淫羊藿总黄酮对去卵巢大鼠骨组织OPG、 OPGL mRNA表达的影响

目的：探讨淫羊藿总黄酮（totalflavoneofepimedium,TFE）治疗骨质疏松症的分子机制,为传统中药的现代化和二次开发提供实验依据。方法：将60只4月龄健康雌性SD大鼠按随机数字表法分为对照组（A组,20只,行假手术处理）,去卵巢纽（OVX组,20只,切除卵巢后不给予淫羊藿处理）,淫羊藿组（TFE纽,20只,切除卵巢后给予淫羊藿灌胃）。所有大鼠术前及术后4周以DEXA骨密度仪检测L4骨密度变化（若BMD下降〉20％,则骨质疏松模型建立）。模型建立后TFE组大鼠给予淫羊藿总黄酮（浓度30mg／ml,10ml／kg,1次／d）灌胃4周。所有大鼠处死前再行DEXA骨密度检测,过量麻醉法处死后取其股骨下部,切片匀浆提取骨组织中RNA,应用逆转录一聚合酶链反应（RT—PCR）技术检测骨组织护骨素（osteoprotegrin,OPG）、护骨素配体（0PGL）mRNA的表达。结果：①TFE组大鼠切除卵巢4周后,腰椎BMD均值降至（0．084±0．020）g／cm^2,降幅〉20％证明骨质疏松模型建立。TFE灌胃4周后其腰椎BMD提高至（0．112±0．009）g／cm^2,与给药前比较有明显改善,差异有统计学意义（P〈0．05）;②TFE组大鼠骨组织中OPGmR—NA的表达较OVX组相比,明显增强,且有统计学差异（P〈0．05）,但对OPGLmRNA表达促进作用不明显,组间无统计学差异（P〉0．05）。结论：TFE是通过促进骨组织中OPGmRNA的表达来抑制破骨细胞的分化和成熟,从而达到治疗骨质疏松症的目的。     

Elevated serum receptor activator of NFκB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase (MMP)3, and ProMMP1 in patients with juvenile idiopathic arthritis

We studied the serum levels of receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), pro-matrix metalloproteinase (MMP) 1, MMP3, and tissue inhibitor of metalloproteinase (TIMP) 1 in patients with juvenile idiopathic arthritis (JIA) and correlated these with different disease variables. Sera of 70 patients with JIA (ILAR 2001 criteria) and 33 age- and sex-matched controls were assayed by enzyme-linked immunosorbent assay. Nonparametric tests were used for analysis of data. The subtype distribution of the JIA patients was: enthesitis-related arthritis (ERA) 24, polyarticular 22, systemic onset 13, oligoarticular 8, and others 3. The median level of RANKL, OPG, pro-MMP1, MMP3, and TIMP-1 were elevated in JIA patients as compared to controls (p < 0.001). There was no difference in levels among different types of JIA. RANKL/OPG ratio was elevated in all subtypes of JIA. MMP3/TIMP-1 ratio correlated with measures of disease activity including swollen and tender joint count, erythrocyte sedimentation rate, and disease activity score (rS 0.28, p < 0.05). Ours is the first study to show elevated RANKL in serum of patients with JIA. Further, our data suggest that patients with ERA have similar levels to other forms of JIA. Association of the MMP3/TIMP-1 ratio with disease activity suggests that it may be a useful biomarker for follow-up.     

骨保护素和骨唾液蛋白在风湿钙化二尖瓣的表达及意义

目的观察骨保护素和骨唾液蛋白在风湿性心脏病(风心病)二尖瓣的表达。方法将手术切除的42枚二尖瓣分为风心病组24枚和非风心病组18枚,采用免疫组化染色观察骨保护素和骨唾液蛋白在两组的表达。结果风心病组的骨保护素(P<0.001)和骨唾液蛋白(P<0.001)均较非风心病组表达增高。结论在风心病瓣膜中,骨保护素和骨唾液蛋白均呈现高表达,表明风心病瓣膜钙化并非简单的钙盐沉积,很可能是成骨样骨形成。     

骨保护素与代谢综合征

骨保护素(OPG)是一种分泌型糖蛋白,属于肿瘤坏死因子受体超家族成员,不仅在骨代谢过程中起重要作用,而且是重要的血管调节因子,能够保护血管内皮细胞,抑制血管钙化和动脉粥样硬化.代谢综合征(MS)包括腹型肥胖、胰岛素抵抗、血脂异常、高血糖、高血压等.MS各组分均为心血管疾病的危险因素,2型糖尿病患者血OPG水平明显升高,但是OPG与MS其他各组分之间的关系日前还存在争议.     

OPG/RANKL/RANK Pathway as a Therapeutic Target in Cancer

Bone metastases play an important role in the morbidity and mortality of patients with malignant disease. Despite therapeutic advances in the treatment of solid organ malignancy such as lung cancer, less development on metastasis interventions has been forthcoming. More recent research has focused on molecular pathway manipulation in the prevention and treatment of metastatic bone disease and associated complications such as bone pain and hypercalcemia. The osteoprotegerin/receptor activator of nuclear factor-кβ ligand/receptor activator of nuclear factor-кβ pathway, which is physiologically involved in bone turnover, has been of considerable interest, and recent promising data have been revealed. In this study, we describe this molecular pathway in terms of its natural physiological function, manipulation for therapeutic benefit, and recent clinical trial results.     

补肾壮骨胶囊含药血清对大鼠成骨细胞增殖及骨保护素mRNA表达的影响

目的:观察补肾壮骨胶囊含药血清对SD大鼠成骨细胞(OB)增殖、骨保护素(OPG)mRNA表达的影响,探讨其防治骨质疏松的机理。方法:将40只3月龄SD雌性大鼠分为补肾壮骨胶囊灌胃组(高、中、低剂量)和空白对照组制备含药血清和空白对照血清;取1天龄SD大鼠颅盖骨,分离、培养成骨细胞(OB),分别加入各实验血清组培养液培养OB,倒置相差显微镜下观察OB生长情况,MTT法测定OB的OD值,RT-PCR检测各组成骨细胞OPGmRNA表达。结果:3-8天时,补肾壮骨胶囊高、中、低含药血清组成骨细胞OD值均高于空白对照组(P<0.05)。各含药血清组成骨细胞OPGmRNA表达均高于空白对照组(P<0.01);补肾壮骨胶囊高、中、低含药血清组间比较,差异无显著意义(P<0.05)。结论:补肾壮骨胶囊含药血清组能促进OB增殖、上调OPGmRNA表达,可能是其防治骨质疏松的机制之一。     

不同浓度葡萄糖对MG63细胞株护骨素和护骨素配体及其相关因子表达的影响

目的：观察不同葡萄糖浓度环境下人成骨肉瘤MG63细胞株护骨素（OPG）、护骨素配体（OPGL）及其相关因子如肿瘤坏死因子相关凋亡诱导配体（TRAIL）、巨噬细胞集落刺激因子（M—CSF）、转化生长因子β（TGF-β）的表达。方法：用RT—PCR法检测基因表达情况。结果：高糖能下调MG63细胞中OPG及TGF—β的表达，上调OPGL、M—CSF和TRAIL的表达。结论：高糖环境可能导致成骨细胞中OPG及TGF—β的表达减少，OPGL、M-CSF和TRAIL等细胞因子的表达增多，使破骨细胞的数目和活性增加，骨吸收增强和骨量丢失，这可能是糖尿病骨质疏松症的一个重要的发病机制。     

米索前列醇对去势后大鼠骨保护素的影响

目的:通过给予去势后大鼠米索前列醇,了解米索前列醇对骨密度及成骨细胞分泌骨保护素 (Osteo protegerin, OPG)的影响。方法:鼠龄90 d的Wistar雌性大鼠共 30 只,分为正常对照组(A组)、去势组(B组)、去势给米索前列醇组(C组),C组去势后第2 d予以2 mg·kg-1·d-1剂量的米索前列醇灌胃,于术后28 d对各组的骨密度进行检测,同时取左侧胫骨干骺端观察骨保护素 mRNA水平的变化。结果: 骨密度检测结果显示 A组最高,C组次之,而B组最低,A组、B组、C组之间差异有显著性(P<0.05);骨保护素3组之间差别有显著性,C组最高,B组次之,A组最低(P<0.05)。结论: 米索前列醇可能通过刺激骨保护素的表达及分泌,来抑制去势后雌性大鼠骨量的丢失。     

RANKL/RANK/OPG系统造成人工关节假体无菌性松动的机制

人工关节假体无菌性松动是影响关节置换术长期疗效的重要因素。许多研究表明,无菌性松动与RANKL/RANK/OPG系统的关系密切。该系统是在破骨细胞分化、激活和凋亡过程中的一个重要信号调节系统,将骨代谢、免疫系统和内分泌系统紧密地联系起来。研究发现,体内多种激素和细胞因子等均直接或间接地调节该系统的表达,调控RANKL、OPG二者之间的平衡,从而介导破骨细胞的分化和功能而达到影响骨代谢的作用。该文就近年RANKL/RANK/OPG系统与人工关节无菌性松动机制的研究进展作一综述。     

Pathogenesis of vascular calcification in dialysis patients

Soft-tissue and vascular calcification are highly prevalent in end-stage renal disease (ESRD). Vascular calcifications manifest as both medial and intimal calcification of arteries and are a hallmark of the accelerated atherosclerosis observed in uremia. The nature of vascular calcification is progressive, and is associated with arterial stiffness and increased cardiovascular mortality. Age, duration of dialysis, and diabetes mellitus are clear determinants of the severity of vascular calcification; however, more recently novel insights into the pathomechanisms of unwanted calcification processes have been gained. Disturbances of mineral metabolism such as hyperphosphatemia and hypercalcemia appear to contribute to progressive calcification, not only by passive precipitation but by actively inducing changes in vascular smooth muscle cell behavior toward an osteoblast-like phenotype. Specific calcium-regulatory proteins may act locally or systemically as calcification inhibitors. Dysregulations of calcification inhibitors, including fetuin-A, matrix Gla protein, osteoprotegerin, and pyrophosphates may also be pathophysiologically relevant factors in the context of uremic extraosseous calcification. In this context, low serum fetuin-A levels were recently found to be associated with increased mortality in cohorts of dialysis patients. This overview intends to summarize current knowledge of the scientific concepts involved in the pathogenesis of extraosseous calcification in ESRD.