotegerin, OPG)信号通路在成骨细胞调控破骨细胞生成的过程中起着重要的调节作用,是维持骨重建平衡的关键.本文就RANKL及其在骨中的分子作用机制作一综述.  相似文献   

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目的:观察仙灵骨葆治疗骨质疏松模型大鼠后,对大鼠体内OPG/RANKL/RANK表达的影响。方法:卵巢摘除法建立SD大鼠骨质疏松模型,设立假手术组、对照组(单纯去卵巢组)、雌激素组(给予17β-雌二醇)和治疗组(给予仙灵骨葆)。术后1周开始给药,给药12周后检测各组大鼠股骨骨密度,ELISA法检测血清中OPG/RANKL含量,RT-PCR检测骨组织中OPG/RANK/RAN-KL mRNA表达,免疫组化检测骨组织中RANK的表达。结果:对照组大鼠骨密度显著低于假手术组;治疗组和雌激素组大鼠O-PG表达显著高于对照组,RANK及RANKL的表达显著低于对照组。结论:采用卵巢摘除法成功建立大鼠骨质疏松模型;仙灵骨葆可促进骨质疏松大鼠OPG的表达,并抑制RANK及RANKL的表达,对骨质疏松模型大鼠有治疗作用。  相似文献   

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破骨细胞是一种多核的,具有骨吸收功能的骨组织细胞,在骨吸收过程中起着至关重要的作用.破骨细胞骨吸收功能的异常会引发一系列的临床病症,如骨质疏松症、关节置换术后假体松动、骨硬化症和牙周病变等.破骨细胞骨吸收功能的进一步研究对于各类骨疾病的防治具有重要的意义.然而破骨细胞骨吸收功能的检测方法一直以来是制约破骨细胞研究的瓶颈之一.为此,围绕破骨细胞骨吸收功能的检测方法做一综述.  相似文献   

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目的:研究丹参素对RANKL诱导的破骨细胞分化的影响。方法:运用冲洗法从股骨、胫骨中获得小鼠骨髓源性单核巨噬细胞用于体外RANKL 诱导的破骨细胞分化,同时,施加不同剂量的丹参素干预,经TRAP染色法在形态学上观察观,蛋白印迹法检测蛋白水平的变化,实时定量PCR 检测mRNA 水平变化来研究丹参素对RANKL诱导的骨髓源单核巨噬细胞破骨分化的影响。结果:①不同剂量丹参素干预组与对照组相比,TRAP 阳性破骨细胞数量得到了明显抑制(P<0.05)。②不同剂量丹参素干预组与对照组相比,磷酸化Akt的上调量被明显的降低。磷酸化p38 MAPK,JNK和ERK 的变化则不明显。③不同剂量丹参素干预组与对照组相比,c-fos,TRAP,CTSK 等参与破骨细胞分化的重要基因表达减少,NFATc1 变化不明显。结论:丹参素通过下调磷酸化Akt水平的途径抑制了RANKL诱导的破骨细胞分化。  相似文献   

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目的:观察钛颗粒对小鼠颅骨中OPG/RANKL mRNA及其蛋白表达的影响,探讨关节置换术后骨溶解的发生机制。方法:取成年BALB/C小鼠40只,随机分为假手术组、钛颗粒低剂量组、钛颗粒中剂量组及高剂量组,每组10只。除假手术组外,其余各组分别将钛颗粒15、30、60 mg涂抹于小鼠颅骨表面后缝合切口。8周后取颅骨组织及外周血,运用real-time PCR及ELISA技术测定OPG/RANKL基因及蛋白表达情况。结果:与假手术组相比,钛颗粒低剂量组外周血中OPG蛋白表达及颅骨组织中OPG mRNA的表达均显著上升(P0.01),外周血中RANKL蛋白表达降低,但无统计学差异,颅骨组织中RANKL mRNA表达无显著差异;中剂量组及高剂量组外周血中OPG蛋白表达显著降低(p0.01),RANKL蛋白表达显著升高(P0.01),OPG mRNA表达显著降低(P0.01),RANKL mRNA表达显著升高(P0.01)。低中高三种不同剂量钛颗粒组组间相比,外周血中OPG、RAKNL蛋白及颅骨组织中其mRNA表达均存在明显差异(P0.01),高剂量组对OPG、RANKL蛋白及mRNA表达的影响更显著。结论:钛颗粒可以改变OPG/RANKL的mRNA及蛋白表达量,这可能是其导致关节置换术后体骨溶解进而产生松动的原因之一。  相似文献   

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目的:探讨巴戟天及多糖提取物对成骨细胞骨保护素(OPG)/核因子κB受体活化因子配体(RANKL)基因系统表达的影响。方法:取2~3天的SD大鼠5只分离原代成骨细胞,再取8周龄SD大鼠35只随机分为七组,对照组不进行处理,三组给予10 g/L、50 g/L、100 g/L巴戟天水灌胃,其余三组分别给予10 g/L、50 g/L、100 g/L巴戟天多糖灌胃,72 h后采用采用ELISA法测定培养液中OPG、RANKL及骨钙素的含量,采用MTT法检测不同浓度巴戟天水及多糖提取物对大鼠成骨细胞增殖的影响,采用荧光定量PCR检测OPG和RANKL mRNA表达情况;通过Westernblot检测OPG和RANKL蛋白表达水平。结果:巴戟天水及多糖提取物组A570nm、ALP活性、骨钙素含量、OPG/RANKL mRNA表达量、OPG和RANKL蛋白表达阳性密度均高于对照组(P0.05);A 570 nm、ALP活性、骨钙素含量、OPG/RANKL mRNA表达量、OPG和RANKL蛋白表达阳性密度均高于同等剂量的水提取物各组(P0.05);巴戟天多糖组中随着多糖剂量的升高A 570 nm、ALP活性、骨钙素含量、OPG/RANKL mRNA表达量、OPG和RANKL蛋白表达阳性密度,差异比较有统计学意义(P0.05)。结论:巴戟天水及多糖提取物均能促进体外培养成骨细胞的增殖,提高成骨细胞活性。  相似文献   

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The dynamic balance between bone formation and bone resorption is vital for the retention of bone mass. The abnormal activation of osteoclasts, unique cells that degrade the bone matrix, may result in many bone diseases such as osteoporosis. Osteoporosis, a bone metabolism disease, occurs when extreme osteoclast-mediated bone resorption outstrips osteoblast-related bone synthesis. Therefore, it is of great interest to identify agents that can regulate the activity of osteoclasts and prevent bone loss-induced bone diseases. In this study, we found that N-[2-(4-benzoyl-1-piperazinyl)phenyl]-2-(4-chlorophenoxy) acetamide (PPOAC-Bz) exerted a strong inhibitory effect on osteoclastogenesis. PPOAC-Bz altered the mRNA expressions of several osteoclast-specific marker genes and blocked the formation of mature osteoclasts, suppressing F-actin belt formation and bone resorption activity in vitro. In addition, PPOAC-Bz prevented OVX-induced bone loss in vivo. These findings highlighted the potential of PPOAC-Bz as a prospective drug for the treatment of osteolytic disorders.  相似文献   

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Osteoclast (OC) is the only cell involved in bone resorption. Dysfunction of OCs leads to a variety of bone diseases. Ligustilide (LIG) is the main component of the volatile oil isolated and purified from Angelica sinensis. LIG exerts many pharmacological activities, but its effects on osteoclastogenesis and bone resorption are still unclear. Our study showed that LIG inhibited receptor activator of nuclear factor-κB (NF-κB) ligand-induced OC formation and activation in a dose-dependent manner. Additionally, LIG downregulated the messenger RNA (mRNA) expression of OC-specific genes, such as V-ATPase d2, tartrate-resistant acid phosphatase, a dendritic cell-specific transmembrane protein, cathepsin K, and nuclear factor of activated T cells cl. Furthermore, LIG blocked the activation of NF-κB/extracellular signal-regulated kinase/p38/immunoreceptor tyrosine-based activation motif signaling pathways. Crucially, the expression of tumor necrosis factor receptor-associated factor 6 proteins and the expression of receptor activator of NF-κB mRNA were inhibited by LIG. However, LIG did not affect the formation and mineralization of osteoblasts. Collectively, this observation suggests that LIG may serve as a promising agent for the prevention and treatment of diseases caused by abnormal bone resorption.  相似文献   

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Postmenopausal women undergo rapid bone loss, which caused by the accelerated osteoclastic bone resorption. Receptor activator of nuclear factor kappa-B ligand (RANKL) plays critical and essential roles on varied stages of osteoclastogenesis. Oleanolic acid (OA), a naturally derived small compound, has been found suppress osteoclastogenesis in early stage of bone marrow macrophages (BMMs). However, whether OA also regulates the late stage of osteoclastogenesis remains unclear. Here, the regulatory effect of OA on the late stage of osteoclastogenesis was investigated in vitro using RANKL-pretreated BMMs and in vivo using osteoprotegerin (OPG) knockout mice. Our in vitro studies demonstrate that OA inhibits the late stage of osteoclastogenesis from RANKL-pretreated BMMs. For in vivo animal investigation, OA attenuates the bone loss phenotypes in OPG-knockout mice by decreasing the densities of osteoclast, which are in consistent with the finding with in vitro osteoclastogenesis. Mechanistic investigations found that OA largely inhibit the activity of c-Fos and Nuclear factor of activated T-cells c1 (NFATc1) with RANKL-pretreated BMMs and OPG-knockout mice. Furthermore, OA suppresses the activities of osteoclast genes, such as Tartrate resistant acid phosphatase (TRAP), CathepsinK (Ctsk), and Matrix metalloproteinase 9 (MMP9). Taken together these findings, they have not only defined an inhibitory effect of OA in the late stage of osteoclastogenesis but have also gained new molecular mechanisms underlying the process of osteoclast formation.  相似文献   

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PCR扩增OPG-HSP65基因,构建原核重组表达载体pET-28a-OPG-HSP65,转化大肠杆菌BL21(DE3),经IPTG诱导表达产生包涵体形式的目的蛋白。对重组蛋白进行Western blot检测表明,重组蛋白能与抗His-Tag单克隆抗体及鼠抗人OPG单克隆抗体特异性结合。对重组蛋白进行尿素洗涤纯化,进而透析、复性。经破骨细胞生长抑制实验和抑炎实验表明,重组蛋白能减少破骨细胞生成及减轻迟发型超敏反应小鼠模型炎症反应。  相似文献   

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Osteolytic bone diseases such as osteoporosis have a common pathological feature in which osteoclastic bone resorption outstrips bone synthesis. Osteoclast formation and activation are regulated by receptor activator of nuclear factor κB ligand (RANKL). The induction of RANKL‐signaling pathways occurs following the interaction of RANKL to its cognate receptor, RANK. This specific binding drives the activation of downstream signaling pathways; which ultimately induce the formation and activation of osteoclasts. In this study, we showed that a natural immunomodulator, mangiferin, inhibits osteoclast formation and bone resorption by attenuating RANKL‐induced signaling. Mangiferin diminished the expression of osteoclast marker genes, including cathepsin K, calcitonin receptor, DC‐STAMP, and V‐ATPase d2. Mechanistic studies revealed that mangiferin inhibits RANKL‐induced activation of NF‐κB, concomitant with the inhibition of IκB‐α degradation, and p65 nuclear translocation. In addition, mangiferin also exhibited an inhibitory effect on RANKL‐induced ERK phosphorylation. Collectively, our data demonstrates that mangiferin exhibits anti‐resorptive properties, suggesting the potential application of mangiferin for the treatment and prevention of bone diseases involving excessive osteoclastic bone resorption. J. Cell. Biochem. 112: 89–97, 2011. © 2010 Wiley‐Liss, Inc.  相似文献   

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